Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486898
Title: The role of caspase inhibitors in protecting the myocardium from ischemia reperfusion injury
Author: Al-Rajaibi, Hajar M.
ISNI:       0000 0001 3407 9659
Awarding Body: Coventry University
Current Institution: Coventry University
Date of Award: 2008
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Abstract:
Rapid restoration of blood flow to ischemic myocardium is essential, however it causes further injury called reperfusion injury. Apoptosis contributes significantly to cardiomyocyte cell death during ischemia reperfusion injury, in which caspase family proteases play an essential role as they are the executioners of apoptosis. Caspase inhibitors showed promising cardioprotective results when administered before ischemia or at the start of reperfusion. However, before applying them in pre clinical studies of myocardial ischemia, several investigations needed to be taken to determine their therapeutic window post reperfusion, their effect on functional recovery of myocardium post ischemia, their mechanism of action. Methods Isolated perfused rat hearts were subjected to 35 min ischemia followed by 2 hr reperfusion where caspase inhibitors [broad spectrum caspase inhibitor (ZVAD, 0.1µM), specific caspase 3 inhibitor (DEVD, 0.07µM)] were added at the start of reperfusion, 15, 30 and 60 min after starting reperfusion at the presence or absence of Wortmannin (WORT, 100nM, PI3-kinase inhibitor). Hearts underwent triphenyl tetrazolium staining for infarct size assessment, or were frozen for Western blot analysis. Freshly isolated adult rat ventricular myocytes were subjected to 6 hr hypoxia followed by either 18 hr, where caspase inhibitors (ZVAD, 25µM and DEVD, 25µM) were added at the start of reoxygenation, 15, 30 and 60 min after starting reoxygenation at the presence or absence of Wortmannin (WORT, 100nM). Cardiomyocytes were analysed for viability, apoptosis, necrosis and intracellular caspase-3 activity using flow cytometry analysis. Isolated adult rat ventricular papillary muscles were subjected to 35 min hypoxia followed by 100 min reperfusion where caspase inhibitors [ZVAD (0.1 µM, 2.5µM) and DEVD (2.5µM)] were added at the start of reperfusion throughout. Power output was measured using work loop technique.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.486898  DOI: Not available
Keywords: Heart attack, heart injury, myocardium, infarction
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