CARDIAC SURGICAL IMPLICATIONS OF CALCIUM DYSHOMEOSTASIS IN THE HEART

The prevalence of coronary artery disease renders myocardial ischemia a leading cause of morbidity and mortality. Both cardiac bypass operat ions and cardiac transplantation cause myocardial ischemia and reperfu sion injury. Intracellular calcium transport and regulation are of par amount importance in both normal and pathologic myocardial states. Cal cium regulation is integral to nearly every myocyte function, from ear ly development to senescence, Normal intracellular calcium-mediated ex citation-contraction coupling and abnormal patterns of calcium regulat ion leading to systolic/diastolic dysfunction are now therapeutically accessible to the cardiac surgeon. Additionally, altered Ca2+ transpor t protein gene expression is a mechanism of myocardial dysfunction. Th erapeutic strategies involve receptor-mediated transduction of signals to intracellular metabolic sites. Evidence implicates protein kinase C as well as a potential therapeutic role for Ca2+. The potential for pharmacologic access to this protective state has abundant clinical ap peal. The protective state (cardiac ''preconditioning'') is transient but is amenable as therapy against operation-related ischemic events.