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1
Dreier, Jens P. "Cortical spreading ischaemia and delayed ischaemic neurological deficits after subarachnoid haemorrhage." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=970109342.
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2
Willems, Laura E., and n/a. "Adenosine and Ischaemia in Young To Aged Hearts." Griffith University. School of Medical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20061011.163451.
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Ischaemic heart disease is a major contributor to premature death and heart failure in the Westernised world. Ischaemic injury within the heart may be beneficially modulated by the nucleoside adenosine. Derived from catabolism of ATP, adenosine was initially known as a potent bradycardic and hypotensive agent. However, more recently the protective function of adenosine has been investigated. The protective effects of adenosine are mediated via activation of adenosine receptors: A1, A2A, A2B, and A3 receptors. Activation of these potentially protective (or retaliatory) adenosine receptors hinges upon accumulation of adenosine during ischaemia-reperfusion. This Thesis examines the role and mechanisms of adenosine mediated cardioprotection in young and aged hearts, exploring endogenous and exogenous adenosine receptor activation, genetic manipulation of A1 receptors and adenosine deaminase and pharmacological manipulation of adenosine metabolism. The effects of age on ischaemic responses and adenosine handling and protection are also assessed. The core approach to assess each of the above issues involved the Langendorff isolated mouse heart preparation. Experiments within Chapter 3 focuses on the contractile effects of adenosine receptors in normoxic hearts. This study indicates A2A receptors have no direct effect on contractility, while adenosine exerts positive inotropy independently of coronary flow and perfusion pressure (i.e. Independent of the Gregg phenomenon). In addition, investigations in genetically modified hearts hint at positive inotropy in response to A1 receptors. Since the latter is only evidenced in modified lines, it is possible A1-mediated inotropy may be abnormal or supraphysiological. In Chapter 4 the impact of genetic 'deletion' of A1ARs and/or adenosine deaminase (ADA) on intrinsic tolerance to ischaemia were studied. Data demonstrate that genetic deletion of A1 receptors significantly limits the ability of the mouse myocardium to withstand injury during ischaemic insult. Thus, providing strong support for a role of A1ARs in determining intrinsic tolerance to ischaemia-reperfusion. ADA KO mice confirm protection afforded by endogenous adenosine and the notion of adenosine metabolism modification as a protective strategy. Interestingly, effects of A1AR KO differ from A1AR overexpression or A1AR agonism in that the latter decrease contractile diastolic dysfunction while A1AR KO selectively increase systolic dysfunction and increase oncosis without altering diastolic injury. This challenges current dogma regarding the action of A1 adenosine receptors on ischaemic injury. In Chapter 5 the effects of adenosine metabolism inhibition (via adenosine deaminase (ADA) and adenosine kinase (AK) inhibitors) were studied. Inhibition of adenosine deaminase with the drug EHNA, and adenosine phosphorylation with iodotubercidin significantly protected mouse hearts from ischaemia-reperfusion, reducing contractile dysfunction and cardiac enzyme efflux. However, inhibitors failed to improve the outcome of the aged myocardium. 8-SPT and 5-HD reduced the protective effects of EHNA and iodotubercidin demonstrating thus; cardioprotection via ADA and AK appears to rely on adenosine receptor activation and involves a mitoK ATP dependent mechanism. Since aging is of considerable importance with regard to outcomes of ischaemic heart disease, experiments in Chapter 6 focused on effects of aging (and gender) on cardiovascular function and injury during ischaemia-reperfusion. In assessing post ischaemic outcomes in hearts from young adult (2-4 months), mature adult (8 months), middle aged (12 months), aged (18 months) and senescent (24-28 months) C57/BL/6J mice, data reveal a substantial age-related decline in ischaemic tolerance (which appears selective for myocardial vs. vascular injury). The decline in ischaemic tolerance is expressed primarily within the initial 12 months in both males and females with relatively little further decline with continued aging. There is evidence of a modest improvement in tolerance in senescence vs. aged hearts possibly reflecting selection of a protected phenotype in senescent populations. In addition, mature and middle-aged female hearts showed improved tolerance to ischaemia-reperfusion compared to males, supporting a role for hormonal changes. Effects of aging and purine metabolism were studied in Chapter 7. Data suggest impaired tolerance to ischaemia-reperfusion in older hearts may stem in part from shifts in myocardial purine catabolism. Data reveal reduced accumulation of salvageable and cardioprotective adenosine and enhanced accumulation of poorly salvaged (and potentially injurious) hypoxanthine and xanthine. These changes may potentially predispose the aged myocardium to ischaemic injury and radical generation via the xanthine oxidase reaction. The final data Chapter of this Thesis describes preliminary data regarding aging, signalling and adenosine mediated protection. It was found that protein kinase C (PKC) and A1 receptors mediate protection in young hearts and also that A1 receptors appear to mediate protection via a PKC LindependentLi signalling cascade. In addition, experiments in aged hearts (attempting to elucidate mechanisms behind impaired adenosinergic protection with age) suggest a PKC-independent A1-mediated protection path may be preserved with aging, since A1 receptors continue to offer some protection while PKC activation does not. It is possible the failure of exogenous adenosine to offer protection in aged hearts may result from a lesion at or downstream of PKC.
3
Willems, Laura E. "Adenosine and Ischaemia in Young To Aged Hearts." Thesis, Griffith University, 2006. http://hdl.handle.net/10072/365196.
Full textAbstract:
Ischaemic heart disease is a major contributor to premature death and heart failure in the Westernised world. Ischaemic injury within the heart may be beneficially modulated by the nucleoside adenosine. Derived from catabolism of ATP, adenosine was initially known as a potent bradycardic and hypotensive agent. However, more recently the protective function of adenosine has been investigated. The protective effects of adenosine are mediated via activation of adenosine receptors: A1, A2A, A2B, and A3 receptors. Activation of these potentially protective (or retaliatory) adenosine receptors hinges upon accumulation of adenosine during ischaemia-reperfusion. This Thesis examines the role and mechanisms of adenosine mediated cardioprotection in young and aged hearts, exploring endogenous and exogenous adenosine receptor activation, genetic manipulation of A1 receptors and adenosine deaminase and pharmacological manipulation of adenosine metabolism. The effects of age on ischaemic responses and adenosine handling and protection are also assessed. The core approach to assess each of the above issues involved the Langendorff isolated mouse heart preparation. Experiments within Chapter 3 focuses on the contractile effects of adenosine receptors in normoxic hearts. This study indicates A2A receptors have no direct effect on contractility, while adenosine exerts positive inotropy independently of coronary flow and perfusion pressure (i.e. Independent of the Gregg phenomenon). In addition, investigations in genetically modified hearts hint at positive inotropy in response to A1 receptors. Since the latter is only evidenced in modified lines, it is possible A1-mediated inotropy may be abnormal or supraphysiological. In Chapter 4 the impact of genetic 'deletion' of A1ARs and/or adenosine deaminase (ADA) on intrinsic tolerance to ischaemia were studied. Data demonstrate that genetic deletion of A1 receptors significantly limits the ability of the mouse myocardium to withstand injury during ischaemic insult. Thus, providing strong support for a role of A1ARs in determining intrinsic tolerance to ischaemia-reperfusion. ADA KO mice confirm protection afforded by endogenous adenosine and the notion of adenosine metabolism modification as a protective strategy. Interestingly, effects of A1AR KO differ from A1AR overexpression or A1AR agonism in that the latter decrease contractile diastolic dysfunction while A1AR KO selectively increase systolic dysfunction and increase oncosis without altering diastolic injury. This challenges current dogma regarding the action of A1 adenosine receptors on ischaemic injury. In Chapter 5 the effects of adenosine metabolism inhibition (via adenosine deaminase (ADA) and adenosine kinase (AK) inhibitors) were studied. Inhibition of adenosine deaminase with the drug EHNA, and adenosine phosphorylation with iodotubercidin significantly protected mouse hearts from ischaemia-reperfusion, reducing contractile dysfunction and cardiac enzyme efflux. However, inhibitors failed to improve the outcome of the aged myocardium. 8-SPT and 5-HD reduced the protective effects of EHNA and iodotubercidin demonstrating thus; cardioprotection via ADA and AK appears to rely on adenosine receptor activation and involves a mitoK ATP dependent mechanism. Since aging is of considerable importance with regard to outcomes of ischaemic heart disease, experiments in Chapter 6 focused on effects of aging (and gender) on cardiovascular function and injury during ischaemia-reperfusion. In assessing post ischaemic outcomes in hearts from young adult (2-4 months), mature adult (8 months), middle aged (12 months), aged (18 months) and senescent (24-28 months) C57/BL/6J mice, data reveal a substantial age-related decline in ischaemic tolerance (which appears selective for myocardial vs. vascular injury). The decline in ischaemic tolerance is expressed primarily within the initial 12 months in both males and females with relatively little further decline with continued aging. There is evidence of a modest improvement in tolerance in senescence vs. aged hearts possibly reflecting selection of a protected phenotype in senescent populations. In addition, mature and middle-aged female hearts showed improved tolerance to ischaemia-reperfusion compared to males, supporting a role for hormonal changes. Effects of aging and purine metabolism were studied in Chapter 7. Data suggest impaired tolerance to ischaemia-reperfusion in older hearts may stem in part from shifts in myocardial purine catabolism. Data reveal reduced accumulation of salvageable and cardioprotective adenosine and enhanced accumulation of poorly salvaged (and potentially injurious) hypoxanthine and xanthine. These changes may potentially predispose the aged myocardium to ischaemic injury and radical generation via the xanthine oxidase reaction. The final data Chapter of this Thesis describes preliminary data regarding aging, signalling and adenosine mediated protection. It was found that protein kinase C (PKC) and A1 receptors mediate protection in young hearts and also that A1 receptors appear to mediate protection via a PKC LindependentLi signalling cascade. In addition, experiments in aged hearts (attempting to elucidate mechanisms behind impaired adenosinergic protection with age) suggest a PKC-independent A1-mediated protection path may be preserved with aging, since A1 receptors continue to offer some protection while PKC activation does not. It is possible the failure of exogenous adenosine to offer protection in aged hearts may result from a lesion at or downstream of PKC.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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4
Kelly, Stephen. "Neuroprotection and functional alterations in mice over-expressing heat shock protein 70i." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327580.
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5
Khalid, Usman. "The role of microRNAs and ischaemic preconditioning in kidney ischaemia reperfusion injury." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/95843/.
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Successful kidney transplantation transforms outcome for patients with end stage kidney disease. Delayed graft function (DGF) following Ischaemia Reperfusion Injury (IRI) is a major problem, is hard to predict or monitor, and preventative or therapeutic strategies are lacking. Ischaemic Preconditioning (IPC) may limit IRI, but results are variable and potential mechanisms are not well defined. The aims of this thesis were to study the role of microRNAs, which are post-transcriptional regulators of gene expression vital in many physiological and pathophysiological processes, in the context of IRI, IPC and DGF. An in vivo model of IRI and IPC was developed, and histological, biochemical and mRNA kidney injury marker analyses were undertaken. MicroRNAs were then profiled using both Next Generation Sequencing (NGS) and hybridisation arrays, and changes in selected microRNAs confirmed by RTqPCR. Histology scores, serum creatinine and expression of kidney injury markers were significantly reduced in IPC compared with IRI. Microarray and NGS analysis identified a highly reproducible IRI signature, which was attenuated by IPC. Subsequently, microRNAs were profiled using Taqman Low Density Array (TLDA) and validated by RT-qPCR, from urine samples of kidney transplant patients with and without DGF. A DGF microRNA profile was uncovered, with overlap to the results from the IRI model. These data have identified a microRNA signature of IRI that was attenuated by IPC, which also improved outcome. Urinary microRNAs also showed a promising capability to predict DGF in human kidney transplantation. MicroRNAs thus show significant promise as biomarkers and potential therapeutic targets in this context.
6
Banga, Neal Roop. "Effects of Ischaemia-Reperfusion Injury and Ischaemic Preconditioning on Human Liver Sinusoidal Endothelial Cells." Thesis, University of Leeds, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.515298.
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7
Mallick, Ismail Hameed. "Role of haem oxygenase in ischaemic preconditioning on the intestinal microcirculation following ischaemia reperfusion injury." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444963/.
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Intestinal ischaemia reperfusion (IR) injury is associated with various clinical conditions such as hypovolemic shock, strangulation-obstruction, cardiovascular surgery, abdominal aortic surgery and small bowel transplantation. IR injury of the intestine is a systemic phenomenon resulting in bacterial translocation, endotoxaemia, acute respiratory distress syndrome and acute hepatic injury culminating in multiple organ failure. It has been hypothesised that ischaemic preconditioning may protect against IR injury of the intestine through haem oxygenase formation. This thesis (study) investigated the relationship of haem oxygenase metabolism with intestinal microvascular perfusion, tissue oxygenation and function with ischaemic preconditioning of the intestine in an experimental model of ischaemia reperfusion injury of the small intestine. Male Sprague Dawley rats (250-300 grams) were subjected to 30 mins of ischaemia by clamping of superior mesenteric artery followed by 2 hrs (early phase) or 24 hrs (late phase) of reperfusion. Ischaemic preconditioning was performed with 10 min ischaemia and 10 min reperfusion before the sustained ischaemia. Pyrrolidine dithiocarbamate (PDTC) or Zinc Protoporrphyrrin (ZnPP) were administered to stimulate or block heme oxygenase synthesis. The study demonstrated that ischaemic preconditioning resulted in significantly improvement in intestinal microvascular perfusion, tissue oxygenation as well as decreased leukocyte-endothelial interactions and intestinal and pulmonary injury following both early and late phases of IR injury. The preconditioning effect was associated with significantly increased haem oxygenase production suggested by intestinal tissue haeme oxygenase levels as demonstrated by haem oxygenase assays and western blotting. PDTC treatment reproduced the protective effect of ischaemic preconditioning. Haem oxygenase inhibition with ZnPP antagonized the protective effect of ischaemic preconditioning. This thesis has shown that the protective effect of intestinal ischaemic preconditioning against both early and late phases of IR injury is associated with increased haem oxygenase production. These data may have important implications in intestinal surgery and transplantation and may lead to the development of pharmacological strategies for protecting the intestine from ischaemic injury.
8
Robertson, F. "The effect of remote ischaemic preconditioning on CD4 T cells following hepatic ischaemia reperfusion injury." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10047916/.
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Ischaemia Reperfusion (IR) injury is a major cause of morbidity and mortality following orthotopic liver transplantation. Remote Ischaemic Preconditioning (RIPC) reduces IR injury in small animal models. The mechanism remains unclear. The aim of this thesis was to explore the mechanism of RIPC and its clinical relevance to liver transplant recipients. Following a literature review a study was performed on optimal end points for clinical studies modulating IR injury in liver transplantation. Day 3 AST level was strongly associated with early post operative morbidity and mortality. A pilot randomised controlled trial of limb RIPC (3 cycles 5 minutes) in 40 liver transplant recipients was performed. Recruitment was successful and the intervention found to be safe and well tolerated. There was no significant difference in day 3 AST. CD4+T cell IFNγ and TNFα production was found to be significantly upregulated in patients post-reperfusion but not affected by RIPC. IFNγ and IL-2 were produced by a CD3-ve HLADR+ve cell population. Monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated following reperfusion and correlated with clinical outcomes. The T cell response to RIPC was further investigated in a murine model of RIPC and warm liver IR injury. The model demonstrated a reduction in warm liver IR injury following RIPC. Intrahepatic CD4+ T cell TNFα production was significantly increased following reperfusion and reduced by RIPC. Monocytes were recruited to the post ischaemic liver as demonstrated in the human clinical trial. MCP-1 levels and monocyte recruitment were significantly reduced following RIPC in the mouse. In conclusion clinical benefit of RIPC in OLT recipients was not achieved in this pilot study. The RIPC stimulus may be sub-optimal. CD4+T cells and monocytes were shown to have a key role in both the human and animal studies and their manipulation may provide new opportunities for modulating liver IR injury.
9
Hobbs, Catherine E., and n/a. "Perinatal hypoxia-ischaemia : neuroprotective strategies." University of Otago. Department of Anatomy & Structural Biology, 2005. http://adt.otago.ac.nz./public/adt-NZDU20070221.145910.
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Perinatal hypoxia-ischaemia is a major cause of disability, including cerebral palsy, yet a neuroprotectant which fully protects the brain remains elusive. Following a hypoxic-ischaemic insult, striatal medium-spiny neurons and hippocampal CA1 neurons are vulnerable to a complex cascade of neurotoxic events. This cascade includes energy failure, a massive release of glutamate, the formation of free radicals and caspase activation. The overall aim of this thesis was to assess the efficacy of three potential neuroprotective strategies that target this cascade from different directions. Short-term, and where appropriate, long-term, neuroprotection was investigated. The first treatment strategy aimed to suppress the generation of free radicals through treatment with the potent free radical spin trap, N-tertbutyl-(2-sulphophenyl)-nitrone (S-PBN). The second compound tested was the caspase-3 inhibitor, minocycline. Finally, the third treatment strategy combined a series of S-PBN injections with 6 hours of moderate hypothermia immediately after hypoxia-ischaemia. Hypothermia is suggested to slow the rate of the neurotoxic cascade, thus potentially allowing other neuroprotective agents greater efficacy.
Using an adaptation of the Rice et al. (1981) model, hypoxia-ischaemia was induced on postnatal day (PN) 8 in the right cerebral hemisphere. For the short-term studies, the rats were perfused at 14 days-of-age. The brains were dissected out and embedded in Technovit. Forty [mu]m serial sections were cut through the right striatum and hippocampus. The total number of medium-spiny neurons in the striatum and where appropriate, the total number of neurons in the hippocampal CA1 pyramidal layer, were stereologically determined using the optical disector/Cavalieri method.
For the long-term study, fine motor control was assessed in half of the animals through the staircase test from 9-11 weeks-of-age. Neuroprotection was assessed in the remaining animals. All animals were sacrificed at 12 weeks-of-age. The total number of striatal medium-spiny neurons was stereologically determined in the non-behavioural animals as described above.
A series of seven injections of S-PBN (100mg/kg) did not offer statistically significant neuroprotection to the striatum at one week after perinatal hypoxia-ischaemia. Similarly, a single injection of minocycline (45mg/kg) immediately after the insult did not offer significant neuroprotection to the striatum nor the CA1 region of the hippocampus at this early time-point. In contrast, when the series of S-PBN injections was combined with 6 hours of moderate hypothermia post-hypoxia-ischaemia, sterelogical analysis revealed significant neuroprotection of the striatal medium-spiny neurons to normal levels at one week after the injury. No significant neuroprotection was seen in the CA1 region of the same animals.
To assess whether this impressive striatal neuroprotection was long-lasting and whether it represented functional rescue, the final experiment in this thesis investigated rat pups at 12 weeks-of-age after exposure to hypoxia-ischaemia at PN8. Treatment with S-PBN/hypothermia offered persistent neuroprotection of striatal medium-spiny neurons and preservation of fine motor skills compared to diluent-normothermia-treated controls. The long-term behavioural outcomes were compared with normal, uninjured controls and the total number of medium-spiny neurons was compared with normal numbers from the literature. These comparisons revealed that the histological and functional integrity of the striatum was rescued to normal levels.
This is the first study to identify a treatment strategy that offers complete and long-lasting preservation of striatal neuronal numbers, by accurate and unbiased stereological methods, paired with persistent preservation of fine motor control following perinatal hypoxia-ischaemia.
10
Rowe, Jeremy Geraint. "Cerebral ischaemia complicating subarachnoid haemorrage." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320671.
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Peters, Elaine Elizabeth. "Inflammatory responses and cerebral ischaemia." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252469.
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Elliott, Perry Mark. "Myocardial ischaemia in hypertrophic cardiomyopathy." Thesis, St George's, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391632.
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Edroos, Sadat Ali. "Myocardial ischaemia-reperfusion injury and its reduction by remote ischaemic preconditioning in health and diabetes mellitus." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/31983.
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Myocardial infarction is the main cause of death in the United Kingdom. Early reperfusion of coronary artery occlusion has greatly improved mortality, though restoration of blood supply may perpetuate cell death through reperfusion injury. Preconditioning is a potent endogenous form of cardioprotection triggered through preceding brief nonperfusion of the heart’s blood supply. In remote conditioning it is triggered by intermittent tourniquet ischaemia of a limb. However a limited understanding of the mechanisms underlying transfer of a signal from the peripheries, its reception in the heart, and the impact of comorbid disease on this process hinders its application to the clinical setting of myocardial infarction. This work trials several models of reperfusion injury, and optimises a method of centrifugation of adult rat ventricular myocytes into a dense pellet to induce ischaemia, and simulate reperfusion by its dispersal. Remote preconditioning is evoked by preincubation of myocytes with serum samples taken from participants. This is used as a screening tool in order to test serum samples acquired from volunteers in control and disease states undergoing tourniquet ischaemia of a peripheral limb to reproduce the stimulus of remote preconditioning. A protective signal was seen in serum taken from healthy subjects following remote preconditioning versus baseline serum (20.5±3.3 vs 37.2±4.5 % necrosis respectively, n = 21, p < 0.001). Protection is absent in diabetes mellitus type 1 (51.5±4.6% necrosis, n = 14) and type 2 (51.3±8.2% necrosis, n = 10). The protective signal is preserved with age in healthy male participants, though appears to decline with age in a preliminary cohort of female participants. On assay of putative mechanisms of remote preconditioning, serum nitrite did not change with preconditioning in healthy volunteers, though it was found to significantly decrease in diabetes mellitus type 1. The implications for the application of this powerful yet elusive form of innate cardiac protection are considered.
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Vohra, Hunaid Ahmed. "Apoptosis and necrosis in ischaemia/reoxygenation injury of the human myocardium : mechanism of protection by ischaemic preconditioning." Thesis, University of Leicester, 2005. http://hdl.handle.net/2381/29881.
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Gene ChipRTM microarrays were used to analyse mRNA isolated from right atrial appendages (n=3/group) subjected to SI/R, IPC and caspase-3 inhibition. The initial studies were carried out with specific ischaemia/reoxygenation time-points. Apoptosis was shown to be greater than necrosis after 90min simulated ischaemia (SI) and 8h reoxygenation (R) but necrosis was greater than apoptosis by 24hr R. Inhibition of caspase-8+9 by z.IETD.fmk+z.LEHD.fmk (70nM) significantly reduced apoptosis following 90min SI and 2hr R and inhibition of caspase-3 by z.DEVD.fmk (70nM) almost completely abolished apoptosis, both without effecting necrosis. I have also shown that ischaemic preconditioning (IPC) is more efficacious in reducing apoptosis than necrosis. IPC inhibits necrosis in the human myocardium by signal transduction pathways that involve mitoKATP channels, PKC and p38MAPK. However, apoptosis that is inhibited by activation of mitoKATP channels and PKC is p38MAPK-independent. The observed changes in gene expression may help to understand the pathophysiology of ischaemic/reoxygenation injury and the mechanism of cardioprotection. With the information obtained in this thesis we have gained more information on the role of apoptosis in ischaemia/reperfusion injury of the human myocardium and a greater understanding of the underlying mechanisms and the signal transduction of cardioprotection by IPC. It is hoped that this knowledge will contribute to the design of therapeutical strategies that may reduce myocardial ischaeia/reperfusion injury in man.
15
McCarter, Jennifer F. "Inflammatory mechanisms in focal cerebral ischaemia." Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/28562.
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In this thesis, focal cerebral ischaemia was induced in three animal models in an attempt to investigate the contribution of the inflammatory response. The rat monofilament model of middle cerebral artery (MCA) occlusion, considered by some to be a pro-inflammatory model, was set up for the first time in Edinburgh and validated as suitable model for further investigation. Permanent and transient models were established to allow the evaluation of possible reperfusion injury. Both monofilament models were compared with the endothelin-1 model already established and routinely in use in the laboratory. Analysis of the volume of damage and distribution of the lesion revealed no differences between the three models. However this observation did not in itself rule out the possibility of different pathophysiological mechanisms in the three models that ultimately resulted in apparently similar sized lesions. FK506, a potent neuroprotectant widely used experimentally, exhibited different neuroprotective efficacies. In all models, FK506 significantly reduced the overall volume of both damage and oedema. The majority of the neuroprotection was observed in the cortex although striatal protection was seen in the transient rat monofilament model. The neuroprotection observed in the transient monofilament model was approximately twice that seen in the permanent model and similar to that in the endothelin-1 model suggesting distinct pathways that lead to cell death. Data for FK506 administration in the mouse monofilament model demonstrated neuroprotection for the first time in this species was included as an interesting comparison with the rat data. In summary, the re-introduction of blood to ischaemic tissue appears to alter the response of the individual cells although this does not change their ultimate fate. In instances where reperfusion is established, the tissue appears to be more amenable to neuroprotection by RK506. It is suggested that this is associated with the blockade of inflammatory mechanisms.
16
Mankad, Pankaj Shashikant. "Ischaemia-reperfusion injury and endothelial dysfunction." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392286.
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Coles, J. P. "Regional ischaemia following acute head injury." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597845.
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15Oxygen positron emission tomography (15O PET) has been used to demonstrate ischaemia and define physiological thresholds predictive of tissue viability in stroke. Unfortunately, it is difficult to translate such data to clinical head injury due to concurrent use of sedative agents, the metabolic effects of trauma, and the lack of a priori knowledge regarding the location of ischaemia. While ischaemia may be prominent in perilesional areas, it may also be observed in structurally normal brain. The methodological basis of 15O PET is discussed with consideration of the steady-state 15O model. These studies utilised phantom and control data to address the processing of imaging datasets, the precision of repeated measurements in interventional studies and the reliability of voxel-based measures of ischaemia. The methodology developed in these studies was used as a basis for the experimental work in patients. Head injured patients within 24 hours of ictus, showed evidence of regional ischaemia that was not detected by common bedside monitoring techniques, such as jugular bulb oximetry. Although the absolute volume of brain at risk was variable, it had important implications in terms of outcome. Evidence of an increased gradient for oxygen diffusion and impaired oxygen unloading were associated with structural evidence of microvascular collapse and perivascular oedema. This suggests that mechanisms other than simple perfusion-limited ischaemia may be responsible for tissue hypoxia in head injury. Moderate hyperventilation increased the volume of brain at risk of ischaemia injury, both by reducing perfusion, and by increasing oxygen demand. Brain regions that were unable to increase oxygen extraction to meet increased oxygen demand showed a fall in cerebral metabolism. Elevation of cerebral perfusion pressure above 70 mmHg does not benefit the injured brain in the absence of significant cerebral ischaemia.
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Kumar, Sanjeev. "Dexamethasome ameliorates ischaemia acute kidney injury." Thesis, Queen Mary, University of London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538661.
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Koo, Dicken D. H. "Ischaemia/reperfusion injury in renal transplantation." Thesis, University of Oxford, 1999. http://ora.ox.ac.uk/objects/uuid:e0177fd9-1504-4c76-b9fd-6e7ae0b6b466.
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Kidney transplants from both living-related (LRD) and living unrelated (LURD) donors have superior function and survival than transplants from cadaver donors. This may be unsurprising as kidneys from living donors are procured under optimal conditions, from healthy donors with minimal ischaemia times. In contrast, cadaver kidneys are obtained from traumatised donors and may experience extended periods of cold ischaemic storage before transplantation. An immunohistochemical analysis has been performed on biopsies obtained before, and immediately after transplantation, to investigate the potential causes of early inflammatory events associated with cadaver renal transplantation that may influence subsequent graft outcome. An immunohistochemical analysis of biopsies obtained before transplantation demonstrated upregulated expression of endothelial E-selectin and proximal tubular expression of ICAM-1, VCAM-1 and HLA Class II antigens in cadaver donor kidneys. Analysis of donor parameters demonstrated that traumatic physiological events experienced in intensive care around the time of brain death were significantly associated with the induction of proinflammatory antigens. Antigen induction in cadaver donor kidneys before transplantation was significantly associated with early acute rejection. Furthermore, in cadaveric kidneys with long cold ischaemia times, glomerular neutrophil infiltration and deposition of activated platelets expressing P-selectin on intertubular capillaries were detected following reperfusion, in association with impaired short and long term graft function. Expression of inflammatory mediators were absent in all LRD renal allografts before and after reperfusion. A clinical trial was performed to determine whether ischaemia/reperfusion injury may be ameliorated by reflushing cadaver kidneys after cold storage to remove harmful products that may have accumulated in the vessel lumen. Reflushing did not prevent the inflammatory events observed after reperfusion or improve graft function. Therefore, a novel, oxygen free radical scavenger (lec-SOD) was obtained to assess its potential efficacy in preventing ischaemia/reperfusion injury. Lec-SOD bound with high affinity to macro- and microvascular endothelial cells under cold hypoxic conditions following incorporation into Marshall's preservation solution, significantly inhibiting cold hypoxia induced cell death, adhesion molecule induction and neutrophil adhesion. Furthermore, preservation of kidneys with lec- SOD for 18 hr in an experimental model of chronic renal allograft rejection, significantly attenuated neutrophil infiltration and MHC Class I induction day 1 post-transplant, with improved long term renal function. The results presented in this Thesis demonstrate that donor factors and cold ischaemia/ reperfusion injury elicit an early inflammatory response that may influence graft outcome of cadaver kidneys. Refinements in donor management and organ preservation may limit the deleterious effects of ischaemia/reperfusion injury in cadaver renal allografts, increasing graft survival to that observed in living donor transplantation.
20
Yam, Philippa S. "Axonal injury following focal cerebral ischaemia." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298683.
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Lambiase, David Pier. "Myocardial adaptation to ischaemia in man." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408698.
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Cartaya, Rafael Eduardo Chavez. "Study on liver ischaemia and reperfusion." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388665.
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Fitridge, Robert Alwyn. "Reperfusion injury in focal cerebral ischaemia /." Title page, table of contents and abstract only, 1995. http://web4.library.adelaide.edu.au/theses/09MS/09msf546.pdf.
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Macaulay, Ewan. "Ischaemia-reperfusion during infrainguinal bypass for critical limb ischaemia and the effects of a nitric oxide donor." Thesis, University of Aberdeen, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301228.
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Hypothesis: That infrainguinal arterial bypass procedures are associated with an ischaemia-reperfusion injury and that this may be reduced by administration of sodium nitroprusside, a nitric oxide donor. First study: 28 subjects, with critical limb ischaemia, undergoing infrainguinal bypass were randomised to receive sodium nitroprusside (0.1 μg/kg body weight/min) (n=15) or placebo (n = 13), infused into the operated limb, during the performance of the second or distal anastomosis and the infusion continued for twenty minutes after. Blood sampling and a doppler studies were performed. 9 patients undergoing varicose vein operations were also examined. The results indicated that application of the proximal clamp resulted in ischaemia and reperfusion with associated neutrophil activation. Sodium nitroprusside resulted in vasodilatation but had no effect on either parameter. Bypass patients had higher baseline neutrophil activation than the varicose vein group. Second Study: 30 further bypass patients ere randomised (treatment n = 15, placebo n = 15) with the infusion commencing at the time of the proximal anastomosis. Blood and urine sampling and doppler studies were performed. Changes in plasma antioxidant status, microalbuminuria and enzymuria occurred only in the placebo group indicating that, in addition to vasodilating the critically ischaemic limb, the nitric oxide donor may have been protective. Paradoxically, myeloperoxidase levels rose only in the treatment group but there was no evidence of increased free radical activity or permeability changes associated with this. Conclusion: Infrainguinal bypass is associated with an ischaemia-reperfusion injury which begins at the time of first clamp application. These procedures also result in a small but significant decrease in antioxidants and an increase in permeability. Sodium nitroprusside, a nitric oxide donor, administered into the operated limb appears to be protective against these changes and is an effective peripheral vasodilator.
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Donaghy, Kevin M. "Actions of adenosine and anoxia in rat brain." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333806.
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Marie, Helene. "Proteins that interact with the sodium-dependent glutamate transporters." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341923.
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Ahmad, Maqsood. "Kinin peptides in the ischaemic myocardium." Thesis, University of Strathclyde, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248756.
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Murray, Katie. "Actions of interleukin-1 in cerebral ischaemia." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/actions-of-interleukin1-in-cerebral-ischaemia(76a8206b-4153-437d-9616-7d668a35db51).html.
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Cerebral ischaemia is characterised by an interruption in cerebral blood flow (CBF) leading to neuronal dysfunction and death. Pre-existing systemic inflammation is strongly associated with exaggerated brain injury following cerebral ischaemia with experimental studies showing that increased damage is mediated by interleukin (IL)-1 dependent pathways. The mechanisms through which systemic inflammation worsens stroke have yet to be elucidated, therefore in this thesis we sought to further determine how systemic inflammation affects outcome after acute cerebral ischaemia. The effects of acute pre-existing inflammation on cerebral perfusion and infarct volume after transient middle cerebral artery occlusion (MCAo) in rats were measured using magnetic resonance imaging (MRI). Systemic IL-1 caused a severe reduction in CBF and increase in infarct volume compared to vehicle. CBF changes were accompanied by upregulation of the vasoconstricting peptide endothelin (ET)-1. Blockade of ET-1 receptors reversed hypoperfusion, reduced ischaemic damage and improved functional outcome when assessed at 48h. Streptoccocus pneumoniae is the most common infection in patients at risk of stroke and is associated with an elevated inflammatory profile. The effect of an acute S. pneumoniae challenge on stroke outcome was assessed in mice and rats following transient MCAo. S. pneumoniae induced a systemic IL-1 response, exacerbated brain injury and increased platelet adhesion to the endothelium. Blockade of IL-1 with IL-1 receptor antagonist (IL-1Ra) and administration of glycoprotein (Gp) Ibα (to reduce platelet-endothelial interactions) reversed infection-mediated exacerbation of ischaemic injury and improved functional impairments after MCAo. Presence of chronic inflammation in the form of advanced age and obesity are associated with poorer outcomes following ischaemic stroke. The neuroprotective effects of delayed IL-1Ra on stroke outcome were assessed in aged lean and corpulent rats versus young rats at 7 days post-stroke. IL-1Ra reduced ischaemic damage, blood brain barrier (BBB) breakdown, improved functional outcomes and preserved neurogenesis in young and aged co-morbid rats at 24 hours and 7 days. Overall, these findings suggest systemic IL-1 is a common point of convergence in both acute and chronic pre-existing inflammatory disorders that are risk factors for stroke. Systemic IL-1 leads to excessive ischaemic damage through effects on the endothelium and the coagulation cascade. These results lend further support to the hypothesis that IL-1 is a potential therapeutic target in ischaemic stroke.
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Jones, Barney. "Ischaemia and efficiency in the isolated heart." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311982.
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Bradley, Peter Graham. "Pericontusional ischaemia following head injury : imaging correlates." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444637/.
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It has been well established that ischaemia can result in secondary injury to the brain following trauma. While such ischaemia has been imaged, it has been difficult demonstrate its physiological significance. The aim of this research was to use diffusion weighted magnetic resonance imaging (DWI) to characterise the patterns of cytotoxic and vasogenic oedema early after head injury and correlate changes with regional physiology, imaged using 150 positron emission tomography (,sO-PET). Data from methodological developments carried out in the course of this research are presented These include the testing of MR compatibility of infusion pumps, optimisation of image processing routines, assessment of the validity of commonly used MR measures of tissue injury in the context of head injury, and an assessment of the test-retest reproducibility of DWI. Early DWI imaging in 30 patients with significant head injury (range 8 - 134 hours) revealed a characteristic contusional morphology, with a haemorrhagic core and concentric rings of vasogenic and cytotoxic oedema. In the regions studied, the integrated volume of pericontusional oedema was over three times the volume of the central core. An analysis across patients, although confounded by interindividual variation, suggested that this pericontusional oedema increased in size with time from injury. Correlation with electron microscopy suggested microvascular ischaemia as a mechanism for these changes The physiological correlates of the ADC changes described above were investigated in a subset of nine patients with ,sO-PET. The contusion core showed significant reductions in cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral oxygen metabolism (CMR02), while the region of vasogenic oedema only showed significantly reductions in CMR02. Other studies explored the use of dynamic DWI to assess the impact of hyperventilation on ADC changes around contusions. The implications of these findings are discussed and further research directions explored.
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Thummachote, Mr Yongsuk. "The pathopysiological consequence of ischaemia reperfusion injury." Thesis, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498481.
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Bethell, H. W. L. "Potassium, acidosis and ventricular repolarisation during ischaemia." Thesis, University of Cambridge, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596607.
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In the first section the relative severity of the insult produced by low-flow ischaemia was established through a series of experiments monitoring the change in intracellular pH, high energy phosphates and LVDP during zero-flow, low flow (7.5% of the control flow rate) and moderate flow ischaemia (30% of the control flow rate). This established that in terms of mechanical performance and bioenergetic status reducing the flow to 7.5% of the control flow rate produced a significant ischaemic insult. Separate experiments showed that low-flow ischaemia caused action potential duration (APD) shortening which could be prevented by the KATP channel inhibitor glibenclamide, so implicating the KATP channel in the shortening process. In the second section it was established that low-flow ischaemia caused an early increase in 86Rb efflux which was maximal during the phase of APD shortening. Once again glibenclamide abolished APD shortening but only reduced the degree of 86Rb efflux. In the third section the effects of respiratory and metabolic acidosis, both known modulators of channel function, on the APD were investigated to establish whether they caused KATP channel activation in isolation in whole heart. In conclusion, this study has demonstrated that in whole heart low-flow ischaemia causes potassium efflux as a result of KATP channel activation, with the subsequent APD shortening. Intracellular acidosis and increased intracellular lactate, both known modulators of channel function in isolated patches, cause activation of the channel in isolation in whole heart but their main effect is to cause APD lengthening. Hence, these metabolic changes during ischaemia may serve to reduce overall APD shortening.
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Kinross, James M. "Systems metabolism of intestinal ischaemia/reperfusion injury." Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543342.
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Caldwell, Jane Cochrane. "Ventricular fibrillation in ischaemia and its defibrillation." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/6196/.
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ECG signals were recorded from isolated, Langendorff-perfused rabbit hearts to establish the relationship between dominant frequency and myocardial perfusion during ventricular fibrillation. Lower perfusion rates produced faster rates of dominant frequency decline, to lower steady state values. Optically mapping the anterior epicardial surface demonstrated heterogeneity of dominant frequency in ventricular fibrillation. During low-flow ischaemia, the dominant frequency reduction was restricted to the left ventricle. Application of individual ischaemic components during ventricular fibrillation demonstrated that raised [K+]EC, but not hypoxia or acidic pHEC, reproduced the ischaemic reduction of dominant frequency in the ECG, pseudoECG and over the left ventricular epicardial surface. In contrast, minimum defibrillation energies were increased by hypoxia and acidic pHEC, and not by raised [K+]EC. The dominant frequency heterogeneity during ventricular fibrillation in low-flow ischaemia and raised [K+]EC was not due to differential prolongation of repolarisation or post-repolarisation refractoriness in the left ventricle. Monophasic action potential studies showed that APD90 was reduced to similar degrees in each ventricle by low-flow ischaemia and raised [K+]EC. Effective refractory period was not altered in either ventricle by either condition. Low-flow ischaemia decreased conduction velocity in the left, but not the right ventricle. Conduction velocities were unaltered by raised [K+]EC in either ventricle. The activation threshold of the left ventricle was increased in low-flow ischaemia and raised [K+]EC, whilst the threshold of the right ventricle was unchanged. The increased activation threshold was associated with decreased upstroke velocity and diastolic depolarisation.
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Cooper, Marie. "An in-vitro assessment of myocardial ischaemia." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312386.
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McCaig, David. "Characterisation of Gadd34 response after cerebral ischaemia." Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433083.
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Crake, Thomas. "Myocardial ionic homeostasis during ischaemia and hypoxia." Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241332.
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Sitsapesan, R. "Opioid receptors and ischaemia-induced cardiac arrhythmias." Thesis, University of Strathclyde, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381536.
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Lee, Vee Meng. "Magnetic resonance imaging of cerebral ischaemia models." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242995.
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Selvam, Senthil. "The role of inflammation in retinal ischaemia." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10054093/.
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Purpose: The immune cascade is known to contribute to the pathology seen in oxygen induced retinopathy (OIR), however its exact role is poorly defined. We hypothesised that immune cell activation worsens hypoxia and exacerbates the neovascular sequelae seen in ischaemic retinopathy. Methods: We assess the effect of intraperitoneal lipopolysaccharide (IP LPS) injection in OIR mice. Neovascularisation was assessed by measuring the avascular area and neovascular tuft area at P17. Hypoxia was assessed using vessel tortuosity and EF5 hypoxia staining at P14. The activated retinal inflammatory cell population was characterised using immunohistochemistry and flow cytometry. Transgenic mice were bred to delete different subpopulations of inflammatory cells to define their role in hypoxia modulation. RNA sequencing performed on retinal tissue analysed the effect of systemic LPS on retinal cytokines and angiogenesis markers. Results: IP LPS injection at P12 in OIR mice significantly reduced neovascularisation at P17 and hypoxia at P14. Immunohistochemistry revealed an influx of round, CD11b+, lectin stained cells into the retina of LPS treated mice, which on flow cytometry were identified as myeloid cells, being predominantly Cd11b+Ly6Ghi neutrophils. Experimental depletion of the myeloid lineage was achieved using ROSA26eGFP-DTALysMcre, CCL2 and CCR2 knockout mouse lines and anti-CCR2 antibody MC21. However, when these mice were LPS treated, the effects on hypoxia readouts caused by LPS were still seen. Transcriptional profiling of the retina (using RNAseq) revealed a large upregulation in IL1β in the central, hypoxic retina of LPS treated mice. Injection of IL1β at P12 also mimicked the effects of LPS, suggesting that IL1β is a key mediator of the hypoxia reducing effect LPS has in the OIR model. Conclusions: These findings are counterintuitive to the current literature and provide new insight into the role the immune system has on regulating oxygen demand in the retina. This novel approach to reducing hypoxia has the potential to lead to novel therapies targeting hypoxia and preventing neovascularisation in ischaemic eye disease.
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Sheth, H. "Therapeutic modulation of liver ischaemia reperfusion injury." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1318134/.
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Liver Ischaemia Reperfusion Injury (IRI) leads to production of reactive oxygen species and cytokines, which affects hepatocellular function following liver resection and transplantation. This thesis examines 2 hypotheses: 1) The role of intravenous glycine in amelioration of liver IRI in a in vivo animal model of partial lobar liver IRI. 2) Does prophylactically administered N-acetylcysteine prevent liver IRI in patients undergoing elective liver resection. Materials and Methods 1) A rabbit model of hepatic lobar IRI was used to evaluate glycine. 3 groups (n=6) Sham group (laparotomy alone), ischaemia reperfusion (I/R) group (1 hour ischaemia and 6 hours of reperfusion), and glycine I/R group (IV glycine 5 mg/kg prior to the I/R protocol) were used. Portal blood flow, bile flow and bile was analysed by H1NMR spectroscopy. Hepatic microcirculation, intracellular tissue oxygenation, serum TNFα, IL-8, ALT, AST were measured at 1, 2, 4 and 6 hours following reperfusion. 2) A randomised double blind clinical trial was conducted to assess the effect of NAC on liver IRI following liver resections. The main outcomes were: morbidity and mortality, ICAM-1 expression in liver tissue, liver function tests. Patients were randomised to receive NAC as IV infusion (NACG) or a placebo group (PG) which received 5% dextrose only. Immunohistochemistry for ICAM-1 was carried out on perioperative liver biopsies. Results 1) Glycine normalised the bile flow, reduced phosphatidylcholine shedding, lactate surge, and stimulated bile acid, pyruvate, glucose and acetoacetate release. Glycine improved portal blood flow, hepatic microcirculation by the 2nd hour, and hepatic intracellular tissue oxygenation by the 4th hour of reperfusion. Glycine ameliorated serum TNFα at 1, 2 and 4 hours and serum Il- 8, AST and ALT up to 6 hours post reperfusion as compared to the I/R alone group. 2) Of the 43 patients, 15 received NAC, 16 were randomised to the PG, 12 were excluded due to inoperable tumours. Serum ALT was reduced in NACG (p=0.001), while serum ALP was higher in the NACG (p=0.003). ICAM-1 expression was up-regulated in 6/16 patients in the PG and in 3/15 patients in NACG. ICAM-1 was down-regulated in 1/15 patients in the NACG and none in the PG, the difference was not significant. Conclusions 1) Glycine ameliorated liver IRI, improved bile flow and composition. 2) NAC ameliorated parenchymal liver injury and enhanced liver regeneration in patients undergoing elective liver resection.
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Reddy, Mairi Helen. "Beta adrenergic function in acute myocardial ischaemia." Thesis, University of Edinburgh, 1989. http://hdl.handle.net/1842/19257.
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Du, Toit Johannes Marthinus. "Upper limb ischaemia : a twelve year experience." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/13136.
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Includes bibliographical references.Introduction: Upper limb ischaemia (ULI) is a relatively uncommon, but well recognized vascular entity. The sequalae of impaired function or amputation of an arm can be devastating to the individual with loss of independence and / or livelihood. There remains much to be learned that can only be established through good quality studies. This project was aimed at developing a comprehensive, but broad overview of ULI, specific to the population we serve. Aims: The objective was to review the Vascular Surgery Unit’s experience with ULI, with particular emphasis on defining the pattern and distribution of disease and pathological profile, describing key demographic and clinical features and reporting on conventional clinical outcomes. Areas of interest, with the potential for further research, were identified. Methods: Retrospective descriptive study. All patients that underwent a surgical intervention for ULI between January 2000 and December 2011, were included in the audit. Approval from the Department of Surgery Research Committee and Human Research Ethics Committee was obtained prior to accessing data (Appendix 1 & 2).A research folder was compiled for each patient. On completion of the data collection process, the findings were analyzed and compared to current literature on this topic. Results: Sixty-four patients with ULI were managed surgically during the 12 year study period. A male: female ratio of 0.60 (as opposed to 0.96 from 2011 Census figures), was reported. The thrombo-embolic subgroup of patients (n=30), were notably younger than expected (mean age of 55 years) compared to the UEAOD subgroup (n=12, mean age of 57 years). Approximately 48% were of mixed ethnicity, correlating well with 2011 Census figures. Referrals were predominately received from Secondary Hospitals (84%) situated within the Cape Metropole. 55% Presented with acute ULI, of which 40% were classified as Rutherford grade IIa and 17% diagnosed with established compartment syndrome. The majority of chronic ULI patients, presented with signs of tissue necrosis (48%).Other indications for intervention included upper extremity claudication symptoms (31%), rest pain (14%) as well as neuro-vascular symptoms (7%). A disproportionately high prevalence of cigarette smoking (83%,with an average of 31 pack years)was identified in the UEAOD subgroup. 27% Of patients were not receiving adequate pharmacological therapies aimed at addressing pre-existing risk factors, as proposed by the TASC II document. Thrombo-embolism was the single largest aetiological factor identified (47%),with the majority of occlusions (57%) occurring at the level of the brachial artery. A left-sided predominance with a ratio of 2:1, was noted. Approximately 47% of patients with UEAOD, were younger than 55 years. A clear proximal pattern of disease was observed (66% of lesions within the subclavian artery). Eighty-nine procedures were performed in 64 patients (78 open, 5 exclusively endovascular with a combined open / endovascular approach implemented in 6 patients). The 30-day mortality rate was 7.8%. Systemic complications were observed in 13% with 23% sustaining some form of procedural complication. Twenty amputations were performed in 64 patients, of which 6 were major amputations. The 30-day amputation rate after an attempt at revascularization, was 12.5%. Adherence to follow-up was poor (51% at 6 months), limiting interpretation of follow-up data. Conclusion: Although few firm conclusions could be drawn, this review has expanded our overall perspective of ULI, specific to the population we serve. It is anticipated that the publication of our institutional data will create a clinical awareness and facilitate future research projects in this field. A collaborative research effort between South African vascular units will facilitate comparison of different institutional experiences and enable pooled data analysis, perhaps further defining the pattern of upper limb vascular disease by identifying distinct geographical confounders.
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Laight, David W. "Neutrophils and vascular reactivity in ischaemia/reperfusion." Thesis, University of Bath, 1994. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385291.
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Mokhtarudin, Mohd Jamil Mohamed. "Mathematical modelling of cerebral ischaemia-reperfusion injury." Thesis, University of Oxford, 2016. http://ora.ox.ac.uk/objects/uuid:3f5dd7cf-e403-4cf0-b725-4ac235c1b37e.
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Restoring cerebral blood flow using reperfusion treatment is a common method in treating ischaemic stroke. Reperfusion treatment should be given within 4.5 hours from stroke onset. However, reperfusion beyond this time window poses the risk of reperfusion injuries such as intracranial haemorrhage and cerebral tissue swelling. The focus of this thesis is to study the effect of cerebral tissue swelling after reperfusion as it can occur in a few hours after the treatment. Cerebral tissue swelling may cause brain structure movement and cerebral microvessel compression; the latter may then lead to secondary ischaemia occurrence. In this thesis, two mathematical models are presented. The first model investigates the effect of ischaemia-reperfusion in the formation of cerebral tissue swelling. This model provides the understanding of suitable reperfusion conditions to reduce the effect of tissue swelling and also becomes the basis for the subsequent model. Meanwhile, the second model studies the role of a water-transporting protein, aquaporin-4 in ischaemia-reperfusion and its potential as part of treatments for cerebral tissue swelling. In addition, the ionic concentration may change during ischaemia which may be a factor contributing to cerebral tissue swelling. Thus, the effect of ionic concentration on the swelling formation is also investigated. Finally, validations of these models are achieved by developing patient-specific geometries from available ischaemic stroke patient MRI data and utilising finite element analysis. Comparison between the simulation results and the MRI data is done by quantifying the brain ventricles movement during cerebral tissue swelling.
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Dreier, Jens P. [Verfasser], Heiko [Gutachter] Luhmann, and Peter [Gutachter] Schmiedek. "Cortical spreading ischaemia and delayed ischaemic neurological deficits after subarachnoid haemorrhage / Jens P. Dreier ; Gutachter: Heiko Luhmann, Peter Schmiedek." Berlin : Humboldt-Universität zu Berlin, 2003. http://d-nb.info/1207667293/34.
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Dilly, S. G. "Electrophysical change in and around early myocardial ischaemia." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47029.
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Jönsson, Björn. "On leg ischaemia : aspects on epidemiology and diagnostics /." Linköping : Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med884s.pdf.
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Pathmanathan, Saidharshini. "Development of in vitro models of cerebral ischaemia." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249162.
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高榮華 and Weng-wah Wendy Ko. "Morphine treatment and acute myocardial ischaemia in rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1988. http://hub.hku.hk/bib/B31231172.
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