Academic literature on the topic 'Ischaemic injury hearts'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Ischaemic injury hearts.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Ischaemic injury hearts"
1
Hill, Bradford G., Sunday O. Awe, Elena Vladykovskaya, Yonis Ahmed, Si-Qi Liu, Aruni Bhatnagar, and Sanjay Srivastava. "Myocardial ischaemia inhibits mitochondrial metabolism of 4-hydroxy-trans-2-nonenal." Biochemical Journal 417, no. 2 (December 23, 2008): 513–24. http://dx.doi.org/10.1042/bj20081615.
Full textAbstract:
Myocardial ischaemia is associated with the generation of lipid peroxidation products such as HNE (4-hydroxy-trans-2-nonenal); however, the processes that predispose the ischaemic heart to toxicity by HNE and related species are not well understood. In the present study, we examined HNE metabolism in isolated aerobic and ischaemic rat hearts. In aerobic hearts, the reagent [3H]HNE was glutathiolated, oxidized to [3H]4-hydroxynonenoic acid, and reduced to [3H]1,4-dihydroxynonene. In ischaemic hearts, [3H]4-hydroxynonenoic acid formation was inhibited and higher levels of [3H]1,4-dihydroxynonene and [3H]GS-HNE (glutathione conjugate of HNE) were generated. Metabolism of [3H]HNE to [3H]4-hydroxynonenoic acid was restored upon reperfusion. Reperfused hearts were more efficient at metabolizing HNE than non-ischaemic hearts. Ischaemia increased the myocardial levels of endogenous HNE and 1,4-dihydroxynonene, but not 4-hydroxynonenoic acid. Isolated cardiac mitochondria metabolized [3H]HNE primarily to [3H]4-hydroxynonenoic acid and minimally to [3H]1,4-dihydroxynonene and [3H]GS-HNE. Moreover, [3H]4-hydroxynonenoic acid was extruded from mitochondria, whereas other [3H]HNE metabolites were retained in the matrix. Mitochondria isolated from ischaemic hearts were found to contain 2-fold higher levels of protein-bound HNE than the cytosol, as well as increased [3H]GS-HNE and [3H]1,4-dihydroxynonene, but not [3H]4-hydroxynonenoic acid. Mitochondrial HNE oxidation was inhibited at an NAD+/NADH ratio of 0.4 (equivalent to the ischaemic heart) and restored at an NAD+/NADH ratio of 8.6 (equivalent to the reperfused heart). These results suggest that HNE metabolism is inhibited during myocardial ischaemia owing to NAD+ depletion. This decrease in mitochondrial metabolism of lipid peroxidation products and the inability of the mitochondria to extrude HNE metabolites could contribute to myocardial ischaemia/reperfusion injury.
2
Fernandez-Sanz, Celia, José Castellano, Elisabet Miro-Casas, Estefanía Nuñez, Javier Inserte, Jesús Vázquez, David Garcia-Dorado, and Marisol Ruiz-Meana. "Altered FoF1 ATP synthase and susceptibility to mitochondrial permeability transition pore during ischaemia and reperfusion in aging cardiomyocytes." Thrombosis and Haemostasis 113, no. 03 (May 2015): 441–51. http://dx.doi.org/10.1160/th14-10-0901.
Full textAbstract:
SummaryAging is a major determinant of the incidence and severity of ischaemic heart disease. Preclinical information suggests the existence of intrinsic cellular alterations that contribute to ischaemic susceptibility in senescent myocardium, by mechanisms not well established. We investigated the role of altered mitochondrial function in the adverse effect of aging. Isolated perfused hearts from old mice (> 20 months) displayed increased ischaemia-reperfusion injury as compared to hearts from adult mice (6 months) despite delayed onset of ischaemic rigor contracture. In cardiomyocytes from aging hearts there was a more rapid decline of mitochondrial membrane potential (ΔΨm) as compared to young ones, but ischaemic rigor shortening was also delayed. Transient recovery of ΔΨm observed during ischaemia, secondary to the reversal of mitochondrial FoF1 ATP synthase to ATPase mode, was markedly reduced in aging cardiomyocytes. Proteomic analysis demonstrated increased oxidation of different subunits of ATP synthase. Altered bionergetics in aging cells was associated with reduced mitochondrial calcium uptake and more severe cytosolic calcium overload during ischaemia-reperfusion. Despite attenuated ROS burst and mitochondrial calcium overload, mitochondrial permeability transition pore (mPTP) opening and cell death was increased in reperfused aged cells. In vitro studies demonstrated a significantly reduced calcium retention capacity in interfibrillar mitochondria from aging hearts. Our results identify altered FoF1 ATP synthase and increased sensitivity of mitochondria to undergo mPTP opening as important determinants of the reduced tolerance to ischaemia-reperfusion in aging hearts. Because ATP synthase has been proposed to conform mPTP, it is tempting to hypothesise that oxidation of ATP synthase underlie both phenomena.
3
Neckář, Jan, Adéla Boudíková, Petra Mandíková, Martin Štěrba, Olga Popelová, Ivan Mikšík, Ludmila Dabrowská, Jaroslav Mráz, Vladimír Geršl, and František Kolář. "Protective effects of dexrazoxane against acute ischaemia/reperfusion injury of rat hearts." Canadian Journal of Physiology and Pharmacology 90, no. 9 (September 2012): 1303–10. http://dx.doi.org/10.1139/y2012-096.
Full textAbstract:
Dexrazoxane (DEX), an inhibitor of topoisomerase II and intracellular iron chelator, is believed to reduce the formation of reactive oxygen species (ROS) and protects the heart from the toxicity of anthracycline antineoplastics. As ROS also play a role in the pathogenesis of cardiac ischaemia/reperfusion (I/R) injury, the aim was to find out whether DEX can improve cardiac ischaemic tolerance. DEX in a dose of 50, 150, or 450 mg·(kg body mass)–1 was administered intravenously to rats 60 min before ischaemia. Myocardial infarct size and ventricular arrhythmias were assessed in anaesthetized open-chest animals subjected to 20 min coronary artery occlusion and 3 h reperfusion. Arrhythmias induced by I/R were also assessed in isolated perfused hearts. Only the highest dose of DEX significantly reduced infarct size from 53.9% ± 4.7% of the area at risk in controls to 37.5% ± 4.3% without affecting the myocardial markers of oxidative stress. On the other hand, the significant protective effect against reperfusion arrhythmias occurred only in perfused hearts with the dose of DEX of 150 mg·kg–1, which also tended to limit the incidence of ischaemic arrhythmias. It is concluded that DEX in a narrow dose range can suppress arrhythmias in isolated hearts subjected to I/R, while a higher dose is needed to limit myocardial infarct size in open-chest rats.
4
GOODWIN, Andrew T., Mahboob A. KHAN, Adrian H. CHESTER, Mohamed AMRANI, and Magdi H. YACOUB. "Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest." Clinical Science 103, s2002 (September 1, 2002): 206S—209S. http://dx.doi.org/10.1042/cs103s206s.
Full textAbstract:
Endothelin-1 (ET-1) is believed to play an important role in cardiac ischaemia/reperfusion injury. ET-1 is synthesized from preproET-1 by the action of ET-converting enzyme (ECE). It is unclear to what extent the ET system is activated following prolonged ischaemia. In this study we used a model mimicking the conditions of the donor heart during transplantation. Isolated rat hearts perfused with Krebs–Henseleit buffer were subjected to 30min of normothermic perfusion, then 4h of cardioplegic arrest at 4°C with St Thomas' Hospital solution, followed by reperfusion for 2h. Hearts were freeze-clamped at different time points during the protocol. Using quantitative reverse transcription–PCR, relative levels of ET-1 and ECE mRNA expression were measured and compared with a housekeeping gene (ribosomal protein L32). During reperfusion there was a consistent decrease in coronary flow to approx. 85–90% of pre-ischaemic flow. There was no significant alteration in preproET-1 mRNA expression during 2h of reperfusion. However, ECE mRNA expression was increased by 77.5% at 1h and by 74.6% at 2h following ischaemia compared with pre-ischaemic values (P<0.05). Thus we conclude that ECE mRNA expression is increased following prolonged hypothermic cardioplegic arrest. Elevations in the expression of this enzyme may help to explain the role of the ET system in the pathogenesis of ischaemia/reperfusion injury following cardiac surgery and transplantation.
5
Sumegi, B., N. B. Butwell, C. R. Malloy, and A. D. Sherry. "Lipoamide influences substrate selection in post-ischaemic perfused rat hearts." Biochemical Journal 297, no. 1 (January 1, 1994): 109–13. http://dx.doi.org/10.1042/bj2970109.
Full textAbstract:
We investigated whether lipoamide and diacetyl-lipoamide are able to change the substrate selection in post-ischaemic myocardium. This can be important, because shifting heart metabolism from fatty acid to carbohydrate oxidation can decrease ischaemic injury. Studying the metabolism of [1,2-13C]diacetyl-lipoamide in situ in perfused rat heart by 13C n.m.r., we found intense 13C labelling in glutamate and aspartate, showing that acetyl groups from diacetyl-lipoamide are effectively transferred to CoA and metabolized in heart tissue. From analysis of glutamate C-3 and C-4 isotopomers, we determined the [1,2-13C]acetate/[3-13C]lactate utilization ratio in normoxic and post-ischaemic hearts, where under our experimental conditions the acetate/lactate utilization ratios were 1.2 +/- 0.2 and 2.4 +/- 0.3 in normoxic and post-ischaemic hearts respectively. When 0.25 mM lipoamide was added to the perfusate the acetate/lactate utilization ratio decreased to 1.4 +/- 0.1, which is almost equal to that found for normoxic hearts, showing that lipoamide increased the lactate utilization. In accordance with these data, we found that lipoamide activated pyruvate dehydrogenase by 50% in post-ischaemic myocardium. Competition between [3-13C]lactate and unlabelled octanoate was also studied in post-ischaemic hearts, and we found that lipoamide increased lactate utilization by 100% and increased the rate of the tricarboxylic acid cycle by 64%. Under the same experimental conditions, lipoamide significantly promoted the recovery of post-ischaemic unpaced hearts, showing the positive effect of increased lactate oxidation in post-ischaemic myocardium.
6
Brander, L., D. Weinberger, and C. Henzen. "Heart and Brain: A Case of Focal Myocytolysis in Severe Pneumococcal Meningoencephalitis with Review of the Contemporary Literature." Anaesthesia and Intensive Care 31, no. 2 (April 2003): 202–7. http://dx.doi.org/10.1177/0310057x0303100212.
Full textAbstract:
We report electrocardiographic changes mimicking myocardial ischaemia in a 73-year-old man with fatal pneumococcal meningoencephalitis, present the autopsy-confirmed histological picture of extensive focal myocytolysis (contraction band necrosis) without myocardial infarction or myocarditis, and review the contemporary literature. Potentially reversible, probably non-ischaemic myocardial dysfunction may occur in association with acute noncardiac illnesses, such as brain injuries. Biochemical and morphological abnormalities in acutely failing hearts from head-injured organ donors point to specific pathophysiological mechanisms, which are different from heart failure from other causes. Sepsis-related factors may add to the myocardial dysfunction in patients with brain injury from meningoencephalitis.
7
Uthman, Laween, Rianne Nederlof, Otto Eerbeek, Antonius Baartscheer, Cees Schumacher, Ninée Buchholtz, Markus W. Hollmann, Ruben Coronel, Nina C. Weber, and Coert J. Zuurbier. "Delayed ischaemic contracture onset by empagliflozin associates with NHE1 inhibition and is dependent on insulin in isolated mouse hearts." Cardiovascular Research 115, no. 10 (January 12, 2019): 1533–45. http://dx.doi.org/10.1093/cvr/cvz004.
Full textAbstract:
Abstract Aims Sodium glucose cotransporter 2 (SGLT2) inhibitors have sodium–hydrogen exchanger (NHE) inhibition properties in isolated cardiomyocytes, but it is unknown whether these properties extend to the intact heart during ischaemia–reperfusion (IR) conditions. NHE inhibitors as Cariporide delay time to onset of contracture (TOC) during ischaemia and reduce IR injury. We hypothesized that, in the ex vivo heart, Empagliflozin (Empa) mimics Cariporide during IR by delaying TOC and reducing IR injury. To facilitate translation to in vivo conditions with insulin present, effects were examined in the absence and presence of insulin. Methods and results Isolated C57Bl/6NCrl mouse hearts were subjected to 25 min I and 120 min R without and with 50 mU/L insulin. Without insulin, Empa and Cari delayed TOC by 100 and 129 s, respectively, yet only Cariporide reduced IR injury [infarct size (mean ± SEM in %) from 51 ± 6 to 34 ± 5]. Empa did not delay TOC in the presence of the NHE1 inhibitor Eniporide. Insulin perfusion increased tissue glycogen content at baseline (from 2 ± 2 µmol to 42 ± 1 µmol glycosyl units/g heart dry weight), amplified G6P and lactate accumulation at end-ischaemia, thereby decreased mtHKII and exacerbated IR injury. Under these conditions, Empa (1 µM) and Cariporide (10 µM) were without effect on TOC and IR injury. Empa and Cariporide both inhibited NHE activity, in isolated cardiomyocytes, independent of insulin. Conclusions In the absence of insulin, Empa and Cariporide strongly delayed the time to onset of contracture during ischaemia. In the presence of insulin, both Empa and Cari were without effect on IR, possibly because of severe ischaemic acidification. Insulin exacerbates IR injury through increased glycogen depletion during ischaemia and consequently mtHKII dissociation. The data suggest that also in the ex vivo intact heart Empa exerts direct cardiac effects by inhibiting NHE during ischaemia, but not during reperfusion.
8
van der Kraaij, A. M., J. F. Koster, and W. R. Hagen. "Reappraisal of the e.p.r. signals in (post)-ischaemic cardiac tissue." Biochemical Journal 264, no. 3 (December 15, 1989): 687–94. http://dx.doi.org/10.1042/bj2640687.
Full textAbstract:
The present study was designed to measure directly, using e.p.r. spectroscopy, oxygen-derived free radicals in (post)-ischaemic or (post)-anoxic rat hearts. Rat hearts were rapidly freeze-clamped at 77 K under normoxic, anoxic, ischaemic or reperfusion conditions. The samples were measured at three different temperatures (13, 77 and 115 K) and at several microwave power levels, and were compared with isolated rat heart mitochondria. Samples were prepared both by grinding and as tissue cuts. The two preparation techniques gave identical e.p.r. results, which excludes the occurrence of grinding artifacts. No free radical signals linked to reperfusion injury were detected. Several electron transfer centres known in the mitochondrial respiratory chain were measured. The signals previously assigned to post-ischaemic reperfusion injury were found to originate from electron transfer centres of the respiratory chain, predominantly the iron-sulphur cluster S-1 in succinate dehydrogenase. The differences in signal intensity between normoxic, ischaemic and reperfused hearts were found to result from the different redox stages of these centres under the various conditions tested. These findings do not necessarily imply that oxygen-derived free radicals are not formed in cardiac tissue during (post)-ischaemic reperfusion. The constitutive background of paramagnetism from the respiratory chain, however, seriously hampers the direct detection of comparatively low concentrations of free radicals in cardiac tissue. It is therefore expedient to focus future experiments in this field on the use of spin-trapping agents.
9
Solskov, Lasse, Bo Løfgren, Rasmus Pold, Steen B. Kristiansen, Torsten T. Nielsen, David H. Overstreet, Ole Schmitz, Hans Erik Bøtker, Sten Lund, and Gregers Wegener. "Evaluation of the relationship between hyperinsulinaemia and myocardial ischaemia/reperfusion injury in a rat model of depression." Clinical Science 118, no. 4 (November 9, 2009): 259–67. http://dx.doi.org/10.1042/cs20090108.
Full textAbstract:
Major depression is associated with medical co-morbidity, such as ischaemic heart disease and diabetes, but the underlying pathophysiological mechanisms remain unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to I/R (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning) in hearts from FSL rats using SD (Sprague–Dawley) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected or not to IPC before 40 min of global ischaemia, followed by 120 min of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats than in the SD rats following I/R injury (62.4±4.2 compared with 46.9±2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 h of fasting, but fasting plasma insulin (70.1±8.9 compared with 40.9±4.7 pmol/l; P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats had larger infarct sizes following I/R injury and were found to be hyperinsulinaemic compared with SD rats, but appeared to have a maintained cardioprotective mechanism against I/R injury, as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression.
10
Wang, Q. D., A. Swärdh, and P. O. Sjöquist. "Relationship between ischaemic time and ischaemia/reperfusion injury in isolated Langendorff-perfused mouse hearts." Acta Physiologica Scandinavica 171, no. 2 (February 19, 2001): 123–28. http://dx.doi.org/10.1046/j.1365-201x.2001.00788.x.
Full textDissertations / Theses on the topic "Ischaemic injury hearts"
1
Zatta, Amanda J., and n/a. "Adenosine and the Coronary Vasculature in Normoxic and Post-Ischaemic Hearts." Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20051130.124230.
Full textAbstract:
While previous research into the pathogenesis of ischaemic and reperfusion injuries has focussed on the cardiac myocyte, there is increasing evidence for a crucial role for coronary vascular injury in the genesis of the post-ischaemic phenotype [1-3]. Post-ischaemic vascular injury may be manifest as a transient or sustained loss of competent vessels, impairment of vascular regulatory mechanisms, and ultimately as the 'no-reflow' phenomenon (inability to sufficiently reperfuse previously ischaemic tissue despite the removal of the initial obstruction or occlusion). It is now appreciated that the earliest distinguishing feature of various forms of vascular injury (including atherosclerosis and infarction) is 'endothelial dysfunction', which is the marked reduction in endothelial-dependent relaxation due to reduced release or action of endothelial nitric oxide (NO). Importantly, vascular injury may worsen myocardial damage in vivo [4,5], significantly limiting tissue salvage and recovery. The pathogenesis of post-ischaemic vascular injury and endothelial dysfunction is incompletely understood, but has generally been considered to reflect a cardiovascular inflammatory response, neutrophils playing a key role. However, while blood-borne cells and inflammatory elements are undoubtedly involved in the 'progression' of vascular injury [6,7], accumulating evidence indicates that they are not the primary 'instigators' [8]. It should be noted that a wealth of controversial findings exists in the vascular injury literature and mechanisms involved remain unclear. Indeed, multiple mechanisms are likely to contribute to post-ischaemic vascular injury. Adenosine receptors are unique in playing a role in physical regulation of coronary function, and also in attenuating injury during and following ischaemia. While the adenosine receptor system has been extensively investigated in terms of effects on myocardial injury [9,10], little is known regarding potential effects of this receptor system on post-ischaemic coronary vascular injury. This thesis initially attempts to further our understanding of the role of adenosine in normal coronary vascular function, subsequent chapters assess the effect of ischaemia-reperfusion on vascular function, and adenosine receptor modification of vascular dysfunction in the isolated asanguinous mouse heart. Specifically, in Chapter 3 the receptor subtype and mechanisms involved in adenosine-receptor mediated coronary vasodilation were assessed in Langendorff perfused mouse and rat hearts. The study revealed that A2A adenosine receptors (A2AARs) mediate coronary dilation in the mouse vs. A2B adenosine receptors (A2BARs) in rat. Furthermore, responses in mouse involve a sensitive endothelial-dependent (NO-dependent) response and NO-independent (KATP-mediated) dilation. Interestingly, the ATP-sensitive potassium channel component predominates over NO-dependent dilation at moderate to high agonist levels. However, the high-sensitivity NO-dependent response may play an important role under physiological conditions when adenosine concentrations and the level of A2AAR activation are low. In Chapter 4 the mechanisms regulating coronary tone under basal conditions and during reactive hyperaemic responses were assessed in Langendorff perfused mouse hearts. The data support a primary role for KATP channels and NO in mediating sustained elevations in flow, irrespective of occlusion duration (5-40 s). However, KATP channels are of primary importance in mediating initial flow adjustments after brief (5-10 s) occlusions, while KATP (and NO) independent processes are increasingly important with longer (20-40 s) occlusion. Evidence is also presented for compensatory changes in KATP and/or NO mediated dilation when one pathway is blocked, and for a modest role for A2AARs in reactive hyperaemia. In Chapter 5 the impact of ischaemia-reperfusion on coronary function was examined, and the role of A1 adenosine receptor (A1AR) activation by endogenous adenosine in modifying post-ischaemic vascular function was assessed in isolated buffer perfused mouse hearts. The results demonstrate that ischaemia does modify vascular control and signficantly impairs coronary endothelial dilation in a model devoid of blood cells. Additionally, the data indicate that post-ischaemic reflow is significantly determined by A2AAR activation by endogenous adenosine, and that A1AR activation by endogenous adenosine protects against this model of vascular injury. Following from Chapter 5, the potential of A1, A2A and A3AR activation by exogenous and endogenous agonists to modulate post-ischaemic vascular dysfunction was examined in Chapter 6. Furthermore, potential mechanisms involved injury and protection were assessed by comparing effects of adenosine receptors to other 'vasoprotective' interventions, including anti-oxidant treatment, Na+/H+ exchange (NHE) inhibition, endothelin (ET) antagonism, and 2,3-butanedione monoxime (BDM). The data acquired confirm that post-ischaemic endothelial dysfunction is reduced by intrinsic A1AR activation, and also that exogenous A3AR activation potently reduces vascular injury. Protection appears unrelated to inhibition of ET or oxidant stress. However, preliminary data suggest A3AR vasoprotection may share signalling with NHE inhibition. Finally, the data reveal that coronary reflow in isolated buffer perfused hearts is not a critical determinant of cardiac injury, suggesting independent injury processes in post-ischaemic myocardium vs. vasculature. Collectively, these studies show that adenosine has a significant role in regulating coronary vascular tone and reactive hyperaemic responses via NO and KATP dependent mechanisms. Ischaemia-reperfusion modifies vascular control and induces significant endothelial dysfunction in the absence of blood, implicating neutrophil independent injury processes. Endogenous adenosine affords intrinsic vasoprotection via A1AR activation, while adenosinergic therapy via exogenous A3AR activation represents a new strategy for directly protecting against post-ischaemic vascular injury.
2
Zatta, Amanda J. "Adenosine and the Coronary Vasculature in Normoxic and Post-Ischaemic Hearts." Thesis, Griffith University, 2004. http://hdl.handle.net/10072/367305.
Full textAbstract:
While previous research into the pathogenesis of ischaemic and reperfusion injuries has focussed on the cardiac myocyte, there is increasing evidence for a crucial role for coronary vascular injury in the genesis of the post-ischaemic phenotype [1-3]. Post-ischaemic vascular injury may be manifest as a transient or sustained loss of competent vessels, impairment of vascular regulatory mechanisms, and ultimately as the 'no-reflow' phenomenon (inability to sufficiently reperfuse previously ischaemic tissue despite the removal of the initial obstruction or occlusion). It is now appreciated that the earliest distinguishing feature of various forms of vascular injury (including atherosclerosis and infarction) is 'endothelial dysfunction', which is the marked reduction in endothelial-dependent relaxation due to reduced release or action of endothelial nitric oxide (NO). Importantly, vascular injury may worsen myocardial damage in vivo [4,5], significantly limiting tissue salvage and recovery. The pathogenesis of post-ischaemic vascular injury and endothelial dysfunction is incompletely understood, but has generally been considered to reflect a cardiovascular inflammatory response, neutrophils playing a key role. However, while blood-borne cells and inflammatory elements are undoubtedly involved in the 'progression' of vascular injury [6,7], accumulating evidence indicates that they are not the primary 'instigators' [8]. It should be noted that a wealth of controversial findings exists in the vascular injury literature and mechanisms involved remain unclear. Indeed, multiple mechanisms are likely to contribute to post-ischaemic vascular injury. Adenosine receptors are unique in playing a role in physical regulation of coronary function, and also in attenuating injury during and following ischaemia. While the adenosine receptor system has been extensively investigated in terms of effects on myocardial injury [9,10], little is known regarding potential effects of this receptor system on post-ischaemic coronary vascular injury. This thesis initially attempts to further our understanding of the role of adenosine in normal coronary vascular function, subsequent chapters assess the effect of ischaemia-reperfusion on vascular function, and adenosine receptor modification of vascular dysfunction in the isolated asanguinous mouse heart. Specifically, in Chapter 3 the receptor subtype and mechanisms involved in adenosine-receptor mediated coronary vasodilation were assessed in Langendorff perfused mouse and rat hearts. The study revealed that A2A adenosine receptors (A2AARs) mediate coronary dilation in the mouse vs. A2B adenosine receptors (A2BARs) in rat. Furthermore, responses in mouse involve a sensitive endothelial-dependent (NO-dependent) response and NO-independent (KATP-mediated) dilation. Interestingly, the ATP-sensitive potassium channel component predominates over NO-dependent dilation at moderate to high agonist levels. However, the high-sensitivity NO-dependent response may play an important role under physiological conditions when adenosine concentrations and the level of A2AAR activation are low. In Chapter 4 the mechanisms regulating coronary tone under basal conditions and during reactive hyperaemic responses were assessed in Langendorff perfused mouse hearts. The data support a primary role for KATP channels and NO in mediating sustained elevations in flow, irrespective of occlusion duration (5-40 s). However, KATP channels are of primary importance in mediating initial flow adjustments after brief (5-10 s) occlusions, while KATP (and NO) independent processes are increasingly important with longer (20-40 s) occlusion. Evidence is also presented for compensatory changes in KATP and/or NO mediated dilation when one pathway is blocked, and for a modest role for A2AARs in reactive hyperaemia. In Chapter 5 the impact of ischaemia-reperfusion on coronary function was examined, and the role of A1 adenosine receptor (A1AR) activation by endogenous adenosine in modifying post-ischaemic vascular function was assessed in isolated buffer perfused mouse hearts. The results demonstrate that ischaemia does modify vascular control and signficantly impairs coronary endothelial dilation in a model devoid of blood cells. Additionally, the data indicate that post-ischaemic reflow is significantly determined by A2AAR activation by endogenous adenosine, and that A1AR activation by endogenous adenosine protects against this model of vascular injury. Following from Chapter 5, the potential of A1, A2A and A3AR activation by exogenous and endogenous agonists to modulate post-ischaemic vascular dysfunction was examined in Chapter 6. Furthermore, potential mechanisms involved injury and protection were assessed by comparing effects of adenosine receptors to other 'vasoprotective' interventions, including anti-oxidant treatment, Na+/H+ exchange (NHE) inhibition, endothelin (ET) antagonism, and 2,3-butanedione monoxime (BDM). The data acquired confirm that post-ischaemic endothelial dysfunction is reduced by intrinsic A1AR activation, and also that exogenous A3AR activation potently reduces vascular injury. Protection appears unrelated to inhibition of ET or oxidant stress. However, preliminary data suggest A3AR vasoprotection may share signalling with NHE inhibition. Finally, the data reveal that coronary reflow in isolated buffer perfused hearts is not a critical determinant of cardiac injury, suggesting independent injury processes in post-ischaemic myocardium vs. vasculature. Collectively, these studies show that adenosine has a significant role in regulating coronary vascular tone and reactive hyperaemic responses via NO and KATP dependent mechanisms. Ischaemia-reperfusion modifies vascular control and induces significant endothelial dysfunction in the absence of blood, implicating neutrophil independent injury processes. Endogenous adenosine affords intrinsic vasoprotection via A1AR activation, while adenosinergic therapy via exogenous A3AR activation represents a new strategy for directly protecting against post-ischaemic vascular injury.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
Full Text
3
Hack, Benjamin Daniel, and n/a. "Characterisation and Application of the Isolated Perfused Murine Heart Model and the Role of Adenosine and Substrate During Ischaemia-Reperfusion." Griffith University. School of Health Science, 2005. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20060810.144732.
Full textAbstract:
The Langendorff perfused murine heart has become an increasingly important research model in cardiovascular physiology and pharmacology. However, the model remains relatively poorly characterised when compared with the widely employed rat preparation. The purpose of the research within this thesis was initially two-fold: 1) to characterise the functional and substrate-dependent properties of the murine model; and 2) to characterise the relationships between glycolysis, ischaemic tolerance and adenosine-mediated cardioprotection in the mouse. Initial studies, confirmed by simultaneous/subsequent work in other laboratories, revealed the frequent occurrence of regular cyclic oscillations in contractile function and coronary flow in glucose-perfused isovolumically contracting hearts. This phenomenon (labelled 'cycling') was unaltered by inhibition of ?-adrenergic receptors, prostaglandins, and nitric oxide synthase. However, A1/A2 adenosine receptor agonism did abolish the oscillations in flow and reduced contractile oscillations by 50%. Importantly, cycling was eliminated by addition of 50 IU/l insulin to perfusion fluid, or provision of 5 mM pyruvate as a co-substrate with glucose. These data suggest that functional 'cycling' in glucose-perfused murine hearts likely occurs as a result of a mismatch between substrate metabolism (energy supply) and myocardial energy demand. It may be that glycolysis with exogenous glucose is insufficient to ensure appropriate matching of myocardial energy supply and demand. For this reason, it is advisable to employ a co-substrate such as pyruvate in studies of murine hearts. Further studies performed within this thesis generally employ this co-substrate addition. Addition of pyruvate as co-substrate removes 'cycling' but is also known to inhibit/modify glycolysis, which may affect ischaemic tolerance and/or cardioprotection mediated by adenosine. Experiments throughout this thesis demonstrated that pyruvate-perfusion improved tolerance to both ischaemia (delayed time to onset of ischaemic contracture; TOC) and reperfusion (reduced diastolic dysfunction and cell death). The delay in TOC as a result of pyruvate-perfusion also suggests that contracture is not solely influenced by anaerobic glycolysis (as outlined in current paradigms). To test the relevance of glycolysis to ischaemic injury hearts were subjected to various forms of glycolytic inhibition. Glycolysis was inhibited by use of 10 mM pyruvate, (iodoacetic acid) IAA treatment, and glycogen depletion by pre-ischaemic substrate-free perfusion (all groups employing pyruvate as sole-substrate). Each form of glycolytic modification resulted in significant delays in TOC, in complete contrast to findings from other models and species. Glycogen depletion also reduced the peak level of contracture. These findings indicate that the mouse is either unique in terms of substrate metabolism and mechanisms of contracture (an unlikely possibility), or raise serious questions regarding current models of contracture development during ischaemia (theorised to be delayed by prolonging anaerobic glycolysis). Modification of glycolysis also altered post-ischaemic outcome, with pyruvate perfusion and glycogen depletion both enhancing functional recoveries. However, IAA treated hearts, despite near-identical ischaemic tolerance (ie contracture development) to pyruvate-perfused hearts, displayed very poor functional recovery, which was below that for all other groups. These data clearly reveal that blocking glycolysis improves tolerance to ischaemia (as evidenced by reduced contracture), provide evidence of dissociation of ischaemic injury or contracture from post-ischaemic recovery, and confirm the key importance of glycolysis in enhancing recovery from ischaemia. Since tolerance to ischaemia/reperfusion was shown to be glycolysis dependent, and since it has been theorised that adenosine protects hearts through modulating glycolysis, the relationships between glycolytic inhibition and adenosine-mediated cardioprotection was tested. In a number of studies, exogenously applied adenosine was shown to protect both glucose- and pyruvate-perfused hearts (supporting no dependence of adenosinergic protection on glycolysis). However, to more equivocally test the role of glycolysis effects of IAA were studied and were shown to markedly limit protection with adenosine. The effects of adenosine during ischaemia were abolished by IAA treatment, and effects on post-ischaemic recovery were reduced (but not eliminated). Similar results were acquired for protection with endogenous adenosine (using iodotubercidin to block adenosine phosphorylation). Collectively, these data reveal that adenosinergic protection during ischaemia depends entirely upon glycolysis while protection during reperfusion likely involves glycolysis dependent and independent processes. However, glycolysis is required for full recovery of function during reperfusion. Further studies assessed the involvement of glycolysis in cardioprotection afforded by transgenic A1 adenosine receptor (A1AR) overexpression. It was found that pyruvate-perfusion provided the same protection as A1AR overexpression, and the two responses (to pyruvate and A1AR overexpression) were not additive. Thus, it is probable that common mechanisms are targeted in both responses (likely glycolysis). Finally, the effects of adenosine and pyruvate on oxidant injury were studied, testing whether interactions between adenosine and pyruvate observed in prior work within this thesis could be explained by alterations in anti-oxidant responses. It was found that adenosine has quite profound anti-oxidant responses in glucose-perfused hearts, with very selective effects on markers of damage. Pyruvate also had some anti-oxidant effects but interestingly it reduced the anti-oxidant effects of adenosine. In conclusion, the work entailed within this thesis demonstrates that the isolated mouse heart model may possess unique properties and should be further characterised by potential users in order to improve its utility, and the reliability of experimental findings (chiefly when studying ischaemia-reperfusion). Other work within thesis demonstrates that modification of glycolysis is important in dictating recovery from ischaemia-reperfusion, and also impacts on adenosine-mediated protection (principally but not exclusively during ischaemia itself). The manner in which glycolysis is modified and contributes to protection remains unclear.
4
Hack, Benjamin Daniel. "Characterisation and Application of the Isolated Perfused Murine Heart Model and the Role of Adenosine and Substrate During Ischaemia-Reperfusion." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/365760.
Full textAbstract:
The Langendorff perfused murine heart has become an increasingly important research model in cardiovascular physiology and pharmacology. However, the model remains relatively poorly characterised when compared with the widely employed rat preparation. The purpose of the research within this thesis was initially two-fold: 1) to characterise the functional and substrate-dependent properties of the murine model; and 2) to characterise the relationships between glycolysis, ischaemic tolerance and adenosine-mediated cardioprotection in the mouse. Initial studies, confirmed by simultaneous/subsequent work in other laboratories, revealed the frequent occurrence of regular cyclic oscillations in contractile function and coronary flow in glucose-perfused isovolumically contracting hearts. This phenomenon (labelled 'cycling') was unaltered by inhibition of ?-adrenergic receptors, prostaglandins, and nitric oxide synthase. However, A1/A2 adenosine receptor agonism did abolish the oscillations in flow and reduced contractile oscillations by 50%. Importantly, cycling was eliminated by addition of 50 IU/l insulin to perfusion fluid, or provision of 5 mM pyruvate as a co-substrate with glucose. These data suggest that functional 'cycling' in glucose-perfused murine hearts likely occurs as a result of a mismatch between substrate metabolism (energy supply) and myocardial energy demand. It may be that glycolysis with exogenous glucose is insufficient to ensure appropriate matching of myocardial energy supply and demand. For this reason, it is advisable to employ a co-substrate such as pyruvate in studies of murine hearts. Further studies performed within this thesis generally employ this co-substrate addition. Addition of pyruvate as co-substrate removes 'cycling' but is also known to inhibit/modify glycolysis, which may affect ischaemic tolerance and/or cardioprotection mediated by adenosine. Experiments throughout this thesis demonstrated that pyruvate-perfusion improved tolerance to both ischaemia (delayed time to onset of ischaemic contracture; TOC) and reperfusion (reduced diastolic dysfunction and cell death). The delay in TOC as a result of pyruvate-perfusion also suggests that contracture is not solely influenced by anaerobic glycolysis (as outlined in current paradigms). To test the relevance of glycolysis to ischaemic injury hearts were subjected to various forms of glycolytic inhibition. Glycolysis was inhibited by use of 10 mM pyruvate, (iodoacetic acid) IAA treatment, and glycogen depletion by pre-ischaemic substrate-free perfusion (all groups employing pyruvate as sole-substrate). Each form of glycolytic modification resulted in significant delays in TOC, in complete contrast to findings from other models and species. Glycogen depletion also reduced the peak level of contracture. These findings indicate that the mouse is either unique in terms of substrate metabolism and mechanisms of contracture (an unlikely possibility), or raise serious questions regarding current models of contracture development during ischaemia (theorised to be delayed by prolonging anaerobic glycolysis). Modification of glycolysis also altered post-ischaemic outcome, with pyruvate perfusion and glycogen depletion both enhancing functional recoveries. However, IAA treated hearts, despite near-identical ischaemic tolerance (ie contracture development) to pyruvate-perfused hearts, displayed very poor functional recovery, which was below that for all other groups. These data clearly reveal that blocking glycolysis improves tolerance to ischaemia (as evidenced by reduced contracture), provide evidence of dissociation of ischaemic injury or contracture from post-ischaemic recovery, and confirm the key importance of glycolysis in enhancing recovery from ischaemia. Since tolerance to ischaemia/reperfusion was shown to be glycolysis dependent, and since it has been theorised that adenosine protects hearts through modulating glycolysis, the relationships between glycolytic inhibition and adenosine-mediated cardioprotection was tested. In a number of studies, exogenously applied adenosine was shown to protect both glucose- and pyruvate-perfused hearts (supporting no dependence of adenosinergic protection on glycolysis). However, to more equivocally test the role of glycolysis effects of IAA were studied and were shown to markedly limit protection with adenosine. The effects of adenosine during ischaemia were abolished by IAA treatment, and effects on post-ischaemic recovery were reduced (but not eliminated). Similar results were acquired for protection with endogenous adenosine (using iodotubercidin to block adenosine phosphorylation). Collectively, these data reveal that adenosinergic protection during ischaemia depends entirely upon glycolysis while protection during reperfusion likely involves glycolysis dependent and independent processes. However, glycolysis is required for full recovery of function during reperfusion. Further studies assessed the involvement of glycolysis in cardioprotection afforded by transgenic A1 adenosine receptor (A1AR) overexpression. It was found that pyruvate-perfusion provided the same protection as A1AR overexpression, and the two responses (to pyruvate and A1AR overexpression) were not additive. Thus, it is probable that common mechanisms are targeted in both responses (likely glycolysis). Finally, the effects of adenosine and pyruvate on oxidant injury were studied, testing whether interactions between adenosine and pyruvate observed in prior work within this thesis could be explained by alterations in anti-oxidant responses. It was found that adenosine has quite profound anti-oxidant responses in glucose-perfused hearts, with very selective effects on markers of damage. Pyruvate also had some anti-oxidant effects but interestingly it reduced the anti-oxidant effects of adenosine. In conclusion, the work entailed within this thesis demonstrates that the isolated mouse heart model may possess unique properties and should be further characterised by potential users in order to improve its utility, and the reliability of experimental findings (chiefly when studying ischaemia-reperfusion). Other work within thesis demonstrates that modification of glycolysis is important in dictating recovery from ischaemia-reperfusion, and also impacts on adenosine-mediated protection (principally but not exclusively during ischaemia itself). The manner in which glycolysis is modified and contributes to protection remains unclear.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
Full Text
5
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.
Full textAbstract:
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.
6
Awad, Wael Ibrahim Issa. "Ischaemic preconditioning in the neonatal rat heart." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391636.
Full text
7
Kato, Rie. "Ischaemic injury in the heart : protective effects of anaesthetic agents." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343043.
Full text
8
Zhang, Liqun. "Effect of streptozotocin induced diabetes on the susceptibility of ex vivo rat heart." Thesis, University of Strathclyde, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248572.
Full text
9
Amrani, Mohamed. "Postischemic coronary flow and reperfusion injury." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307467.
Full text
10
Connaughton, Mark. "Aspects of ischaemia and reperfusion injury in the isolated rat heart." Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266208.
Full textBooks on the topic "Ischaemic injury hearts"
1
Giacca, Mauro, and Borja Ibáñez. Advanced therapies to treat cardiovascular diseases: controversies and perspectives. Edited by José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso, and Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0028.
Full textAbstract:
There is a pressing need to develop novel therapies for myocardial infarction and heart failure, two conditions that affect over 20% of the world population. Despite important advances in achieving revascularization of the ischaemic myocardium and the usefulness of devices in assisting failing hearts, therapy for these conditions remains poor. The final extent of myocardial tissue loss after infarction is a major determinant of post-infarction mortality due to heart failure. In this chapter we review the current strategies aimed at counteracting injury due to acute myocardial ischaemia–reperfusion and the experimental approaches to achieve cardiac and vascular regeneration once damage has occurred. We critically discuss the possibility of inducing tissue restoration by gene transfer or exogenous cell implantation, and report on the exciting possibility of stimulating the endogenous capacity of cardiac regeneration using growth factors and small regulatory RNAs.
2
Hausenloy, Derek, and Derek Yellon, eds. An Introduction to Cardioprotection. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199544769.003.0001.
Full textAbstract:
• In its broadest sense, the term ‘cardioprotection’ encompasses ‘all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage’• However, for the purposes of this book, the term ‘cardioprotection’ will refer to the endogenous mechanisms and therapeutic strategies that reduce or prevent myocardial damage induced by acute ischaemia-reperfusion injury• In this context, cardioprotection begins with the primary prevention of coronary heart disease and includes the reduction of myocardial injury sustained during coronary artery bypass graft surgery, and an acute myocardial infarction, conditions with considerable morbidity and mortality• An understanding of the pathophysiology of acute myocardial ischaemia-reperfusion injury is essential when designing new cardioprotective strategies• Several methods exist for both quantifying myocardial damage induced by acute ischaemia-reperfusion injury and for assessing myocardial salvage following the application of cardioprotective strategies• Importantly, novel cardioprotective strategies must be capable of preventing and reducing myocardial damage over and above that provided by current optimal therapy.
3
Barnard, Matthew, and Nicola Jones. Intensive care management after cardiothoracic surgery. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0368.
Full textAbstract:
Management of the post-cardiothoracic surgical patient follows general principles of intensive care, but incorporates certain unique considerations. In cardiac surgical patients peri-operative ischaemia, arrhythmias and ventricular dysfunction mandate specific monitoring requirements, and individual pharmacological and mechanical support. Suspicion of myocardial ischaemia should not only lead to pharmacological treatment, but also consideration of urgent angiography to exclude coronary graft occlusion. Ventricular dysfunction may be pre-existing or attributable to intra-operative myocardial ‘stunning’. Catecholamines and phosphodiesterase inhibitors are the mainstay of therapy. Rarely, intra-aortic balloon pumping or ventricular assist devices are required. Significant bleeding (with potential cardiac tamponade), respiratory compromise, acute kidney injury, neurological injury, and deep sternal wound infection each occur in ~2–3% of cardiac surgical patients. Each of these has individual risk factors and specific management considerations. General guidelines for patients who have undergone thoracic surgery include early extubation, fluid restriction, effective analgesia, and protective lung ventilation. Thoracic patients are at risk of atelectasis, respiratory infection, bronchial air leak, and right ventricular failure. Positive pressure ventilation is avoided whenever possible particularly after pneumonectomy, but is sometimes necessary in compromised patients. Air leaks are common. Alveolopleural fistulae usually improve with conservative management,whereas bronchopleural fistulae are more likely to require surgical intervention. Lung surgery is high risk for patients with ischaemic heart disease. Patients with pre-existing elevated pulmonary vascular resistance may exhibit right ventricular dysfunction and may fail to cope with a further increase in pulmonary vascular resistance consequent to lung resection. Lung collapse and infection are constant risks throughout the entire post-operative period.
4
Vimalesvaran, Kavitha, and Michael Marber. Myocardial Remodelling after Myocardial Infarction. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199653461.003.0031.
Full textAbstract:
This chapter focuses on myocardial remodelling, a process that affects the heart’s shape, structure, and function, following myocardial injury (MI). Post-MI remodelling can be divided into three phases, with the first phase 0–72 hours beginning at the time of ischaemic injury, the second phase 72 hours to 6 weeks, and the third and last phase 6 weeks and beyond. During post-infarction remodelling, hypertrophy is an adaptive response that compensates for the increased load, reduces the effect of progressive dilatation, and balances contractile function. The chapter discusses the factors involved in ventricular remodelling and its association with heart failure progression. The effects of therapies designed to prevent or attenuate post-infarction left ventricular remodelling, with reference to the pathophysiological mechanisms involved, are then considered. Therapies specifically discussed include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β-adrenoreceptor blockers, and aldosterone receptor antagonists.
5
Jumean, Marwan F., and Mark S. Link. Post-cardiac arrest arrhythmias. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0065.
Full textAbstract:
Our understanding of arrhythmias following resuscitated cardiac arrest has evolved over the past two decades to entail complex pathophysiological processes including, in part, ischaemia and ischaemia-reperfusion injury. Electrical instability after the return of spontaneous circulation (ROSC) is common, ranging from atrial fibrillation to recurrent ventricular tachycardia and fibrillation. Electrical instability following out-of-hospital cardiac arrest is most commonly due to myocardial ischaemia and post-arrest myocardial dysfunction. However, electrolyte disturbances, elevated catecholamine levels, the frequent use of vasopressors and inotropes, and underlying structural heart disease or channelopathies also contribute in the acute setting. Limited data exists that specifically address the management of arrhythmias in the immediate post-arrest period. In addition to treating any potential reversible cause, the management in the haemodynamically-stable patient includes beta-blockers, class I (lignocaine and procainamide) and III anti-arrhythmic agents (amiodarone). Defibrillation is often needed for recurrent ventricular arrhythmias.
6
Hausenloy, Derek, and Derek Yellon, eds. Novel Cardioprotective Strategies. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199544769.003.0011.
Full textAbstract:
• Despite optimal therapy, the mortality and morbidity of coronary heart disease remains significant. Hence, novel treatment strategies of cardioprotection are required to improve clinical outcomes in these patients• Experimental studies have provided a plethora of therapeutic strategies for reducing myocardial injury, but the translation of these findings into the clinical setting has been largely disappointing. Many of these unsuccessful clinical studies have relied upon individually targeting established mediators of lethal reperfusion injury such as oxidative stress, inflammation, calcium overload and so forth• Clearly, novel targets for cardioprotection as well as a multi-targeted approach to cardioprotection directed against the multiple causes of lethal reperfusion injury are required to effect benefits in clinical outcomes• In this regard, the introduction of ischaemic postconditioning, a novel treatment strategy, in which following primary PCI the process of myocardial reperfusion is interrupted by several coronary re-occlusions, has been reported to reduce myocardial myocardial injury in AMI patients• Furthermore, experimental studies have identified the Reperfusion Injury Salvage Kinase (RISK) pathway and the mitochondrial permeability transition pore (mPTP) as novel targets for cardioprotection, which are currently been examined in the clinical setting.
7
Rady, Mohamed Y., and Ari R. Joffe. Non-heart-beating organ donation. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0390.
Full textAbstract:
The transplantation community endorses controlled and uncontrolled non-heart-beating organ donation (NHBD) to increase the supply of transplantable organs at end of life. Cardiac arrest must occur within 1–2 hours after the withdrawal of life-support in controlled NHBD. Uncontrolled NHBD is performed after failed cardiopulmonary resuscitation in an unexpected witnessed cardiac arrest. Donor management aims to protect transplantable organs against warm ischaemic injury through the optimization of haemodynamics and mechanical ventilation. This also requires antemortem instrumentation and systemic anticoagulation for organ perseveration in controlled NHBD. Interval support with extracorporeal membrane oxygenation or cardiopulmonary bypass is generally required for optimal organ perfusion and oxygenation in uncontrolled NHBD, which remains a controversial medical practice. There are several unresolved ethical challenges. The circulatory criterion of 2–10 minutes of absent arterial pulse does not comply with the uniform determination of death criterion of the irreversible cessation of functions of the cardiovascular or central nervous systems. There are no robust safeguards in clinical practice that can prevent faulty prognostication, and premature withdrawal of treatment or termination of cardiopulmonary resuscitation. Unmanaged conflicting interests of increasing the supply of transplantable organs can have serious consequences on the medical care of potentially salvageable patients. Perimortem interventions can interfere with the delivery of an optimal quality of end-of-life care. The lack of disclosure of these NHBD ethical controversies does not uphold the moral obligation for an informed consent.
8
Ho, Vanessa P., and Philip S. Barie. Acute acalculous cholecystitis in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0188.
Full textAbstract:
Acute acalculous cholecystitis (AAC) may occur in surgical or injured, critically-ill, and systemically-ill patients, with diabetes mellitus, malignant disease, abdominal vasculitis, congestive heart failure, cholesterol embolization, shock, and cardiac arrest. Children may also be affected, especially following a viral illness. The pathogenesis of AAC is complex and multifactorial. Ischaemia/reperfusion injury and the associated pro-inflammatory response and oxidative tissue stress, appear to be the central mechanisms, but bile stasis, opioid therapy, positive-pressure ventilation, and parenteral nutrition may all contribute to development of the disease. Ultrasound of the gallbladder is most accurate for the diagnosis of AAC in the critically-ill patient. Computed tomography is probably of comparable accuracy, but carries both advantages and disadvantages. Percutaneous cholecystostomy is now the treatment of choice, controlling AAC in about 85% of patients, despite the known high prevalence of gallbladder infarction (~50%) and perforation (~10%). Rapid improvement may be expected when AAC is diagnosed correctly and cholecystostomy is performed timely. The mortality (historically ~30%) of percutaneous and open cholecystostomy are similar, reflecting the severity of illness, but improved resuscitation and critical care may portend a decreased risk of death.
9
Bouchama, Abderrezak. Pathophysiology and management of hyperthermia. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0353.
Full textAbstract:
Hyperthermia is a state of elevated core temperature that rises rapidly above 40°C, secondary to failure of thermoregulation. Hyperthermia has many causes, but it is the hallmark of three conditions—heatstroke, malignant hyperthermia, and neuroleptic malignant syndrome. The clinical and metabolic alterations of hyperthermia, if left untreated, can culminate in multiple organ system failure and death. High temperature causes direct cellular death and tissue damage. The extent of tissue injury is a function of the degree and duration of hyperthermia. Heat-induced ischaemia-reperfusion injury, and exacerbated activation of inflammation and coagulation are also contributory. Hyperthermia is a true medical emergency with rapid progression to multiple organ system failure and death. The primary therapeutic goal is to reduce body temperature as quickly as possible using physical cooling methods, and if indicated, the use of pharmacological treatment to accelerate cooling. There is no evidence of the superiority of one cooling technique over another. Non-invasive techniques that are easy to use and well-tolerated are preferred. Pharmacological cooling with Dantrolene sodium is crucial in the treatment of malignant hyperthermia.
10
Ramsay, Michael A. E. Anaesthesia for transplant surgery. Edited by Philip M. Hopkins. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0067.
Full textAbstract:
The provision of anaesthesia for organ transplantation requires a team of specialist anaesthetists who are available 24 hours a day. The cold and warm ischaemia times may have very deleterious effects on the graft. The team must have a basic understanding of the immune system and the strategies of immunosuppression therapy. The preoperative assessment of the patient requires an understanding of the cause and effects of the compromised organ that is to be replaced. The procedure in many instances will result in a reperfusion syndrome when the graft is revascularized and also an ischaemia–reperfusion injury. The understanding of these entities is essential as is the preparation and protocols to treat or ameliorate the effects of these syndromes if they occur. The preparation for many organ transplants includes invasive monitoring of haemodynamics, cardiac function, pulmonary function, and acid–base balance. Access for massive transfusion therapy and coagulation assessment is essential for many transplant procedures. The maintenance of body temperature and fluid balance may be challenging. The protection and monitoring of the function of major organs such as the brain, heart, lungs, and kidneys is essential but the homeostasis of endocrine function and electrolytes is also important. The provision of excellent anaesthesia is a key component of a successful transplant programme. A small team of highly trained professionals with extensive training and experience in transplant anaesthesia provide the best results.
Book chapters on the topic "Ischaemic injury hearts"
1
Verkleij, A. J., and J. A. Post. "Physico-chemical properties and organization of lipids in membranes: their possible role in myocardial injury." In Lipid metabolism in the normoxic and ischaemic heart, 85–91. Heidelberg: Steinkopff, 1987. http://dx.doi.org/10.1007/978-3-662-08390-1_10.
Full text
2
Piper, H. M., and A. Das. "Detrimental actions of endogenous fatty acids and their derivatives. A study of ischaemic mitochondrial injury." In Lipid metabolism in the normoxic and ischaemic heart, 187–96. Heidelberg: Steinkopff, 1987. http://dx.doi.org/10.1007/978-3-662-08390-1_23.
Full text
3
Krause, Ernst-Georg, Georg Rabitzsch, Franz Noll, Johannes Mair, and Bernd Puschendorf. "Glycogen phosphorylase isoenzyme BB in diagnosis of myocardial ischaemic injury and infarction." In Biochemical Mechanisms in Heart Function, 289–95. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4613-1279-6_37.
Full text
4
Halestrap, A. P., C. P. Connern, E. J. Griffiths, and P. M. Kerr. "Cyclosporin A binding to mitochondrial cyclophilin inhibits the permeability transition pore and protects hearts from ischaemia/reperfusion injury." In Detection of Mitochondrial Diseases, 167–72. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4615-6111-8_25.
Full text
5
"Interventional cardiology for coronary heart disease." In Oxford Handbook of Cardiac Nursing, edited by Kate Olson, 137–60. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199651344.003.0008.
Full textAbstract:
Interventional cardiology is concerned with a number of invasive diagnostic and interventional procedures including coronary angiography and percutaneous coronary intervention (PCI). Coronary angiography is a definitive test to diagnose the presence of absence of coronary artery disease, in addition to nonatherosclerotic causes of stable angina, such as coronary artery spasm. PCI is a term that collectively describes a group of procedures that aim to restore or improve blood flow to the myocardium following a period of ischaemia or injury and includes: percutaneous transluminal coronary angioplasty (PTCA), intracoronary stenting, coronary atherectomy, and thrombectomy devices. The aim of this chapter is to provide a description, indications, and pre- and postprocedure care related to common diagnostic and interventional cardiology procedures. Sheath removal and vascular closure devices are also discussed.
6
Perera, Jonathan, and Marco Sinisi. "Supraclavicular brachial plexus and peripheral nerve injuries." In Oxford Textbook of Neurological Surgery, edited by Ramez W. Kirollos, Adel Helmy, Simon Thomson, and Peter J. A. Hutchinson, 847–54. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780198746706.003.0073.
Full textAbstract:
Stretching of more than 12% of a nerve or more than 8 hours of ischaemia will result in severe nerve injury. The force required to avulse cervical nerve roots is as little as 200 newtons. The nerve root exiting angles are very important, as different forequarter positions at the time of impact will result in differing force vectors and therefore differing injury. Nerve injuries can be extremely devastating not only for the patient but for their surrounding support structure as well. We discuss and detail the diagnosis and management of these lesions along with the useful investigations and treatment options. The appropriately timed management of these patients can allow good outcomes for both patient physical and subsequent mental health.
7
Kalra, P. A., and J. D. Firth. "Atherosclerotic renovascular disease." In Oxford Textbook of Medicine, 4078. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.211009_update_002.
Full textAbstract:
Atherosclerotic renovascular disease (ARVD) refers to atheromatous narrowing of one or both renal arteries and frequently co-exists with atherosclerotic disease in other vascular beds. Patients with this condition are at high risk of adverse cardiovascular events, with mortality around 8% per year. Many patients with ARVD have chronic kidney disease, but only a minority progress to end-stage kidney disease (ESKD), suggesting that pre-existing hypertensive and/or ischaemic renal parenchymal injury is the usual cause of renal dysfunction. Many patients with ARVD are asymptomatic, but there can be important complications such as uncontrolled hypertension, rapid decline in kidney function and recurrent acute heart failure (flash pulmonary oedema)....
8
Arends, Mark J., and Christopher D. Gregory. "Apoptosis in health and disease." In Oxford Textbook of Medicine, edited by John D. Firth, Christopher P. Conlon, and Timothy M. Cox, 266–80. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0034.
Full textAbstract:
Apoptosis is the process by which single cells die in the midst of living tissues. It is responsible for most—perhaps all—of the cell death events that occur during the formation of the early embryo and the sculpting of organs. Apoptotic cell death continues to play a critical role in the maintenance of cell numbers in those tissues in which cell turnover persists into adult life, such as the epithelium of the gastrointestinal tract, the bone marrow, and lymphoid system including both B- and T-cell lineages. This chapter gives an overview of apoptosis in health and disease. Apoptosis appears in the reactions of many tissues to injury, including mild degrees of ischaemia, exposure to ionizing and ultraviolet radiation, or treatment with cancer chemotherapeutic drugs. Excessive or too little apoptosis play a significant part in the pathogenesis of autoimmunity, infectious disease, AIDS, stroke, myocardial disease, and cancer.
9
Bakaeen, Faisal G., and Lars G. Svensson. "Redo coronary artery bypass grafting." In State of the Art Surgical Coronary Revascularization, edited by Joseph F. Sabik, Stuart J. Head, and Vipin Zamvar, 369–74. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198758785.003.0064.
Full textAbstract:
Patients who undergo redo coronary artery bypass grafting (CABG) are older, have more comorbidities, and a greater atherosclerotic burden than those who undergo primary CABG. In addition, redo CABG is technically more demanding than primary CABG. Sternal re-entry may be challenging because of the proximity of cardiovascular structures, including previous bypass grafts that could be at risk for injury. Furthermore, dissecting out the heart to institute cardiopulmonary bypass and exposing the coronary targets may be complicated by scar tissue and suboptimal dissection planes, with additional risk of injury to patent conduits or inadvertent manipulation of diseased conduits that can result in thromboembolic complications and ischaemia. Effective myocardial protection is especially important in redo CABG, and anatomical limitations must be overcome in patients with severe diffuse native disease or areas supplied by occluded grafts. Patent left internal thoracic arteries in redo CABG patients introduce an extra level of complexity in intraoperative management.
10
Wyllie, Andrew H., and Mark J. Arends. "Apoptosis in health and disease." In Oxford Textbook of Medicine, 177–88. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.0406.
Full textAbstract:
Apoptosis is the process by which single cells die in the midst of living tissues. It is responsible for most—perhaps all—of the cell-death events that occur during the formation of the early embryo and the sculpting and moulding of organs. Apoptotic cell death continues to play a critical role in the maintenance of cell numbers in those tissues in which cell turnover persists into adult life, such as the epithelium of the gastrointestinal tract, the bone marrow, and lymphoid system including both B- and T-cell lineages. Apoptosis is the usual mode of death in the targets of natural killer (NK) cells and cytotoxic T-cells, and in involution and atrophy induced by hormonal and other stimuli. It also appears in the reaction of many tissues to injury, including mild degrees of ischaemia, exposure to ionizing and ultraviolet radiation, or treatment with cancer chemotherapeutic drugs. Excessive or too little apoptosis play a significant part in the pathogenesis of autoimmunity, infectious disease, AIDS, stroke, myocardial disease, and cancer. When cancers regress, apoptosis is part of the mechanism involved. Here the cellular processes and molecular mechanisms of apoptosis are set out, together with a conspectus of its involvement in many diseases....
Conference papers on the topic "Ischaemic injury hearts"
1
Warpsinski, Gabriela, Salil Srivastava, Thomas P Keeley, Paul Fraser, and Giovanni E Mann. "17 Establishing a physiologically relevant in vitro model for ischaemic stroke injury in brain endothelial cells." In Abstracts from the Fellowship of Postgraduate Medicine Centenary Conference 2018: Transforming Health and Health Care. The Fellowship of Postgraduate Medicine, 2018. http://dx.doi.org/10.1136/postgradmedj-2018-fpm.28.
Full text
2
Lim, Ven Gee, Sapna Arjun, Robert Bell, and Derek Yellon. "BS10 Canagliflozin, an SGLT2 inhibitor attenuates ischaemia/reperfusion injury in the non-diabetic heart." In British Cardiovascular Society Annual Conference ‘Digital Health Revolution’ 3–5 June 2019. BMJ Publishing Group Ltd and British Cardiovascular Society, 2019. http://dx.doi.org/10.1136/heartjnl-2019-bcs.174.
Full text
3
Draganova, Lilia, Rachael Redgrave, Simon Tual-Chalot, Sarah Marsh, Helen Arthur, and Ioakim Spyridopoulos. "BS31 The role of fractalkine and CX3CR1-expressing lymphocytes during myocardial ischaemia/reperfusion injury." In British Cardiovascular Society Annual Conference ‘Digital Health Revolution’ 3–5 June 2019. BMJ Publishing Group Ltd and British Cardiovascular Society, 2019. http://dx.doi.org/10.1136/heartjnl-2019-bcs.194.
Full text