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1
Kelsall, Angela. « Respiratory physiology in chronic cough ». Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491479.
Texte intégralRésumé :
Introduction: Varying methods of cough quantification have been used to describe cough frequency, although there is no consensus which method best relates to subjective rating of cough. With increased availability of semi-automated cough recording devices, the capability to carryout anti-tussive studies is greatly increased. However, there is no data available describing the magnitude of change in cough frequency necessary to provide therapeutic benefit. Female patients are over represented in specialist cough clinics. There is little data describing pulmonary function and airway inflammation in phenotyped patients and how these measures may relate to objectively measured cough. Airway inflammation isa common feature of chronic cough, regardless of the trigger for cough. The repetitive mechanical insult of the act of coughing may be responsible for the presence ofthis inflammation. Methods: 100 patients with unexplained chronic cough under went full diagnostic testing in order to determine potential triggers for cough. Procedures included pulmonary function testing; (spirometry, eND, EBC pH, BHR, Cough challenge, induced sputum, objective and subjective cough monitoring), Bronchoscopy, 24 hour impedance monitoring with simultaneous cough monitoring, Gastroscopy and ENT. A subset of cough recordings were quantified in cough sounds, cough seconds and cough epochs to determine the best way to quantify cough. 20 healthy volunteers performed voluntary coughing manoeuvres to determine the acute effects of coughing on airway function and inflammation. Results: Cough sounds and seconds correlate moderately with subjective and QDL . methods. Patients reported a reduced cough frequency whilst undergoing impedance testing; a reduction of33% was seen although patients were unable to quantify the scale of change. Female patients coughed substantially more than male patients, with the largest difference seen at night. Cough frequency was predicted by gender, C5 and age. Cough frequency was not related to a specific trigger for cough. Reduced small airway flows were seen that were independent of BHR. Prominent airway neutrophilia was seen regardless of the trigger for cough. Acute changes in eND and EBC were seen after short periods ofvoluntary coughing. Sputum inflammatory mediator levels showed huge variability and did not change as a result of coughing. Bronchodilation ofthe small airways was also seen after coughing. Conclusion: The use of objective cough monitoring has enabled me for the first time to describe the most appropriate current methods of cough quantification and to demonstrate the magnitude ofreduction in cough frequency that is appreciated by -patients.-I-havereportedimportant significant genderdifferences in cough frequency and shown that cough frequency is predicted not only by gender but also age and cough reflex sensitivity showing important implications for underlying mechanisms of chronic cough. I have also shown for the first time that pulmonary function measures are reduced in patients without indication of asthma. The mechanical act of coughing causes acute bronchodilation of small airways and reduces eND and EBC pH.
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HOIT, JEANNETTE DEE. « AGE AND SPEECH BREATHING (KINEMATICS, PHYSIOLOGY, RESPIRATORY) ». Diss., The University of Arizona, 1986. http://hdl.handle.net/10150/183956.
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The present investigation was designed to elucidate the potential influence of age on speech breathing. Toward this end, 30 men representing three widely different age groups (25, 50, and 75 years) were studied. These individuals were carefully selected to meet stringent criteria, the most important of which related to health and physical characteristics. Speech breathing was studied via anteroposterior diameter changes of the rib cage and abdomen. Recordings were made during extemporaneous speaking and reading and during the performance of various chest wall maneuvers used in the measurement of the speech breathing data. In addition to speech breathing, selected measures of general respiratory function were obtained. These included measures of subdivisions of the lung volume and measures of resting tidal breathing. Results indicated that these 30 subjects were representative of other subjects studied with respect to measures of general respiratory function. Subdivisions of the lung volume were found to differ with age in the manner predicted by previous investigations. Age-related differences were most marked for measures of vital capacity and residual volume. By contrast, there were no age-related differences for measures of resting tidal breathing. Several speech breathing measures were found to differ with age. Age-related differences were usually between the 25- and 75-year-old subject groups and less commonly between the 25- and 50-year-old subject groups. For extemporaneous speaking, differences were found for lung volume excursion, rib cage volume initiation (referenced to the rib cage volume associated with the relaxed configuration of the chest wall), number of syllables per breath group, and lung volume expended per syllable (in percent vital capacity). For reading, differences were found for lung volume expended per syllable (in percent vital capacity). Age-related similarities and differences in general respiratory function and speech breathing are discussed in relation to possible underlying mechanisms. In addition, implications are drawn regarding evaluation and management of individuals with speech breathing disorders.
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Pfitzer, Silke. « The respiratory physiology of opioid immobilisation in African antelope ». Thesis, Pfitzer, Silke (2019) The respiratory physiology of opioid immobilisation in African antelope. PhD thesis, Murdoch University, 2019. https://researchrepository.murdoch.edu.au/id/eprint/54072/.
Texte intégralRésumé :
This thesis addresses the mitigation of opioid-induced respiratory depression in wild African antelope species.
Potent opioids such as etorphine or thiafentanil are often used for the immobilisation of wild herbivores. One disadvantage of using these potent opioids is that they can cause clinically significant respiratory depression which is due to their potent effect on mu-opioid receptors. Activation of mu-opioid receptors in the respiratory centres of animals depresses neurons that generate the normal respiratory rhythm. At the same time activation of mu-opioid receptors on chemo receptors in the brain stem, on the aortic arch and carotid bodies depresses the normal respiratory drive as these chemo receptors become less sensitive to activation by hypercapnia, hypoxaemia and acidaemia. This effect in turn leads to a reduction of the respiratory frequency and tidal volume. Furthermore, pulmonary vasoconstriction, caused by the sympathomimetic actions of etorphine, decreases pulmonary perfusion. This effect leads to impaired diffusion of oxygen through the alveolar membrane. Studies have found that serotonergic ligands, specifically 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), improved blood oxygenation by reducing opioid-induced respiratory depression and improving pulmonary perfusion through their serotonergic effects on the lungs and brain. More specifically, 8-OH-DPAT binds to 5-HT1A and 5-HT7 serotonin receptors in the lungs and brain. This binding results in smooth muscle relaxation and improved pulmonary perfusion without affecting catatonia and sedation caused by opioids. It was thought that the use of the R-enantiomer of 8-OH-DPAT (R-8-OH-DPAT) in comparison to the racemic form (RS-8-OH-DPAT), might produce even better results because of its high specificity at the 5- HT1A receptors.
Although some literature on the pharmacokinetic data of 8-OH-DPAT in rats and marmosets existed, there was no published literature available on the pharmacokinetics of 8-OH-DPAT in ungulates.
Therefore, the investigation into the pharmacokinetics and bioavailability of R-8-OH-DPAT in goats served as the first step in a series of experiments to understand the viability of adding R-8-OH-DPAT to an opioid-based immobilisation protocol for wild antelope species in order to alleviate respiratory depression. It was hypothesised that the pharmacokinetics and bioavailability of R-8-OH-DPAT in goats would be similar but different to that reported in other species. It was established that the bioavailability of R-8-OH-DPAT when injected intramuscularly (IM) into goats was 66%. At the dosage used in this experiment (0.1 mg kg- 1), signs of serotonin toxicity were observed in some of the goats. The bioavailability results, as well as the encountered side effects in goats, guided the choice of three experimental R-8- OH-DPAT dosages for the next experiment.
The second experiment aimed to determine the ability of R-8-OH-DPAT, when administered in combination with etorphine in a dart, to prevent opioid-induced respiratory depression in blesbok (Damaliscus pygargus phillipsi) and impala (Aepyceros melampus). The experiment also aimed to establish the most clinically effective dosage of R-8-OH-DPAT, in these species.
Blesbok and impala were chosen for the second experiment as they were abundant and readily available in the study area. Both are antelope species commonly immobilised with potent opioids. Impala are regularly used in immobilisation experiments. It was hypothesised that R-8-OH-DPAT would mitigate opioid-induced respiratory depression in wild ungulates without affecting the quality of immobilisation. R-8-OH-DPAT did not influence induction, immobilisation or recovery scores in either of the species. However, this experiment revealed that there were substantial differences between the two antelope species and their physiological changes after the administration of etorphine alone as well as etorphine in combination with 0.005, 0.02 and 0.07 mg kg-1 R-8-OH-DPAT respectively. Surprisingly, opioid-induced hypoxia was substantially more severe in impala compared to blesbok. Respiratory rate in blesbok, but not impala, increased with an increasing dosage of R-8-OHDPAT but this did not translate into clinically relevant improvements in partial arterial oxygen pressure (PaO2) values in blesbok.
In impala, the medium and higher dosages of R-8-OH-DPAT combined with etorphine led to an improved PaO2 and decreased opioid-induced tachycardia during the first ten minutes of immobilisation.
It was concluded that species-specific effects and the possibility of serotonin toxicity at higher dosages, which seemed most effective, might not allow the routine use of R-8-OHDPAT at appropriate dosages for wildlife immobilisation.
These results lead to the third experiment which aimed at comparing physiological effects of two commonly used potent opioids, namely etorphine and thiafentanil, in both antelope species. It was hypothesised that the time to recumbence, immobilisation quality and physiological variables during immobilisation of blesbok and impala respectively would differ between the two potent opioids.
The results of this experiment demonstrate that both opioids used in high dosages are suitable for immobilisation of blesbok and impala without the addition of any sedative or tranquillisers. Both, blesbok and impala developed hypertension with either of the opioids. The thiafentanil treated animals of both species developed higher systemic blood pressure compared to the etorphine treated animals. The healthy animals used for these experiments recovered from hypertension without apparent adverse consequences.
Thiafentanil in impala achieved a faster time to recumbence compared to etorphine but thiafentanil also was responsible for more incidences of prolonged apnoea during the beginning of the monitoring period in impala. Overall, there were large differences in the reaction of individual impalas to the opioid immobilisation, which seemed to result in unpredictable immobilisation.
In blesbok, opioid-induced respiratory depression, hypoxia and hypercapnia were much less pronounced than in impala. Thiafentanil treated blesbok had higher respiratory rates, higher PaO2 and lower partial arterial carbon dioxide pressure (PaCO2) compared to etorphine treated blesbok. There was no difference in time to recumbence between the two opioids in blesbok.
In conclusion, for short term management procedures of impala and blesbok, both opioids are suitable. No matter which opioid is used, both cause hypoxaemia to a greater or lesser degree and oxygen supplementation should be considered for both species.
Veterinarians should also be aware that in some species, such as impala, thiafentanil can achieve a faster time to recumbence than etorphine. However, this statement cannot be applied across all species as in blesbok there was no significant difference between both drugs with regards to time to recumbence. In addition, time to recumbence has to be weighed against potential negative respiratory, pulmonary and cardiovascular side-effects of the drug.
While these experiments did not give the desired positive results with regards to the use of R-8-OH-DPAT to alleviate opioid-induced respiratory depression, they led to insights into differences between the two opioids which will enable veterinarians to make a more educated decision as to which opioid should be used preferentially.
New insights into the differences between blesbok and impala with respect to reaction and physiological changes caused by opioids will also enable researchers to make decisions with regards to species selection for wildlife trials. It may also explain some of the difficulties encountered when immobilising impala.
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Hallifax, Robert. « Understanding pneumothorax : epidemiology, physiology and predicting outcome ». Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:6090cef1-318a-4220-970e-2d5b6e3edfac.
Texte intégralRésumé :
Contrary to traditional teaching, patients with Primary Spontaneous Pneumothorax (PSP) do not have normal lungs. Emphysema-like change (ELC) and inflammation are common. However, the natural history of ELC and its significance in terms of future disease is not known. Current management of pneumothorax is generic and not personalised. This thesis updates the UK epidemiology of pneumothorax, describes the use of two novel methods to examine the lungs, a method of predicting early treatment failure, the association of CT findings and recurrence, and a systematic review of chemical pleurodesis to reduce recurrence. Analysis of fifty years' data on ~150,000 admissions demonstrated that the incidence of pneumothorax is increasing, and established a method to identify primary from secondary pneumothoraces and their relative risk of recurrence. Reduced ventilation of hyperpolarised Xenon on enhanced-Magnetic Resonance Imaging (MRI) was seen in those PSP patients with greater low attenuation areas on Computed Tomography (CT) and with reduced pulmonary function. A model of lung inhomogeneity found that metrics of lung ventilation distinguished pneumothorax patients from healthy volunteers and Chronic Obstructive Pulmonary Disease (COPD) patients. This may represent subtle or mild disease, not identified on standard testing, which may be exacerbated by smoking. CT scanning found that mild emphysema and cystic airspaces were common in PSP patients. Ex- or current smokers had more (and larger) cysts. Emphysema was more common in smokers and patients with a history of previous pneumothorax: who were at higher risk of recurrence. However, variation in number and size of cysts were seen in both those patients with and without recurrence. As such, no single algorithm to predict recurrence was identified. Airflow measurement early in the patient pathway has the potential to identify those likely to fail treatment, potentially allowing early triage to surgery. The addition of talc or minocycline as an adjunct to surgery provides the lowest recurrence rates, but physician-led talc poudrage may be similarly effective. Those in whom surgery is not suitable, chemical pleurodesis could be offered via chest drain. Data presented in this thesis thus provides insights into the underlying abnormalities in PSP and lays the groundwork for strategies to fundamentally alter the management paradigm.
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Whiteley, Jonathan. « Biomathematical models for some respiratory forcing techniques ». Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288052.
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Hlongwana, Simangele I. « Investigating adherence of authorised prescribers to standerd treatment guidelines/essential medicine list when treating children presenting with respiratory conditions at primary health care level in the umkhanyakude health district, Kwazulu Nata ». Thesis, University of Limpopo (Medunsa Campus), 2013. http://hdl.handle.net/10386/1076.
Texte intégralRésumé :
Thesis (MSc(Med)(Pharmacy) ) -- University of Limpopo, 2013.Introduction: Primary Health Care (PHC) is regarded as the first level of contact with the National Health System with health care services provided mainly by nurses with varying competences. PHC is about interaction with people thus the quality of PHC depends extensively on the competence of the people who provide it. Therefore, the way health care personnel are trained and how capacity continues to be developed is of fundamental importance to PHC. Following the Alma-Ala Declaration, policies, such as the National Drug Policy (NDP) were developed in South Africa to guide health care services. The NDP resulted in the formulation of Standard Treatment Guidelines/Essential Medicine List (STGs/EML). Emphasis has been placed on all prescribers to strictly adhere to these guidelines when providing clinical patient care. Despite these developments reports still indicate that antibiotics are irrationally used when treating respiratory infections. It is therefore imperative that localised reasons for deviations from the STGs/EML when treating respiratory conditions are thoroughly investigated to facilitate relevant interventions. Objectives: The objectives of the study were to: (1) document the treatment prescribed to children up to 12 years of age for respiratory conditions, (2) assess adherence of the authorised prescribers to the 2008 PHC STGs/ EML and (3) determine factors impacting on deviations from the 2008 STGs/EML. Method: Twenty randomly selected PHC facilities in the district participated in the study. In each of the 20 selected PHC facilities, three prescribers were randomly selected for the structured interview and auditing of their prescription registers. Five prescriptions from each of the sampled prescription registers of the selected authorised prescribers, containing any of the children's respiratory conditions to be studied, were audited. A total of 15 prescriptions from each of the selected PHC facilities were audited. Descriptive statistics was used to xii analyse data and responses to categorical variables were summarised as frequency counts and percentages. Results were presented as tables, figures and graphs. Results: Pneumonia (39.7%) was found to be the most common respiratory condition seen at Umkhanyakude Health District followed by the common cold and influenza. Amoxicillin (52%) was the most often prescribed antibiotic for these respiratory conditions. Only 4% of prescribers showed full adherence to the 2008 PHC STGs/EML. While prescribers had a positive attitude towards the 2008 PHC STGs/EML, their sense of adherence, content understanding of these guidelines, as well as knowledge of medicine used for respiratory conditions, were exaggerated. Failure to accurately diagnose respiratory conditions and lack of implementation and monitoring strategies were also amongst the factors impacting on adherence. Conclusion: Adherence to the 2008 PHC STGs/EML for the treatment of respiratory conditions in children up to 12 years of age was found to be a challenge in Umkhanyakude PHC facilities with only four percent of prescribers adhering to these guidelines. The Umkhanyakude Health District Management team must consider employing multifaceted interventions from the recommendations of this study in order to improve adherence to the PHC STGs/EML. Recommendations: Strategies such as intensified monitoring and evaluation, improved supervision, targeted training and education together with compulsory in-service training are recommended to improve adherence to the STGs/EML in the Umkhanyakude Health District. Guideline implementation strategies with integrated approaches to guideline dissemination must also be strengthened.
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Davidson, Glen William. « The respiratory physiology of the New Zealand paddle crab, Ovalipes catharus ». Thesis, University of Canterbury. Zoology, 1994. http://hdl.handle.net/10092/5535.
Texte intégralRésumé :
Ovalipes catharus is a back-burrowing brachyuran which makes temporary burrows in soft sandy sediments. Like many burrowing crabs, O. catharus shows prolonged periods of sustained reverse ventilation. Well settled individuals were found to exclusively reverse-ventilate, regardless of burial state. However following activity, both buried and unburied animals showed periods of forward ventilation. Immediately following 15 minutes of exercise by swimming, crabs remaining unburied spent an average of 75.4 ± 14.2% of the time forward ventilating, while crabs that were allowed to burrow in sand spent only 32.5 ± 12.1% of the time in the forward mode.
Previous studies suggest that buried crabs reverse the direction of ventilation in order to maintain a respiratory water stream by utilising super incumbent water. (Garstang, 1897b; Hartnoll, 1972; Taylor, 1984; McLay and Osborne, 1985; Otwell and Webb, 1990). Caine (1974) went further to suggest that interstitial oxygen tensions may be too low to sustain the oxygen demands of buried crabs. In laboratory studies the interstitial water in sediments inhabited by O. catharus, indeed, were found to be hypoxic. Values of interstitial Po2 were as low as 50% of that of the super incumbent water. Despite this, the present study has shown that both forward and reverse ventilation are utilised by
O. catharus, regardless of burial state. When buried, Pio2 is maintained at near normoxic levels during forward ventilation by the utilisation of super incumbent water for ventilation. This is enabled by the formation and use of exostegal channels which provide a conduit for water flow from above the sediment to the primary inhalent openings, the Milne-Edwards apertures.
In unburied O. catharus, branchial water flow patterns were found to be as described for other species (Hughes et al., 1969; McDonald et al., 1977). Water is drawn into the ventral hypobranchial space of the branchial chambers at the bases of the limbs and flows dorsally through the gills to the epibranchial space before passing anteriorly and being exhaled via ducts near the mouthparts. This flow is roughly countercurrent to the direction of haemolymph flow within the gills. When the direction of ventilation was reversed, this pattern of flow was disrupted. Anteriorly, water enters the prebranchial chambers, where the scaphognathites are situated before passing into the epibranchial space. Much of this water flows posteriorly and is exhaled via apertures between the fourth and fifth pereiopods. Some exhalent flow appears at the Milne-Edwards apertures suggesting some concurrent exchange may be possible. From the major sites of inhalation, the patterns of flow appear to be similar in buried crabs. However, the proportions of flow exiting each aperture were highly variable, suggesting an ability to regulate patterns of gill irrigation in this species.
In unburied crabs, the mean oxygen extraction efficiency was significantly lower and the mean convection requirement (Vw/Mo2) was significantly higher during periods of reverse ventilation (Ew% = 23.7 ± 1.8%; Vw/Mo2 = 18.4 ± 1.7 ml µmol-1) when compared to adjacent periods of forward ventilation (Ew% = 32.9 ± 4.1%; Vw/Mo2 = 13.9 ± 1.9 ml µmol-1). In contrast, in buried crabs, values of Ew% and Vw/Mo2 were similar during adjacent periods of forward (Ew% = 53.3 ± 4.6%; Vw/Mo2 = 10.5 ± 1.4 ml µmol-1 ) and reverse ventilation (Ew% = 49.4 ± 2.9%; Vw/Mo2 = 9.7 ± 0.5 ml µmol-1). The lower values of Ew% and higher values of Vw/Mo2 recorded from unburied reverse ventilating crabs are presumably due to disruption of the counter current gill perfusion/irrigation relationship that exists when ventilating in forward mode. When buried, the improved efficiency of oxygen extraction and convection requirements seen during periods of reverse ventilation compared to unburied crabs utilising this mode, may be due to better irrigation of the gills resulting from regulation of the branchial water flow pathways, or to utilisation of an alternative site for gas exchange. The potential of the branchiostegal lining of the branchial chambers to fulfil such a role was examined. From vascular corrosion casts it was apparent that this region is well supplied with venous haemolymph which returns to the pericardium without being reoxygenated at the gills. This would create a large Po2 gradient across the cuticle of the branchiostegite which is relatively thin (10-20 µm), thus diffusion of oxygen across this barrier and into the haemolymph may be possible. Possible mechanisms of regulation of perfusion of the gills and branchiostegites are discussed.
In unburied crabs, branchial chamber pressure (Pbranch) was similar in magnitude, but of opposite sign, in the two ventilatory modes. In buried animals, values of Pbranch were much greater than those recorded from unburied crabs, and Pbranch was significantly greater during periods of forward ventilation than reverse ventilation. The increased values of Pbranch in buried crabs indicate a greater resistance to ventilatory water flow, especially when ventilating in the forward direction. This increase in ventilatory resistance affected scaphognathite function in two main ways: Firstly, mean scaphognathite stroke volume (Vs) in buried crabs was reduced compared to unburied animals. In forward and reverse ventilating unburied animals, mean Vs was similar at 4.86 ± 0.14 ml beat-1kg-1 and 4.92 ± 0.15 ml beat-1kg-1, respectively, while in buried crabs, mean values of Vs were 3.63 ± 0.14 ml beat-1kg-1 and 4.11 ± 0.14 ml beat-1kg-1 in forward and reverse ventilation, respectively. Secondly, as a result of the higher values of Pbranch recorded from buried animals, ventilatory stroke work (Ws) and ventilatory power (Wr) were increased when buried, especially when utilising the forward mode.
By converting ventilatory power terms to oxygen equivalents and using efficiency values from the literature (Wilkens et al., 1984), estimates of the energetic cost of ventilation (ie. the fraction of total Mo2 that is devoted to ventilation) were calculated for the four treatment groups at a given ventilatory flow (Vw = 0.6 1 kg-1 min-1). In unburied animals, the ventilatory power and oxygen requirements were
similar in the two modes. However, as a result of the lower values of Ew% and Vw/Mo2 recorded during reverse ventilation, Mo2 was lower at a given Vw in this mode. Because of this, a higher proportion of total Mo2 (23.6%) was required for ventilation in the reverse mode, than the forward mode (12.1%).
In buried crabs, Ew%, Vw/Mo2 and Mo2 were all similar at a given Vw. However, the increased ventilatory resistance seen in the forward mode, required an increased power output from the ventilatory muscles when generating flow, compared to that during reverse ventilation. This translates into an increased oxygen requirement of the ventilatory musculature. As a result, the estimated ventilator fraction during forward ventilation was higher (43.3%) than during reverse ventilation
(20.0%).
The predominant modes of ventilation in buried and unburied crabs following exercise reflect these differences. Unburied crabs primarily utilise forward ventilation while buried crabs utilise reverse ventilation. It is suggested that O.catharus modify their ventilatory behaviour depending on environmental factors and the internal physiological state of the animal, in order to reduce the overall energetic cost of ventilation. Potential mechanisms of control of ventilatory switching are discussed.
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Rogers, Nicholas John. « The respiratory and gut physiology of fish : responses to environmental change ». Thesis, University of Exeter, 2015. http://hdl.handle.net/10871/19295.
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Many of the habitats occupied by fish are highly dynamic, naturally demonstrating substantial abiotic fluctuations over diurnal, tidal or seasonal cycles. It is also the case that throughout their 545 million year evolutionary history, fish have existed in aquatic environments very different to those of the present day. However, the past several decades have seen unprecedented rates of environmental change, at local and global scales, arising from human activities. The two major themes of the present thesis are: 1) Respiratory responses of fish to changes in environmental oxygen and temperature in the context of exploring intra- and inter-specific trait variation and its ecological implications 2) The effects of environmental factors (oxygen, carbon dioxide, temperature and seawater chemistry) on the intestinal precipitation and excretion of calcium carbonate by marine teleosts. In the first study (chapter two) a comprehensive database of fish critical PO2 (Pcrit) data compiled from the published literature is presented. The systematic review of this literature provided the opportunity to critically examine methodologies for determining Pcrit as well as its usefulness as an indicator of hypoxia tolerance in fish. The second study (chapter three) examines whether inter- and intra-specific variation in thermal and hypoxia tolerance in two reef snapper species (Lutjanus carponotatus and Lutjanus adetii) reflects their distributions across the contrasting biophysical environments of the reef flat and reef slope surrounding Heron Island on the Great Barrier Reef. L. carponotatus was clearly the most thermally and hypoxia tolerant of the two species, demonstrating a ~3.5 °C wider thermal tolerance zone (higher CTmax, lower CTmin) and ~26% lower Pcrit than L. adetii. These results suggest that the contrasting distribution of these species between flat and slope reef zones is reflected in their physiological tolerances. However, there was no evidence of intra-species variation in tolerance between flat and slope caught L. carponotatus individuals, indicating that this species does not form physiologically distinct subpopulations between these reef zones. The third study (chapter four) experimentally quantified the effect of hypercarbia (3000 μatm) and hypoxia (50% air saturation) on gut carbonate production by the European flounder (Platichthys flesus). Both hypercarbia and hypoxia resulted in a significant increase in carbonate excretion rate (1.5-fold and 2.4-fold, respectively) and acted synergistically when combined. In the final study (chapter five), gut carbonate production was measured in the European flounder undergoing conditions simulating the ‘calcite seas’ of the Cretaceous. The results of this study support the hypothesis that ocean conditions prevalent during the Cretaceous period resulted in piscine carbonate production rates substantially higher (~14-fold) than the present day. Ultimately, this thesis directly links the environmental physiology of fish at the individual level to wider scale implications (past, present and future), ranging from local ecological patterns all the way up to global carbon cycles.
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Santin, Joseph M. « Context-dependence of physiological systems : environment-physiology interactions in the respiratory control system ». Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright149336916471128.
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Vulesevic, Branka. « Respiratory plasticity in the zebrafish (Danio rerio ) ». Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/27070.
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The aim of this thesis was to investigate respiratory plasticity in zebrafish (Danio rerio) confronted with long-term changes in water gas composition (hypoxia, hyperoxia or hypercapnia) either as embryos or adults. The ventilatory responses to acute changes in water gas composition (hypoxia, hypercapnia or cyanide) were assessed using a non-invasive technique (Altimiras and Larsen, 2000) to continuously monitor breathing frequency (f R) and relative breathing amplitude. The ventilatory response to acute hypoxia consisted of an increase in fR while the response to acute hypercapnia was an increase in relative breathing amplitude. (Abstract shortened by UMI.)
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Harris, Roger Mark. « A study of the respiratory physiology of the subtidal bivalve Venus casina ». Thesis, University of Liverpool, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305027.
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Yan, Sheng. « Evaluation of human respiratory muscle fatigue ». Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41180.
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The first part of my work evaluates bilateral supramaximal transcutaneous phrenic nerve stimulation as a diagnostic test for respiratory muscle fatigue. I found that twitch transdiaphragmatic pressure (Pdi,T) was inversely and linearly related to lung volume (V$ sb{ rm L}$) both before and after fatigue. Although fatigue caused significant decrease in Pdi,T amplitude at all V$ sb{ rm L}$, the fractional decrease in Pdi,T was greater at high V$ sb{ rm L}$, indicating the importance of V$ sb{ rm L}$ as an independent variable that needs to be controlled whenever Pdi,T is determined. Twitch mouth pressure (Pm,T) was found to be linearly related to twitch esophageal pressure (Pes,T), to Pdi,T, and to V$ sb{ rm L}$. All these relationships were reproducible. Diaphragmatic fatigue resulted in significant decrease in Pm,T proportional to the decrease in Pdi,T for a given V$ sb{ rm L}$ so that Pm,T-Pes,T and Pm,T-Pdi,T relationships were unchanged. Thus the Pm,T-V$ sb{ rm L}$ relationship can be used to assess diaphragmatic fatigue non-invasively. Paired phrenic nerve shocks which were well tolerated by normal subjects can be used to obtain a measure of the pressure-frequency curves of the diaphragm, which were reproducible. In particular, I showed that the pressure ratio of diaphragmatic twitch elicited by the second shock at 10Hz over that at 100Hz (T2$ sb{10/100}$) is a valuable index of low frequency fatigue.In the second part of my work I studied the effect of respiratory muscle fatigue on ventilatory response to CO$ sb2$ and respiratory muscle recruitment. The data showed that ventilatory response and respiratory muscle recruitment patterns were different in a number of aspects between diaphragmatic fatigue and global inspiratory muscle fatigue. After diaphragmatic fatigue, the only change was an increase in the recruitment of rib cage muscles, which fully compensated for decreased diaphragmatic contractility because all the ventilatory parameters were constant. After global fatigue, both the diaphragm and rib cage muscles contributed less to breathing but expiratory muscles were recruited resulting in a decrease in end-expiratory P$ sb{ rm L}$ and an increased contribution of elastic energy stored within the respiratory system to inspiratory tidal volume generation. In spite of this, rapid shallow breathing developed while minute ventilation remained constant. These data suggest that the ventilatory control system can detect fatigue and has sufficient plasticity to alter inspiratory drive appropriately. The overall ventilation level can thus be maintained.
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Rahman, Mohammad Atiar. « Ethnicity, gender and cardio-respiratory function ». Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253065.
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Nilsson, Lena. « Respiratory monitoring using reflection mode photoplethysmography : clinical and physiological aspects / ». Linköping : Dept. of Medicine and Care, Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med898s.pdf.
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Howard, Luke Sebastian Geoffrey Eliot. « The effects of prolonged hypoxia on respiration in man ». Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282330.
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Cummin, Andrew R. C. « Some aspects of the ventilatory response to carbon dioxide in man ». Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235853.
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Collier, Clare Georgina. « Factors affecting lung clearance kinetics ». Thesis, Open University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253714.
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Svantesson, Cecilia. « Respiratory mechanics during mechanical ventilation in health and in disease ». Lund : Dept. of Clinical Psychology, Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/38987113.html.
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Scott, Adrienne S. « Comparison of respiratory sinus arrhythmia integration in athletes and non-athletes ». Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33924.
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A comparison of heart rate viability and respiratory sinus arrhythmia (RSA) characteristics was performed in 20 athletes and 12 age-matched sedentary controls (CTRL) (22 +/- 2.4 yrs). More specifically, this study examined the role of regular physical activity on the breathing frequency (BF)---RSA amplitude response curve comparing varsity swimmers (SW) to endurance runners (RU) to test the hypothesis that a locomotor-respiratory entrainment resulting from the water-immersion breathing pattern of swimmers would alter their respiratory related cardiac vagal integrative response. Spectral power components of HRV were computed from R-R interval sequences. Five-minute recordings were performed with subjects breathing either at their spontaneous breathing rate, at four breathing cycles less (M4) and four cycles more (P4) than spontaneous. Amplitude and phase of RSA were computed from the sinusoid fitted to the instantaneous heart rate within each breath while the gain of the RSA response was obtained from the slope of the RSA amplitude versus BF. (Abstract shortened by UMI.)
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Werr, Joachim. « Functions of integrin receptors in extravascular neutrophil migration and respiratory burst / ». Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4337-0/.
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Bachoo, Manjit. « Central mechanisms responsible for generating respiratory-modulated sympathetic nerve discharge ». Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75943.
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The experimental work presented in this thesis explores, in anaesthetized and mid-collicular decerebrate, unanesthetized, cats, the properties of two components of the discharge of sympathetic nerves which are time-locked to the central respiratory cycle and are presumably generated within the central nervous system. One is the inspiration-synchronous burst, the other is a previously unknown late-expiratory burst. The properties of the inspiration-synchronous burst and its temporal relation to the phrenic nerve burst were studied under conditions in which the frequency of the latter was changed over a wide range by superior laryngeal nerve stimulation, by changes in ventilation frequency while the phrenic nerve burst was locked to the pump, and by hypocapnic hyperthermia. The data obtained are consistent with the hypothesis of a common rhythmic driver for phrenic motoneurons and sympathetic preganglionic neurons. Stimulation of low-threshold afferents in the superior laryngeal nerve selectively suppressed the phrenic burst together with the inspiration-synchronous sympathetic discharge and produced vasodilatation. The contribution of the inspiration-synchronous sympathetic discharge to neurogenic vasoconstriction was estimated, in the hindlimb of the cat, from the magnitude of the vasodilatation. A late-expiratory burst of sympathetic discharge was produced by systemic hypercapnia and by raising end-expiratory pressure to between 2 and 7 cmH$ sb2$O. Circumstantial evidence suggests this late-expiratory burst is due to input from late-expiratory neurons to sympathetic preganglionic neurons. As a background to the experimental data a survey is presented of present knowledge of the mechanisms providing mechanical and neural coupling between respiration and circulation. The functional significance of respiratory modulation of sympathetic activity is discussed.
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Kennedy, Ashleigh. « An investigation of the effects of fentanyl on respiratory control ». Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/5998/.
Texte intégralRésumé :
Respiration is a complex rhythmic motor behaviour that metabolically supports all physiological processes in the body and is continuous throughout the life of mammals. A failure to generate a respiratory rhythm can be fatal. Understanding how the respiratory rhythm is generated by the brainstem presents a substantial challenge within the field of respiratory neurobiology. Studies utilising in vitro and in vivo rodent models have provided compelling evidence that a small bilateral region of the ventrolateral medulla, known as the preBötzinger complex (preBötC), is the site for respiratory rhythmogenesis. There is also evidence to suggest a second distinct neuronal group, the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), plays a specialised role in respiratory rhythm generation in the neonatal rodent. During early life in rodents and humans, the respiratory system is immature and an irregular breathing pattern is generated, making this period of life potentially vulnerable to external perturbations. However a step in maturity occurs early in life after which breathing becomes regular. Currently, the underlying mechanisms involved in respiratory rhythm generation during early life are not fully understood. It is hypothesised that the RTN/pFRG functions as the dominant respiratory rhythm generating oscillator during early life when the respiratory system is immature, after which the preBötC becomes the dominant rhythm generator. However, how the preBötC and the RTN/pFRG interact in vivo to produce rhythmic breathing during postnatal development remains elusive. The first aim of this thesis was to assess postnatal maturation of breathing patterns in the mouse using non-invasive whole body plethysmography. Between postnatal day (P) 2 and P3, a critical maturation step occurred, whereby breathing transitioned from an unstable and dysrhythmic pattern to a regular and robust pattern. The second aim of the thesis was to investigate the influence of this postnatal maturation on central respiratory control. Mu (μ) opioid receptor agonists are known respiratory depressants. The activity of the preBötC is depressed by μ opioids in vitro. Furthermore, fentanyl, a potent μ opioid receptor agonist, evokes respiratory frequency depression in vivo by exclusively targeting and depressing preBötC neurons. Conversely, the RTN/pFRG is insensitive to μ opioids. Accordingly, fentanyl was utilised as a pharmacological tool to selectively perturb the preBötC in vivo throughout postnatal development and through to early adulthood. The acute respiratory depressive effects of fentanyl were measured in order to investigate the level of involvement of the preBötC in respiratory rhythm generation throughout this critical developmental time period. Based on the general hypothesis that the preBötC functions as the dominant respiratory rhythm generator when the respiratory system has matured, it was hypothesised that mice would be more susceptible to the respiratory depressive effects of fentanyl after the maturation step has occurred i.e. the respiratory sensitivity to fentanyl would be age-dependent. Initially, mice were repeatedly exposed to fentanyl throughout postnatal development. However, fentanyl failed to induce a respiratory depression at all postnatal ages, suggesting repeated exposure had induced a rapid desensitisation to fentanyl’s respiratory effects. The study design was consequently altered to allow the hypothesis to be sufficiently tested, whereby different mice were studied on each postnatal day i.e. each mouse was only exposed to fentanyl once. This study revealed a trend towards an age-dependent increase in respiratory sensitivity to fentanyl, where mice displayed a heightened respiratory frequency depression in response to fentanyl after the maturation step had occurred from P3 onwards. This data therefore lends support to the hypothesis that the preBötC functions as the dominant respiratory rhythm generator post-maturation. In the clinical setting fentanyl is widely utilised for treating chronic and acute pain. However, despite the potent respiratory depressive actions of fentanyl, the long-term respiratory consequences of repeated exposure remain unexplored both clinically and pre-clinically. Owing to the immaturity of the respiratory system and the corresponding fragile nature of breathing patterns during neonatal life in mammals, a further aim of the thesis was to determine the long-term effects of fentanyl exposure during this vulnerable respiratory time period in the mouse. To establish if the postnatal age of fentanyl-exposure influences long-term respiratory effects, fentanyl exposure during juvenile life, which is regarded as being post-respiratory maturation, was also assessed. Neonatal mice were exposed to fentanyl (0.04 mg/kg daily) from P1-P5 and juvenile mice were exposed from P9-P13. When mice reached adulthood, baseline respiratory activity and the respiratory response to a subsequent fentanyl challenge were assessed during wakefulness and under anaesthesia. When awake, neonatal-exposed mice exhibited a reduced baseline respiratory frequency and an attenuated respiratory sensitivity to fentanyl. Under anaesthesia, neonatal-exposed mice displayed a depressed baseline minute ventilation and a high frequency of spontaneous augmented breaths. In direct contrast to the wakeful state, when anaesthetised, neonatal-exposed mice exhibited a striking hypersensitivity to the acute respiratory depressive actions of fentanyl. In all neonatal-exposed mice, fentanyl evoked a respiratory failure. In juvenile-exposed mice, baseline respiratory activity remained unaltered in the wakeful state and fentanyl also failed to induce a respiratory depression. When anaesthetised, baseline minute ventilation remained unchanged and the high occurrence of augmented breaths exhibited by the neonatal-exposed mice was not observed. Unlike the wakeful state, fentanyl evoked a depression of respiratory activity in the juvenile-exposed mice when anaesthetised, however the augmented sensitivity to fentanyl and consequential respiratory arrest displayed by the neonatal-exposed was not observed. This data indicates that the anaesthetised state is more susceptible to respiratory depression. Furthermore, the data suggests that neonatal life represents a time period that is particularly vulnerable to the respiratory effects of opioid depression. The final aim of the thesis was to determine the long-term effects of neonatal fentanyl exposure on neurokinin-1 (NK1R) and μ opioid receptor expression within the ventral respiratory column (VRC), a region of the ventrolateral medulla comprising the preBötC. Neonatal-exposed mice exhibited significantly less NK1R and μ opioid receptor expressing cells in the region of the preBötC. This data suggests that repeated fentanyl exposure in neonatal life induces a long-term downregulation of these receptors. In conclusion, fentanyl’s acute respiratory effects were age-dependent, which lends supports to the hypothesis that the preBötC functions as the dominant rhythm generator post-maturation. Furthermore, this thesis highlights the vulnerabilities of neonatal life to the lasting effects of opioid respiratory depression, whilst also providing invaluable insight into state-dependent respiratory modulation and depression.
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Lewis, John E. « Dynamics of neural networks and respiratory rhythm generation ». Thesis, McGill University, 1991. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=60568.
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The phase resetting effects of stimulating the superior laryngeal nerve at different phases of the respiratory cycle in cats were measured in terms of the latency of onset of the cycle following stimulation. Fixed-delay stimulation was also used; for certain combinations of delay, stimulus intensity, and cycles between stimuli, it resulted in (1) a variable, rather than consistent, response, and (2) a transient increase in cycle duration during and after stimulation. Phase resetting and fixed-delay stimulation of a simple three-phase model for neural rhythm generation produce responses that are qualitatively similar to those obtained experimentally.We consider the dynamical properties of a class of theoretical models of neural networks that have the same mathematical formulation as the above three-phase model, but consist of a larger number of randomly connected elements. A simple transformation of these models shows correspondence with previous neural network models and enables a theoretical analysis of steady states and cycles. Complex aperiodic dynamics are found in networks consisting of 6 or more elements.
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Bierbower, Sonya M. « ENVIRONMENTAL EFFECTS ON BEHAVIOR AND PHYSIOLOGY IN CRAYFISH ». UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/778.
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Despite dramatic morphological differences between animals from different taxa, several important features in organization and sensory system processing are similar across animals. Because of this similarity, a number of different organisms including mammals, insects, and decapod crustaceans serve as valuable model systems for understanding general principles of environmental effects. This research examines intrinsic and extrinsic factors by behaviorally and physiologically means to identify the impact of environmental conditions on two distinct crayfish species- Procambarus clarkii (surface) and Orconectes australis packardi (cave).
The research identified behavioral and physiological responses in these two morphological and genetically distinct species. The studies also examined multiple levels of complexity including social behavior, an autonomic response, chemosensory capabilities and neuronal communication, identified comparative similarities/differences, addressed learning and environmental influences on learning and examined behavioral and cellular responses to high levels of carbon dioxide. I found environmental factors directly influence crayfish behavior of social interactions. Interactions were more aggressive, more intense and more likely to end with a physical confrontation when they took place 'in water' than 'out of water'. The modified social interaction resulted in a altered fighting strategy.
A study on motor task learning was undertaken which showed similar learning trends among these crayfish species despite their reliance on different sensory modalities. I also demonstrated learning was dependent on perceived stress by the organism. Previously trained crayfish inhibited from completing a task showed significant increase in an autonomic stress response.
Studies on the behavioral and physiological responses to CO2 revealed that high [CO2] is a repellent in a concentration dependent manner. The autonomic responses in heart rate and an escape tailflip reflex shows complete cessation with high [CO2]. A mechanistic effect of CO2 is by blocking glutamate receptors at the neuromuscular junction and through inhibition of the motor nerve within the CNS.
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Scott, Graham. « Evolution of respiratory physiology for extreme high-altitude flight in the bar-headed goose ». Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/13075.
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Bar-headed geese migrate over the Himalayas at up to 9000m elevation where they must sustain the high metabolic rates needed for flight despite being severely hypoxic. The present thesis studied the respiratory physiology of this species to better understand the basis for this impressive feat. Evolutionary changes important for high altitude flight were deduced by comparing bar-headed geese to several low altitude species (greylag geese, pink-footed geese, barnacle geese, mallard ducks, or pekin ducks).
Theoretical modelling of the O2 transport pathway was first used to determine traits with the greatest influence over O2 transport in hypoxia. This suggested that a heightened capacity to increase ventilation, a high haemoglobin O2 affinity, and an enhanced O2 diffusing capacity in the muscle should be most influential for enhancing O2 supply. Therefore, the remainder of this thesis tested the general hypothesis that these traits have evolved in bar-headed geese.
Total ventilation was higher in bar-headed geese than in low altitude waterfowl during severe environmental hypoxia. This was entirely due to larger tidal volumes, which should have further enhanced effective ventilation of the gas exchange surface and thus increased O2 loading and arterial O2 tension. Two primary mechanisms accounted for this difference, (i) a reduction in metabolic depression during hypoxia and (ii) a blunted chemosensitivity to respiratory hypocapnia. These studies also supported previous research showing that bar-headed geese have a higher haemoglobin O2 affinity.
Oxygen diffusing capacity in the flight muscle was also enhanced in bar-headed geese. This was due to an increased number of capillaries surrounding each muscle fiber and a redistribution of mitochondria within these fibers towards the cell membrane, closer to capillaries. There were also slight increases in aerobic capacity and alterations in the control of mitochondrial respiration, which could help sustain ATP turnover during prolonged flight in hypoxia.
This thesis has shown that high altitude adaptation in bar-headed geese has involved a suite of evolutionary changes at multiple steps in the O2 transport pathway. This work provides important insights into how respiratory systems evolve, and helps explain the incredible ability of bar-headed geese to fly at extremely high altitudes.
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Waldron, Francesca Mary. « Respiratory and acid-base physiology of the New Zealand rock lobster, Jasus edwardsii (Hutton) ». Thesis, University of Canterbury. Zoology, 1991. http://hdl.handle.net/10092/5959.
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McHenry, Kristen L. « Respiratory Compromise in Amyotrophic Lateral Sclerosis ». Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/2539.
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Godin, Richard Jr. « The mitochondrial respiratory profile in the locomotor muscle of Chronic Obstructive Pulmonary Disease ». Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66816.
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Rationale: Peripheral muscle alterations are suspected to contribute to disability in chronic obstructive pulmonary disease (COPD). In comparison to healthy sedentary age-matched individuals, fiber atrophy, lower proportion of type I fibers, and reduced oxidative capacity have all been reported within skeletal muscle of COPD. Although these alterations may be due to prolonged muscle disuse imposed by their ventilatory limitations, they may also be suggestive of an underlying myopathy involving a mitochondrial dysfunction. Objectives: To describe the mitochondrial respiratory profile within peripheral muscle of moderate to severe COPD patients in comparison to healthy age-matched controls. In doing so, this study aims to determine whether the abnormal locomotor muscle condition in COPD could be related to a mitochondrial dysfunction or more predominantly to the muscle inactivity associated with their sedentary lifestyle. Methods: Mitochondrial volume and respiratory profile were assessed in permeabilized vastus lateralis muscle fiber bundles of seven moderate-to-severe, non-hypoxemic and non-cachectic COPD patients and eight healthy, age-matched sedentary controls. Results: Respiration rates per milligram of fiber weight were significantly lower in COPD compared with control muscle under various respiratory states. However, when mitochondrial volume was taken into account by normalizing respiration per unit of citrate synthase activity, differences between the two groups were abolished. Respiratory ratios were also not different between the two groups. Conclusions: This study describes the respiratory profile of mitochondria from the locomotor muscle of COPD. These results are not indicative of specific mitochondrial respiratory dysfunction in the skeletal muscle of COPD patients. Rather differences at the whole muscle level merely reflect the lower mitochondrial density. This could be associated witPréambule: La détérioration du muscle périphérique est suspectée d'être un facteur contribuant à une détérioration de la qualité de vie chez les patients atteint de maladies pulmonaires obstructives chroniques (MPOC). Des modifications comme l'atrophie des fibres musculaires, une proportion diminuée de fibre de type I ainsi qu'une capacité oxydative ont été rapportées chez les patients MPOC lorsque comparé à des pairs sédentaires du même âge. Quoique ces modifications puissent être dû à une inactivité chronique qui leur est imposée par leurs limitations ventilatoires, ils peuvent aussi suggérer qu'il existe une myopathie impliquant une dysfonction mitochondriale.Objectifs: Décrire le profil respiratoire mitochondrial dans le muscle périphérique de patients MPOC modéré à sévère. Cette étude a aussi pour but de déterminer si le phénotype oxydatif du muscle squelettique chez les MPOC est associé à une défaillance mitochondriale ou à l'inactivité musculaire associé à leur mode de vie sédentaire.Méthodes: Le volume mitochondrial ainsi que le profil respiratoire a été évalués dans des fibres perméabilisées provenant du vastus lateralis de sept patients MPOC modéré a sévère ne démontrant pas d'hypoxémie ou de cachexie ainsi que chez huit sujets contrôles sédentaires, sain et du même âge.Résultats: La respiration par masse de tissus était significativement plus basse chez les patients MPOC que celle du muscle contrôle et ce, lors de différents états respiratoires. Cependant, lorsque le volume mitochondrial fut pris en considération, en normalisant par l'activité de citrate synthase, ces différences furent abolies. Les ratios respiratoires ne différaient pas entre les deux groupes expérimentaux. Conclusions: Ces résultats n'indiquent pas qu'il existe de dysfonction mitochondriale dans le muscle locomoteur du patient MPOC. Les écarts de cap
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Jackson, Elizabeth Anne. « A critical evaluation of respiratory function testing in spontaneously breathing and ventilated infants ». Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299878.
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Herlenius, Eric. « Respiratory activity in medulla oblongata and its modulation by adenosine and opioids / ». Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3240-9/.
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O'Brien, Louise Margaret. « Oxygen saturation and its relationship with breathing patterns in healthy full term infants throughout their first 24 hours of life ». Thesis, Keele University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265039.
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Pandit, Jaideep Jagdeesh. « The effects of exercise on the chemical control of breathing in man ». Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:09156247-2a9b-4c25-b51a-7b3669d6319e.
Texte intégralRésumé :
This thesis is concerned with the chemical control of breathing during exercise in humans. Chapter 1 reviews some of the relevant studies in animals and humans. Chapter 2 describes the experimental apparatus and the technique of dynamic end-tidal forcing performed using a computer-controlled gas-mixing system. Chapter 3 describes a study of the effects of sustained hypoxia on ventilation during steady exercise. The acute ventilatory response to hypoxia (AHR) was increased during exercise as compared with rest, but the magnitude of the subsequent decline in ventilation (HVD), expressed as a fraction of the AHR, was reduced. A simple model of the hypoxic peripheral chemoreflex is proposed, in which the mechanisms underlying AHR and HVD are functionally separate and can be independently modulated by external factors. Chapter 4 assesses changes in peripheral chemoreflex sensitivity to hypoxia in terms of the degree of decline in AHR measured in the resting periods shortly after prior conditioning periods of hypoxia and/or exercise. At rest, a second AHR measured 6 min after a period of sustained hypoxia had declined by 30% as compared with the initial AHR. In contrast, the AHR measured in the resting period after a period of sustained hypoxic exercise was only 11% smaller in magnitude than the AHR measured after a period of euoxic exercise. The results suggest that the degree to which hypoxic sensitivity declines during sustained hypoxia is genuinely attenuated, rather than masked, by exercise. Chapter 5 describes the changes in respiration during prolonged exercise breathing air with and without added CO2. During prolonged poikilocapnic exercise, ventilation remained constant, but metabolic CO2 production, respiratory quotient and end-tidal PCO2 declined; a result which suggests that in man, ventilation can be dissociated from the CO2 flux. During hypercapnic exercise, ventilation progressively increased; this was interpreted as being due to a correction by end-tidal forcing of the natural tendency for end-tidal CO2 to decline, together with an independent effect of CO2 per se on the ventilation. Chapter 6. Electrical muscle stimulation was used as means of inducing non-volitional exercise. Electrically-induced exercise increased the AHR as compared with rest, and with voluntary exercise at matched external work rate. The AHRs during electrical stimulation and voluntary exercise matched to the internal work rate were similar. Chapter 7. Electrical muscle stimulation was used in paraplegic subjects in whom there would be no neural control of exercise. Electrically-induced exercise increased the AHR as compared with rest. When compared with the data from Chapter 6, the results suggest that the observed increase in AHR during normal voluntary exercise can be wholly accounted for by the increase in metabolic CO2 production, or closely related factors. Chapter 8 presents a brief summary of the findings in this thesis.
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Schaeffer, Michele. « Physiological mechanisms of sex differences in exertional dyspnea : role of neural respiratory motor drive ». Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119732.
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Dyspnea, the awareness of an increase in breathing discomfort, is commonly experienced during physical activity in healthy individuals and in patients with cardiopulmonary disease. It is well established that the intensity of perceived dyspnea is consistently higher during exercise in healthy women compared to men, regardless of age, height, and weight. However, the mechanism(s) of this sex-related difference in activity-related dyspnea is/are poorly understood and represented the primary focus of this thesis.Compared to men, women have smaller lungs, narrower airways, and weaker breathing muscles. These anatomical differences manifest as greater mechanical constraints on ventilation, particularly during the stress of exercise when ventilatory requirements are high. In addition, the amount of work the breathing muscles must perform in order to move a given volume of air into and out of the lungs during exercise is considerably higher in women than men. It is reasonable to predict that, because of these differences, the central nervous system must activate the respiratory muscles (particularly the diaphragm) to a greater extent during exercise in women compared to men to achieve the same level of ventilation and that this higher respiratory muscle activation may account for the increased perception of activity-related dyspnea in women. While it is not feasible to directly measure the neural output of the brains' respiratory control center at rest or during exercise in humans, central neural respiratory motor drive can be assessed indirectly by quantifying the electromyogram of the crural diaphragm (EMGdi) using a special electrode catheter positioned in an individual's esophagus. To date, no previous study, in health or disease, has examined whether the combination of relatively greater dynamic mechanical ventilatory constraints and a higher EMGdi (i.e., neuromechanical uncoupling of the respiratory system) during exercise in women is responsible, at least in part, for sex differences in activity-related dyspnea. To address this important question we compared detailed assessments of EMGdi, respiratory muscle function, ventilation, breathing pattern, operating lung volumes, cardio-metabolic function, and dyspnea intensity and unpleasantness ratings during symptom-limited incremental bicycle exercise testing in 25 healthy, young (20-40 yrs) women and 25 age-matched men. Our results demonstrated relatively greater mechanical constraints on tidal volume expansion at any given ventilation during exercise in women compared to men. The present study was the first to demonstrate that esophageal electrode catheter-derived measures of EMGdi were consistently higher at any given ventilation during exercise in women compared with men and that these differences reflected, in large part, the presence of relatively greater dynamic mechanical ventilatory constraints in women. In keeping with the results of previous studies, sensory intensity and unpleasantness ratings of dyspnea were higher at any given ventilation during submaximal exercise in women compared to men. However, in contrast to our a priori hypothesis, these perceptual differences could not be readily explained by greater neuromechanical uncoupling of the respiratory system, but primarily reflected the awareness of a relatively higher EMGdi (or central neural respiratory motor drive) needed to achieve any given ventilation during exercise in the setting of greater dynamic mechanical ventilatory constraints in women. These findings may have implications for our understanding of the physiological mechanisms of sex differences in activity-related dyspnea in variants of health (e.g., aging) and in patients with cardiopulmonary disease.La dyspnée, définie comme la conscience d'une augmentation de gêne respiratoire, est souvent connu pendant l'activité physique chez les sujets sains ainsi que chez les patients ayant une maladie cardio-pulmonaire. Il est bien établi que l'intensité de la dyspnée perçue est systématiquement plus élevée au cours de l'exercice chez les femmes en bonne santé par rapport aux hommes, indépendamment de l'âge, de la taille et du poids. Cependant le/les mécanisme(s) de cette différence sont mal compris et la clarification de ceux-ci comportent l'objet principal de la thèse en question.Comparativement aux hommes, les femmes ont de plus petits poumons, des voies respiratoires plus étroites et des muscles respiratoires plus faibles. Ces différences anatomiques se manifestent par de plus grandes contraintes mécaniques sur la ventilation, en particulier pendant le stress de l'exercice lorsque les besoins ventilatoires sont élevés. Par conséquent, le travail que les muscles respiratoires doivent effectuer afin de déplacer un volume défini d'air dans les poumons pendant l'exercice est considérablement plus élevé chez les femmes que chez les hommes. En raison de ces différences, nous prévoyons que le système nerveux central doit activer les muscles respiratoires (notamment le diaphragme) dans une plus grande mesure chez les femmes pour atteindre le même niveau de ventilation et que cette activation supérieure peut expliquer la perception accrue de la dyspnée liée à l'activité chez les femmes. Même s'il n'est pas possible de mesurer directement les signaux envoyés par le centre de contrôle respiratoire chez l'homme, le contrôle moteur de la respiration peut être évalué indirectement en quantifiant l'électromyogramme du diaphragme crural (EMGdi) en utilisant un cathéter à électrode spécialisée placée dans l'oesophage d'un individu. À ce jour, aucune étude n'a examiné si la combinaison de contraintes ventilatoires mécaniques plus grandes et d'un EMGdi plus élevé pendant l'exercice chez les femmes est responsable des différences de sexe dans la dyspnée liée à l'activité. Nous avons donc comparé des évaluations détaillées de EMGdi, de fonction musculaire respiratoire, de ventilation, de modèle de respiration, de volumes pulmonaires opérationnels, de fonction cardio-métabolique, et d'intensité de la dyspnée et des cotes de désagréments lors de tests d'exercice incrémental de vélo dans 25 jeunes (20-40 yrs) femmes saines et 25 hommes sains du même âge. Nos résultats démontrent des contraintes mécaniques sur l'expansion du volume courant pendant l'exercice plus fortes chez les femmes par rapport aux hommes. La présente étude est la première à démontrer que les mesures de cathéter à électrodes œsophagiennes dérivés de EMGdi étaient systématiquement plus élevés peu importe le niveau de ventilation au cours de l'exercice chez les femmes par rapport aux hommes et que ces différences reflètent, en grande partie, la présence de contraintes ventilatoires mécaniques dynamiques relativement plus grande chez les femmes. En accord avec les résultats d'études antérieures, l'intensité sensorielle et le désagrément de dyspnée ont été supérieurs à n'importe quelle ventilation donnée au cours de l'exercice sous-maximal chez les femmes par rapport aux hommes. Cependant, contrairement à notre hypothèse a priori, ces différences de perception ne peuvent être facilement expliquées par un plus grand découplage neuromécanique du système respiratoire et reflètent la conscience d'une EMGdi relativement élevée (ou moteur d'entraînement respiratoire neural central) nécessaire pour atteindre une ventilation donnée pendant l'exercice dans le cadre de contraintes ventilatoires mécaniques dynamiques plus grande chez les femmes. Ces résultats pourraient avoir des implications dans notre compréhension des mécanismes de différences de sexe dans la dyspnée liée à l'activité dans les variantes de la santé et chez les patients ayant une maladie cardio-pulmonaire.
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Tiller, Nicholas B. « Respiratory mechanics during upper body exercise in healthy humans ». Thesis, Brunel University, 2014. http://bura.brunel.ac.uk/handle/2438/11551.
Texte intégralRésumé :
The physiological responses to upper-body exercise (UBE) are well established. Few published studies, however, have attempted to elucidate the mechanical ventilatory responses to UBE. There is empirical evidence that respiratory function may be compromised by UBE during which the ventilatory and postural functions of the ‘respiratory’ muscles may be exacerbated. Therefore, the aims of this thesis were: 1) to characterise the mechanical-ventilatory responses to UBE in healthy subjects; 2) to explore the putative mechanisms that underpin the respiratory responses to UBE; and 3) to assess whether the mechanical-ventilatory stress imposed by UBE induces contractile fatigue of the respiratory muscles. Compared to lower-body exercise (LBE; leg cycling) at ventilation-matched work rates, UBE (arm-cranking) resulted in constraint of tidal volume, higher respiratory frequency, and greater neural drive to the respiratory muscles. Furthermore, end-expiratory lung volume was significantly elevated during peak UBE compared to LBE (39 ± 8 vs. 29 ± 8% vital capacity, p < 0.05) and was independent of expiratory flow limitation. In assessing the influence of cadence on cardiorespiratory function and respiratory mechanics, submaximal arm-cranking at high cadence (90 rev.min-1) induced significantly greater cardiorespiratory stress, a trend towards elevated intra-thoracic pressures and significantly greater perceptions of dyspnoea than at low cadence (50 rev.min-1). Furthermore, there was a greater prevalence of locomotor-respiratory coupling at high cadences (p < 0.05), suggestive of greater antagonistic loading of the thoracic muscles, likely the result of static postural contractions. Finally, there was objective evidence of abdominal muscle contractile fatigue in response to severe- but not heavy-intensity UBE. Specifically, there was a 22% decrease in gastric twitch pressure from pre- to post-exercise in response to magnetic stimulation of the thoracic nerves (p < 0.05). However, there was limited evidence of exercise-induced diaphragm fatigue, as assessed using magnetic stimulation of the phrenic nerves (p > 0.05). In conclusion, mechanical-ventilatory function may be compromised during UBE due to complex interactions between thoracic muscle recruitment, central neural drive and thoracic volume displacement. This thesis presents novel findings which may have important functional implications for clinical populations who report breathlessness during activities of daily living that involve the upper-body, as well as for athletes engaged in upper-body sports.
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Ferreira, Matos Gomes Rute. « Respiratory mechanics in small animals : influence of size and age ». Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38188.
Texte intégralRésumé :
Although rodents have been widely used in respiratory research, there are still only limited data comparing respiratory mechanics between different species of small animal. In order to provide further insight into the mechanical behavior of the respiratory systems of different sized small animals, accurate measurements of respiratory impedance (Zrs) were made in four different rodent species and in the developing rat over a broad range of frequencies at various levels of positive end-expiratory pressure (PEEP). PEEP dependencies of airway and tissue properties were interpreted in terms of physiological phenomena such as airway closure and airway-parenchymal interdependence forces. In adult animals, Zrs was fitted to a model including a Newtonian resistance (R) in series with a constant-phase tissue compartment. In general, rodent respiratory parameters obeyed the same scaling laws described in other species, but rabbits had a relatively higher elastance than one would predict from previously published allometric relationships. This is probably due to the rabbit's proportionately smaller airspace volume. R normalized to body weight was lower in smaller species suggesting that they have proportionately wider airways compared to larger animals. By using computer models of the asymmetric airway tree to estimate airway resistance (Raw), we confirmed that the larger of two isomorphic rodent species has relatively higher Raw. Moreover, we showed that both the airway dimensional scaling differences and the asymmetric arrangement of the individual airways are responsible for the relative differences in Raw between smaller and larger animals. Finally, in the developing rat, elastance and resistance normalized to lung weight decreased progressively with age, suggesting that intrinsic changes in the mechanical properties of the respiratory system occur with development. Parenchymal interdependence forces manifested themselves in animals as young as 10 days of age, with PEEP
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Saywell, Shane Anthony. « The thoracic spinal interneurone : physiology, morphology and pharmacology relating to the transmission of respiratory drive ». Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342278.
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Sullivan, Kevin J. « Factors affecting the compliance of the lungs and respiratory system in newborn mammals ». Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75372.
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The effect of lung deformation upon its mechanical properties was studied by measuring the quasi-static (Cstat) and dynamic (Cdyn) compliances of excised newborn piglet lungs deformed by a vertical pleural surface pressure gradient. Cstat was not affected by deformation. Cdyn was less than Cstat in the deformed and undeformed lungs but the difference was greater in the deformed lungs. This behavior suggests that distortion of the chest wall may increase the external (PV) work of breathing in newborns.The contribution of lung viscoelasticity to the difference between Cstat and Cdyn of the undeformed lung was examined by measuring stress relaxation, Cstat, and Cdyn of excised lungs from newborn kittens and adult cats. The relative difference between Cdyn and Cstat and the magnitude of stress relaxation decreased with age, indicating that the viscous nature of the newborn's lungs causes larger, rate dependent changes in its compliance compared to the adult's.
Age related changes in the viscoelastic properties of the rat respiratory system were examined in rats between 1 and 40 days old. The rate of stress relaxation increased in the first week and thereafter decreased. Mean rates of stress relaxation were used to predict rate dependent changes in the passive recoil pressure of the respiratory system using an empirical model of viscoelasticity. Predictions were close to actual values suggesting that frequency dependent changes in the dynamic compliance of the newborn's respiratory system can occur independently of mechanisms involving the distribution of ventilation.
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McHenry, Kristen L. « Respiratory Compromise in the ALS Patient ». Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/2536.
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Dechman, Gail Sterns. « The effect of lung volume below normal functional residual capacity on respiratory system mechanics ». Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41568.
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This thesis examines changes in the mechanical behaviour of the canine and human respiratory systems to changes in lung volume below normal functional residual capacity (FRC). In open chested dogs lung elastance (E$ sb{ rm L}$) increased and lung resistance (R$ sb{ rm L}$) changed little with decreases in positive end-expiratory pressure (PEEP) of the ventilatory circuit. The dominance of plastoelastic lung tissue properties at low lung volumes was used to interpret the lack of change in R$ sb{ rm L}$. Computed tomography demonstrated that pleural effusion (PE) created atelectasis in dependent caudal lung regions which contributed to the overall lung volume loss. PE produced a decrease in only lung vertical height while chest wall dimensions changed both vertically and horizontally. E$ sb{ rm L}$ and R$ sb{ rm L}$ increased while elastance and resistance of the chest wall were little affected by these shape and density changes. In close-chested, anesthetised, paralysed, ventilated humans a decrease in PEEP below normal FRC caused an increase in R$ sb{ rm L}$, E$ sb{ rm L}$ and both chest wall elastance and resistance. Median sternotomy caused E$ sb{ rm L}$ to increase with increasing PEEP while the negative volume dependence of R$ sb{ rm L}$ remained. Most of the difference between open-chested and closed-chested E$ sb{ rm L}$ was presumably due to lung collapse in the open-chested state.
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Chen, Li-Yen. « The Respiratory Physiology and Energy Metabolism of Freshwater Mussels and Their Responses to Lack of Oxygen ». Diss., Virginia Tech, 1998. http://hdl.handle.net/10919/30670.
Texte intégralRésumé :
Understanding the respiratory physiology and energy metabolism is important for establishing the dissolved oxygen (DO) requirements of freshwater mussels, determining the metabolite(s) indicative of environmental stress, and interpreting environmental conditions based on physiological indicators of mussels. Three studies were undertaken to address these questions. The first study was conducted with seven mussel species collected from reservoir and riverine habitats. The two objectives were to determine the diurnal patterns of valve gaping of freshwater mussels from different habitats, and to monitor heart rate changes of a mussel species that exhibited the diurnal gaping. The results showed that night gaping is evident for the mussels collected from lentic areas, but not for those collected from lotic areas. The heart rate of Pyganodon grandis increased when they gaped. The second study was conducted with nine species of freshwater mussels from different habitats. The three objectives were to determine the patterns (i.e., regulator and conformer) of oxygen consumption (OC) rate under declining DO, evaluate the effects of temperature on ability to regulate OC under declining DO, and finally to use this information to predict DO criteria for maintaining freshwater mussels in captivity. The results showed that mussels living in the habitats subjected to low DO have a better ability to regulate the OC and were more tolerant to hypoxia. The third study assessed three mussel species from different habitats with different abilities to regulate OC under low DO. The two objectives in this study were to identify the energetic metabolite changes under different DO levels and air exposure for the three species, and to determine the appropriate tissue(s) and metabolite(s) to use for estimating the stress in mussels. The results showed that different biochemical strategies were used by Villosa iris, Elliptio complanata, and Pyganodon grandis. Villosa iris had the lowest anaerobic capacity. Elliptio complanata had a more efficient anaerobic metabolism, and P. grandis reduced energy metabolism under low DO and air exposure. posterior adductor muscle, gill and mantle were good tissues for evaluating hypoxic stress. The mantle tissue had the highest glycogen store and was the best tissue for non-lethal study of physiological condition.Ph. D.
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Fuller, David Dwight 1970. « Respiratory-related control and functional significance of tongue protrudor and retractor muscles ». Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282801.
Texte intégralRésumé :
The mammalian upper airway includes the larynx, pharynx, and nose. Respiratory-related contraction of the skeletal muscles situated in and around these regions influences upper airway diameter and compliance. The pharynx is the most collapsible upper airway segment, and its diameter and compliance depend in part on tongue position and stiffness. These parameters are controlled by the genioglossus (GG) muscle, which protrudes the tongue, and the hyoglossus (HG) and styloglossus (SG) muscles, which retract the tongue. Prior work has focused almost exclusively on the GG, leaving a gap in the literature regarding the respiratory control and function of the tongue retractors. Accordingly, our overall purpose was to test the hypothesis that the tongue protrudor and retractor muscles are co-activated during inspiration and that co-activation promotes airway patency. Experiments were conducted using supine, anesthetized, tracheotomized rats. Tongue movements were quantified as either protrusive or retractive by connecting the tip of the tongue to a force transducer. The protrudor and retractor muscles were co-activated during quiet breathing and their activities increased in parallel when breathing was stimulated with high CO2 or low O 2. Co-activation of protrudor and retractor muscles was always accompanied by tongue retraction. Neural drive to both GG and HG muscles was increased in parallel when lung volume feedback was removed by single breath tracheal occlusion. The functional significance of tongue muscle co-activation was examined using an isolated upper airway preparation. Co-activation increased airflow rates and stiffened the airway, whereas selective protrudor muscle activation increased airflow but did not alter airway stiffness. A standard fatigue protocol was used to examine the influence of hypoxia on the endurance performance of tongue protrudor and retractor muscles; the results indicate that hypoxia attenuates tongue muscle endurance, possibly via impaired neuromuscular transmission. It is concluded that, in the rat, (1) the tongue protrudor and retractor muscles are co-activated during inspiration, and respond in parallel to increases in respiratory drive; (2) tongue muscle co-activation results in tongue retraction and stiffening of the pharyngeal airway, and (3) the endurance of the tongue muscles is impaired during hypoxia.
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De, Cort Susan Caroline. « Measurement of hypoxic ventilatory drive at rest and during exercise in normal man ». Thesis, University of Edinburgh, 1989. http://hdl.handle.net/1842/18823.
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Brockett, Emma Grace. « An investigation of respiratory abnormalities in a male and female mouse model of Rett Syndrome ». Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4097/.
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Rett Syndrome (RTT) is a severe neurodevelopmental disorder affecting 1 in 10,000 girls and is often associated with respiratory abnormalities. RTT is almost exclusively caused by loss-of-function mutations in the human MECP2 gene. It remains unknown as to whether the respiratory abnormalities seen in RTT patients and MeCP2 deficient animals may be due to problems with respiratory rhythmogenesis or the result of an inappropriate chemosensitive response. The main aim of this thesis was to investigate the respiratory abnormalities presented in a male and female mouse model of RTT syndrome. In a male mouse model, the endogenous Mecp2 gene was silenced by insertion of a Lox-Stop cassette, which mimicked a number of RTT symptoms, including disordered breathing (Guy et al., 2007). The Mecp2 gene was reactivated by Tamoxifen(TM)-induced deletion of the Lox-Stop cassette. As such, the progression and development of respiratory disturbances were monitored in the early stages of MeCP2 deficiency and also assessed during and after gene reactivation. Respiratory parameters were recorded using whole body plethysmography, a non-invasive method of recording respiratory behaviour. Compared to WT, MeCP2 deficient male mice had an increased respiratory frequency and increased number of sighs prior to gene reactivation. The fact that animals were still viable suggests that neuronal development can occur in the absence of MeCP2, but signs of respiratory instability e.g. the increased number of sighs, indicate that MeCP2 may be required for neuronal maturation as the animal develops. Gene reactivation reduced respiratory frequency and the number of sighs in MeCP2 deficient mice to a level comparable with WT suggesting that TM-induced activation of Mecp2 can reverse some of the respiratory abnormalities. Since RTT syndrome is a predominantly female based disorder it was of benefit to observe the progression of the respiratory phenotype in a female model. Female mice which were heterozygous for the Mecp2-null mutation were also studied using plethysmography. It was observed that at 23 wks of age, following a period of normal development, the Mecp2+/- mice began to display an increased number of respiratory abnormalities compared to WT animals which suggested an inability of the respiratory network to maintain optimal function. Also, the respiratory response to hypoxia was significantly greater in Mecp2+/- mice compared to WT, yet the hypercapnic response of the two genotypes was comparable. This indicates that the response to hypoxia and hypercapnia are mediated by two different mechanisms and that the hypoxic response may be affected by a reduction in the level of MeCP2. Neuromodulators such as noradrenaline and serotonin are important in modulation of the respiratory pattern and the chemosensitive response. Previous research has implicated changes in bioamine content in the pathophysiology of RTT patients and MeCP2 deficient animals (Riederer et al., 1985; Ide et al., 2005; Viemari et al., 2005; Roux et al., 2010) Thus, cells expressing tyrosine hydroxylase (TH), a marker for noradrenergic cells, and cells expressing 5-HT were quantified in the brainstems of MeCP2 deficient male mice to observe how the absence and subsequent reactivation of Mecp2 may affect noradrenergic and serotonergic cell number. Compared to WT, MeCP2 deficient mice exhibited a trend towards a decrease in the number of TH and 5-HT expressing cells in various noradrenergic and serotonergic regions of the brainstem, which may account for the development of the respiratory abnormalities in the mutant mice. It was also found that reactivation of Mecp2 did not restore the number of MeCP2 expressing cells to WT level. MeCP2 was often found to be co-expressed with 5-HT and TH, yet many MeCP2 positive neurons were not found to be 5-HT or TH positive indicating that these MeCP2 expressing neurons may be co-localised with another as yet unidentified neuromodulator. Interestingly, reactivation of Mecp2 appeared to occur at a greater rate in noradrenergic TH expressing neurons than 5-HT expressing neurons. Whilst studying MeCP2 deficient male mice it was noted that some of the mutant animals began to develop rale-like rattling within the chest and also began to foam at the mouth. Much of the research in RTT syndrome focuses on the neurological aspect, whereas this phenotype indicated a problem within the lungs. Lungs of WT and MeCP2 deficient mice were removed and processed with various histological stains to highlight various aspects of the lung morphology. Comparison of WT and MeCP2 deficient tissue revealed that there was a trend towards an increase in the amount of elastin surrounding airways and an increase in the thickness of the interalveolar septum in MeCP2 deficient mice compared to WT. An increase in interalveolar septum may interfere with ventilation and may account for the increased occurrence of sighing observed in the male MeCP2 deficient mice. These morphological changes in the lung may indicate that the respiratory abnormalities of RTT may not be solely neurological. Since changes in the morphology of the lung were clearly present in the male with evidence of increased elastin deposits surrounding the airways, investigation into the presence of pulmonary arterial hypertension (PAH) was carried out in the female model. Results indicated that there was a trend towards a higher right ventricular pressure in Mecp2+/- animals compared to WT, along with a trend towards right ventricular hypertrophy, indices of the presence of PAH. In conclusion, Mecp2 has been shown in vivo to be involved in both the development and maintenance of neurons involved in the respiratory network, both neuromodulatory and chemosensitive, and the absence or reduction of MeCP2 is also proposed to have a novel role in the development of lung pathology in MeCP2 deficient mice.
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Osiki, Prisca Ofure. « The effect of beta-oxidation or TCA cycle inhibition on mitochondrial function and the sensitivity of high resolution respiratory detection ». Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/30944.
Texte intégralRésumé :
INTRODUCTION: A dysfunction in fatty acid beta-oxidation (β-oxidation), particularly medium chain acyl-CoA dehydrogenase (MCAD) dysfunction is a major cause of mortality and its diagnosis is usually achieved by measuring specific protein activities or metabolites in blood and/or urine samples. However, these methods do not account for secondary defects that accompany primary deficiency; such as where measures of disruption in fatty acid metabolism do not account for defects in the TCA cycle and oxidative phosphorylation. These metabolic pathways are connected and dysfunction in one pathway (primary) could lead to dysfunction in the other (secondary). We propose the use of methods that combines all aspects of the bioenergetics module (enzyme activity in substrate oxidation within each individual pathway, transfer of electrons through the electron transport system (ETS) and oxidative phosphorylation for ATP generation) may be a more effective assessment technique. High resolution respirometry (HRR) is a recently developed technique that accounts for substrate oxidation, electron transfer via the ETS and oxidative phosphorylation. It measures the rate of oxygen consumption or flux at different respiratory states when appropriate substrates, uncouplers and inhibitors (SUIT protocols) are used. With this method, two substrate combinations are commonly used to assess medium-chain fatty acid β-oxidation; a) Octanoylcarnitine and carnitine, which is partial to the β-oxidation cycle alone, and b) Octanoylcarnitine and malate, which assesses the influence of the TCA cycle. Additionally, a combination of pyruvate, glutamate and malate is used to assess oxidation within the TCA cycle. We investigated the sensitivity of commonly used substrate combinations in HRR assessment to detect changes in mitochondrial respiration and dysfunction induced by the inhibition of either β-oxidation or the TCA cycle in C2C12 myotubes. Furthermore, we assessed MCAD, citrate synthase and aconitase enzyme activities when β-oxidation or TCA cycle was inhibited in C2C12 myotubes. METHODS: C2C12 myotubes were differentiated for 6 days and treated for 12 hours with a high or a low concentration of one of two inhibitors as follows; a) 2 mM or 8 mM 2-mercaptoacetate to inhibit medium chain acyl-CoA dehydrogenase (MCAD); b) 6 mM or 9 mM fluorocitrate to inhibit aconitase. Each treatment was compared to control myotubes grown for the same length of time without the addition of inhibitors. The activities of MCAD, aconitase and citrate synthase were determined. In addition, mitochondrial respiration measured as O2 flux at Routine, Leak, OXPHOS and ETS respiratory states were assessed in an Oxygraph-2K after inhibition or in control treatments using; i) Octanoylcarnitine and carnitine ii) Octanoylcarnitine and malate iii) pyruvate, malate and glutamate substrate combinations. For each assessment we corrected O2 flux recorded at each state to; a) approximate number of cells (pmol O2/s/million cells) b) protein concentration (pmol O2/s/mg protein) c) Flux control ratio (FCR) of each state to the maximum ETS capacity; ETSFAO+CI+CII (convergent electron flow from Fatty acid oxidation (FAO), Complex I (CI) and CII) d) FCR to either FAO-linked ETS capacity; (ETSFAO) or CI-linked ETS capacity (ETSCI). RESULTS: Treatment of cells with either a low or high concentration of 2-mercaptoacetate to inhibit MCAD resulted in no significant difference in MCAD activity. Fluorocitrate treatment decreased aconitase activity with low treatment (p = 0.011) compared to control, and conversely it increased MCAD activity in high treatment compared to control (p = 0.024). Both 2-mercaptoacetate (p = 0.03) and fluorocitrate (p < 0.01) treatment at high concentrations resulted in increased citrate synthase activity, compared to low concentration and control. Mitochondrial respiration with octanoylcarnitine and carnitine substrate combination was not altered with MCAD or aconitase inhibition. Octanoylcarnitine and malate substrate combination showed a decrease in mitochondrial respiration at the following respiratory states with both MCAD and aconitase inhibition; Routine (p = 0.01), LeakFAO (p = 0.029), OXPHOSFAO (p = 0.006), ETSFAO (p = 0.008), ETSFAO+CI (p = 0.017). FCR of each state to the maximum capacity (ETSFAO+CI+CII) revealed a decrease with both MCAD and aconitase inhibition at the following states; routine (p = 0.001), OXPHOSFAO (p = 0.003), ETSFAO (p = 0.018), ETSFAO+CAR (p = 0.008) and ETSFAO+CI (p = 0.027). Pyruvate, malate and glutamate substrate combination showed decreased mitochondrial respiration with MCAD inhibition at the following respiratory states; Routine (p = 0.004), LeakCI (p = 0.007), OXPHOSCI (p = 0.003), ETSCI (p = 0.003), ETSCI+FAO (p = 0.01) and ETSCI+FAO+CII (p = 0.003). FCR of each state to the maximum capacity (ETSCI+FAO+CII) decreased with both MCAD and aconitase inhibition at Routine (p = 0.024), OXPHOSCI (p = 0.024) and ETSCI (p = 0.035) states. DISCUSSION: The main finding of this study was related to two of the SUIT protocols 1) octanoylcarnitine and malate, and 2) pyruvate, malate and glutamate. These protocols were sensitive in showing decreased respiratory capacity and coupling control ratios and may be appropriate for assessing changes in oxidative metabolism when there is a defect in β-oxidation and/ or the TCA cycle. On the other hand, octanoylcarnitine and carnitine substrate combination is not sensitive to detect dysfunction induced by inhibition of either β-oxidation or TCA cycle. Irrespective of the enzyme inhibited, HRR detected dysfunction in complex I (CI), although, when aconitase was inhibited, reduced CI-linked respiration was more pronounced compared to MCAD inhibition. Furthermore, primary inhibition of MCAD to inhibit β-oxidation may have caused secondary inhibition of TCA cycle via aconitase, shown in decreased TCA cycle CI-linked respiration where MCAD was inhibited. In contrast, primary inhibition of aconitase seemed to be compensated for by increased MCAD activity and mitochondrial respiration related to β-oxidation. Lastly, enzyme assaysshould not be used as standalone techniques for assessing metabolic dysfunction at the level of TCA, β-oxidation and the mitochondria since they are not sensitive to low level defects, nor do they account for secondary interactions that influence either TCA or betaoxidation. HRR is useful to assess mitochondrial respiration and dysfunction, when using an appropriate substrate combination and should be used in combination with the more traditional enzyme activity assays.
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Bonin, Aly Hassan Marie-Claire. « Studies on the respiratory metabolism of the marine bacterium Alteromonas haloplanktis ». Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=72490.
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McHenry, Kristen L. « Professional and Ethical Standards in Respiratory Care ». Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/2538.
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Brown, Anne Christine 1962. « Effects of salinity and temperature on the respiratory physiology of the Dungeness crab, Cancer magister, during development ». Thesis, Thesis (Ph. D.)--University of Oregon, 1991, 1991. http://hdl.handle.net/1794/9845.
Texte intégralRésumé :
Typescript.
Includes vita and abstract.
Bibliography: Includes bibliographical references (leaves 172-183).Cancer magister, the Dungeness crab, occurs in different habitats during its life cycle, habitats which vary widely in the magnitude of salinity and temperature changes. Cancer magister hemocyanin also changes in structure and oxygenation properties during development. The following question was considered in this thesis: what are the effects of environmental salinity and temperature on metabolic rates, ionic and osmotic regulation and hemocyanin oxygen affinity in Q. magister during development. Metabolic rates and hemolYmph ionic and osmotic concentrations were measured in the megalopa, 1st juvenile, 5th juvenile and adult crab eight hours after acute exposure to 100% seawater (=32 ppt), 75% seawater and 50% seawater at both 10°C and 20°C. The oxygen binding properties of the whole hemolymph from these stages in 100% seawater at 10°C was determined. The effects of calcium and magnesium on the oxygen affinity of purified hemocyanin from different stages were also determined. In 100% seawater, routine metabolic rates of the four stages scale with body mass over the size range, 0.05 gm to 500 gm. The Q10 (10°C to 20°C) for the megalopa is higher in 75% seawater and 50% seawater than in 100% seawater. For the 1st juvenile, 5th juvenile and adult the Q10 values (10°C to 20°C) are independent of salinity. The megalopa, 1st juvenile and 5th juvenile are weaker regulators of hemolymph chloride, sodium and osmotic concentrations than the adult. The megalopa and adult, unlike the 1st juvenile and 5th juvenile, strongly regulate hemolymph calcium in reduced salinity. In 100% seawater hemolymph magnesium is significantly higher in the megalopa, 1st juvenile and 5th juvenile than in the adult. The oxygen affinities of whole hemolymph from the four stages are indistinguishable when adjusted for endogenous L-lactate concentrations; the Bohr coefficients are not significantly different among stages. The effect of magnesium on oxygen affinity of purified adult hemocyanin is influenced by proton concentration; the effect of calcium is independent of proton concentration. In 100% seawater, endogenous inorganic ion concentrations in the whole hemolymph of the various stages reduce the intrinsic stage specific differences in hemocyanin oxygen affinity.
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Santin, Joseph M. « CO2/pH Signaling of Respiratory Control Neurons in the Bullfrog, Lithobates catesbeianus : Development of a Comparative Model ». Wright State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1369304052.
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Grönkvist, Mikael. « Ventilation distribution in the lung periphery measured by inert gas washout : influence of increased gravity, anti-G suit pressure, body posture, and breathing pattern / ». Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/tek896s.pdf.
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McHenry, Kristen L. « Safe Practice ». Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/2535.
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