Postcardioplegia Acute Cardiac Dysfunction and Reperfusion Injury Jakob Vinten-Johansen, PhD, and Katsuhiko Nakanishi, MD In cardiac surgery, an obligatory period of ischemia is im- posed in order to provide a convenient operative field. Brief periods of ischemia produce systolic and diastolic abnormal- ities 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 dis- ease, hypotension, or ventricular fibrillation, between inter- mittent 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 reperfu- sion to previously ischemic myocardium. lschemic injury and repetfusion 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 dys- function, 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. How- ever, the cardioplegic solution itself may also contribute to postcardioplegic dysfunction by creating temporary ionic and metabolic abnormalities. In addition, systemic hypocalce- mia or hyperkalemia resulting from using large doses of T HE EXPEDITIOUS and successful conduct of cardiac surgery requires a quiescent heart and a bloodless field. Current techniques used to achieve this surgical environment include cardiopulmonary bypass, infusion of cardioplegia solutions with intervening periods of ischemia, and reperfusion of the previously ischemic myocardium after cross-clamp removal. These techniques provide obvi- ous benefits to the convenient performance of the opera- tion, but also adversely affect postoperative ventricular performance. For example, intermittent ischemia inter- posed between infusions of chemical cardioplegia solutions raises the potential for myocardial damage despite the modified conditions of delivery and additives designed to reduce or avoid the injury. Furthermore, this ischemic damage may be further exaggerated by activation of the complement cascade by the extracorporeal circuit, “ reoxy- genation injury” or “ reperfusion injury” after removal of the aortic cross-clamp, or premature or excessive adminis- tration of inotropic agents. It is paradoxical that the very techniques invoked to avoid intraoperative and postopera- From the Department of Cardiothoracic Surgery , The Bow man Gray School of Medicine, W inston-Salem, NC. Address reprint requests to Jakoh Vinten-Johansen, PhD, Depart- ment of Cardiothoracic Surge?), The Bow man Gray School of Medicine, Medical Center Blvd, W inston-Salem, NC 27157. Copyright o I993 by W . B. Saunders Company 1053- 0770/9310704- 0203$03.O O lO cardioplegic solution may temporarily aggravate postcardio- plegic 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 mechan- ical performance. lschemic injury is avoided by reducing myocardial oxygen demand by engaging immediate arrest and cooling the heart to approximately 10 degrees centi- grade, and intermittently infusing solution to reoxygenate the myocardium, maintain hypothermia, and wash out accu- mulated 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 micro- circulatory (endothelium) damage. Calcium accumulation during ischemia or reperfusion or both may be avoided by using hypocalcemic cardioplegic solutions. In addition, neu- trophils may be scavenged specifically from cardioplegic solutions, or inhibitors of neutrophil activation used to limit neutrophil-mediated injury. Therefore, the concept of cardio- plegic 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. Copyright t‘ 1993 by W. B. Saunders Company KEY WORDS: ventricular dysfunction, cardioplegia, myocar- dial stunning tive injury may themselves be contributory to these compli- cations. Postoperative ventricular dysfunction after cardiac sur- gery requiring cardioplegia is commonly encountered clini- ca11y’-5 and observed experimentally.h-x The frequency of its occurrence and the importance of both left ventricular and right ventricular function in successfully discontinuing by- pass makes postcardioplegia dysfunction a realistic prob- lem rather than a laboratory curiosity.” Postoperative myo- cardial dysfunction may be similar to myocardial “ stunning,” which is defined as postischemic systolic (and diastolic) dysfunction that is unassociated with morphologic injury (necrosis), and is reversible after a period of convalescence. After cardiac surgery, postischemic dysfunction may be relatively transient in preoperatively normal hearts2,3,s,i” but can be protracted in cases of severe preexisting left ventricular dysfunction. I ‘I Although originally observed in regionally ischemic myocardium after reversible coronary occlusion.” postsurgical “ stunning” after cardiac surgery encompasses both regional’3-‘h and global dysfunction since regional wall motion abnormalities may impact on global performancch,’ The phenomenon of postcardioplegia dys- function or “ stunning” may be observed in a wide spectrum of surgical conditions in which cardioplegic arrest and surgical ischemia have been imposed, including coronary artery bypass grafting (CABG),‘,4 valve repair, and trans- plantation. In contrast to regional stunning, which is largely unilateral, postsurgical stunning may involve both right and 6 Journalof CardvXhoracic and VascularAnesthesia, Vol7, No 4, Suppl 2 (August), 1993: pp 6-18 Sponsored by Sanofi Winthrop