CARDIAC PRECONDITIONING WITH CALCIUM - CLINICALLY ACCESSIBLE MYOCARDIAL PROTECTION

Cardiac preconditioning is mediated by protein kinase C. Although endo genous calcium is a potent stimulus of protein kinase C, it remains un known whether preischemic administration of exogenous calcium can indu ce protein kinase C-mediated myocardial protection against ischemia-re perfusion injury. To study this, calcium chloride was administered ret rogradely through the aorta at a rate 5 nmol/min for 2 minutes to isol ated perfused rat hearts 10 minutes before a 20-minute ischemia and 10 -minute reperfusion insult, Calcium-mediated cardioadaptation was then linked to protein kinase C by means of the protein kinase C inhibitor chelerythrine (20 mu mol . L(-1). 2 min(-1)). To determine whether ex ogenous calcium administration induces protein kinase C translocation and activation, immunohistochemical staining for the calcium-dependent protein kinase C isoform a was performed on adjacent 5 mu m myocardia l sections with and without calcium chloride treatment. Results indica ted that preischemic calcium chloride administration improved myocardi al functional recovery, as determined by enhanced developed pressure, improved coronary how, reduced end-diastolic pressure, and decreased c reatine kinase leakage during reperfusion, Beneficial effects of calci um chloride were eliminated by concurrent protein kinase C inhibition, Immunohistochemical staining for the a isoform of protein kinase C de monstrated that calcium chloride induces translocation of this isoform from the cytoplasm to the sarcolemma, indicating that exogenous calci um administration activates this isoform, These results suggest that c alcium chloride, a safe and routinely administered agent, can induce p rotein kinase C-mediated cardiac preconditioning. Calcium-induced card ioadaptation to ischemia-reperfusion injury may be promising as a clin ically feasible therapy before planned ischemic events such as cardiac allograft preservation and elective cardiac operations.