Modern techniques of myocardial preservation during cardiac surgery involve the use of hyperkalemic cardioplegia which induces depolarized arrest. Morbidity and mortality following cardiac operations has decreased significantly with the advent of these solutions. Although effective, there remain inherent drawbacks associated with potassium cardioplegia which result in a significant incidence of postoperative cardiac arrhythmias and conduction abnormalities. The goal of this research project is to study an alternative, more physiologic form of cardioplegia based on the mechanism of hyperpolarized arrest. It is our hypothesis that hyperpolarizing the myocyte to achieve arrest at an electrochemical potential that resembles the myocyte at rest will eliminate the compensatory metabolic processes and abnormal transmembrane ionic gradients observed at depolarized membrane potentials. Hyperpolarized arrest will be studied in the isolated heart model and in the intact porcine model, using functional, electrophysiologic, and histologic criteria. Hyperpolarized arrest will be induced by potassium channel openers (PCOs). PCOs are a class of compounds which open ATP- sensitive potassium channels in the heart. These channels have been shown to have a natural cardioprotective effect by opening to hyperpolarize the membrane and shorten the action potential in times of ATP depletion. The use of PCOs, therefore, may avoid significant reperfusion injury and replace potassium cardioplegia in the induction of elective cardiac arrest.
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