Title: The Cardioprotective Effect of Ischemic Preconditioning : Role of Adenosine and Protein Kinase C
Abstract:Background:Brief episodes of coronary blood flow interruption, ischemic preconditioning(IP), following a prolonged ischemia induces myocardial tolerance to ischemia and improves myocardial function du...Background:Brief episodes of coronary blood flow interruption, ischemic preconditioning(IP), following a prolonged ischemia induces myocardial tolerance to ischemia and improves myocardial function during reperfusion by undefined mechanism. Recently, it has been suggested that the signal transduction pathway of the cardiomyocyte itself may involve in this protection. The aims of the present study were:(1) to examine the effect of adenosine in early phase of IP, (2) to define the relationship between the adenosine and protein kinase C (PKC). Methods and Results:Hearts isolated from New Zealand White rabbit (1.2-1.5kg body weight, n=78) were perfused with Tyrode solution by non-recirculating Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to receiving 45min global ischemia (I) and 120min reperfusion (R) with or without IP. IP was induced by a single dose of 5min I and 10min R. A part of the IP hearts, calphostin C (200nmol/L), a PKC inhibitor, was administered 5min before IP and sustained during IP regimen. Left ventricular function and coronary flow were monitored. Infarct size was determined by staining with 1% triphenyltetrazolium chloride solution and computerized planimetry. Adenosine concentration in the coronary flow was determined by HPLC. Myocardial cytosolic and membrane PKC activities were measured by P-γ-ATP incorporation into PKC specific peptide. Expression of PKCe and PKCd was determined by SDSPAG-e and Western blot. IP enhanced improvement of functional recovery (p<0.05, in the left ventricular developed and end-Read More