Myocardial edema and cell swelling are common sequelae of cardiac surgery and have deleterious effects on postoperative cardiac physiology. Our principal hypothesis is that hyperkalemic cardioplegia itself, the most common method of myocardial protection, is responsible for this cell swelling. The objective of this proposal is to investigate the effect of cardioplegia on human myocyte volume regulation and contractility. Adult and neonatal human myocytes will be obtained during the course of routine cardiac surgery. Both atrial and ventricular myocytes will be isolated. Myocyte dimensions will be determined using high-resolution video microscopy coupled to a digital image analysis system. Each cell will serve as its own control. Experiments have been designed to test the hypothesis that standard hyperkalemic cardioplegia causes cell swelling. The mechanisms of cell swelling will be examined under both hypothermic and normothermic conditions. During hypothermia, our principle hypothesis is that the tonicity of the cardioplegia solution, that is the [K+]0X[Cl-]0 product of the cardioplegia, is the most important mechanism responsible for cell swelling. The role of the Na+/K+2Cl- co-transport system will be investigated under normothermic conditions. Moreover, comparisons will be drawn between adult and neonatal cells to identify differences in their cell volume regulation. We will than attempt to correlate changes in cell volume with cell contractility. Our goal is to delineate the mechanisms of cardioplegia-related cell swelling. Manipulation of cardioplegic solutions to prevent cell swelling may represent a new strategy to improve current techniques of myocardial protection.
