Ischemia-Reperfusion Injury

Abstract

While reperfusion injury is widely considered to represent a component of the infarction process related to epicardial growth and normalization of antegrade blood flow, the term ischemia/reperfusion (I/R) injury is frequently used synonymously with the "no reflow" phenomenon. I/R injury after cardiac surgery is completely different from I/R injury after spontaneous myocardial infarction (MI). During reperfusion, ion transfer is rapidly altered and cytotoxicity develops as pH is normalized. Na+ dependent pH regulation mechanisms such as, Na+ - H+ and Na+ - HCO3+ transport are activated, triggering the accumulation of intracellular Na+. Elevated intracellular Na+ levels are associated with increased intracellular Ca+2 concentrations through the activity of the Na+ - Ca+2 exchanger. Elevated Ca+2 ion concentrations have a cytotoxic impact. After completion of the surgical procedure, when the cross clamp is released, the cardiac tissues are re-perfused with a highly anticoagulated and oxygenated blood, which is affected from the immunological effects of the cardiopulmonary bypass pump. Thus, after cardiac surgery myocardium is exposed to excessive ischemia and reperfusion injury that may manifest themselves as arrhythmias, myocardial stunning, low cardiac output or postoperative MI. The cornerstone of the myocardial protection during cardiac surgery is the use of cardioplegic solutions containing potassium, mannitol and glucose. The metabolic requirements are minimized by myocardial arrest. Although the composition of cardioplegic solutions evolves with accumulating experience, I/R injury still occurs after cardioplegia.