Postcardioplegia acute cardiac dysfunction and reperfusion injury

Abstract

In cardiac surgery, an obligatory period of ischemia is imposed in order to provide a convenient operative field. Brief periods of ischemia produce systolic and diastolic abnormalities related to pathology occurring during ischemia per se (ischemic injury) or expressed after the onset of reperfusion (reperfusion injury). In the surgical setting, ischemia may be encountered preoperatively with preexisting coronary disease, hypotension, or ventricular fibrillation, between intermittent infusions of cardioplegia solutions, or as a result of maldistribution of cardioplegia solution. The potential for reperfusion injury exists not only at the time of cross-clamp removal, but also with each infusion of cardioplegia solution. Infusion of cardioplegic solution is, in fact, a form of reperfusion to previously ischemic myocardium. Ischemic injury and reperfusion injury are intimately linked in that the severity of ischemia sets the stage for and determines, in part, the extent of reperfusion injury. Mild-to-moderate systolic dysfunction, which may be called “postcardioplegia stunning,” remains a significant complication after cardiac surgery. More significant postoperative functional depression may occur in hearts with severe preoperative dysfunction, and in operations requiring long cross-clamp times. In addition, the failure to adequately distribute cardioplegic solution to all areas of the myocardium because of coronary stenoses, high coronary resistance or inadequate delivery pressure-flow relations, contributes to postcardioplegia dysfunction. However, the cardioplegic solution itself may also contribute to postcard ioplegic dysfunction by creating temporary ionic and metabolic abnormalities. In addition, systemic hypocalcemia or hyperkalemia resulting from using large doses of cardioplegic solution may temporarily aggravate postcardioplegic mechanical dysfunction. Current formulations and strategies for delivery of cardioplegia solutions are designed to address the various contributors to both ischemic and reperfusion injury that may impact on postoperative mechanical performance. Ischemic injury is avoided by reducing myocardial oxygen demand by engaging immediate arrest and cooling the heart to approximately 10 degrees centigrade, and intermittently infusing solution to reoxygenate the myocardium, maintain hypothermia, and wash out accumulated metabolites. Reperfusion injury may be avoided by infusing hyperosmotic solutions at moderate pressures, and by incorporating oxygen radical scavengers or inhibitors to reduce membrane lipid peroxidation, myocellular and microcirculatory (endothelium) damage. Calcium accumulation during ischemia or reperfusion or both may be avoided by using hypocalcemic cardioplegic solutions. In addition, neutrophils may be scavenged specifically from cardioplegic solutions, or inhibitors of neutrophil activation used to limit neutrophil-mediated injury. Therefore, the concept of cardioplegic solutions has expanded from its original use as a method of inducing mechanical quiescence, to a vehicle for delivery of target-specific pharmacologic agents aimed at the multiplicity of factors contributing to ischemic-reperfusion injury. The use of cardioplegic solutions has contributed greatly to avoiding postcardioplegic dysfunction.