Calpain Inhibitors and Modulation of Ischaemia Reperfusion Induced Apoptosis and Necrotic Myocardial Cell Injury

Apoptosis is a crucial event that can initiate ischaemia-reperfusion induced inflammation and subsequent tissue injury. Myocardial ischaemia reperfusion is associated with activation of intracellular death proteases known as calpains. Myocardial ischaemia was induced in isolated rat heart which was subjected to 30 min ischaemia followed by reperfusion for 120min. The effect of calpain inhibitors SJA7019 and SJA 7029(10μM and 15μM) in induced myocardial injury assessed in terms of infract size measured macroscopically, release of LDH and CK have been investigated. Agarose gel electrophoresis was used to assess the DNA smearing. TUNEL staining was done to investigate the apoptotic index. Calpain inhibitors such as SJA7019 and SJA7029 has attenuated ischaemia reperfusion induced increase in LDH,CK, myocardial infarct size ,DNA smearing and apoptotic index. In the present study it is concluded that inhibition of intracellular death proteases prevented ischaemia reperfusion induced apoptosis induced necrotic cell death. Keyword: Apoptosis, Calpain, Ischaemia-reperfusion induced myocardial injury, Necrosis