Myocardial protection for transplantation

Abstract

PROGRESS in the development of new techniques in surgery of heart transplantation had considerable influence on the creation of new methods for heart preservation. Currently, various cardioplegic solutions, developed for cardiac surgery, provide safe preservation of myocardial function for 5 to 6 hours, but remain unsatisfactory. The process of clinical heart preservation usually begins with identification of the brain death of the donor. Effective preservation allows time for confirmatory tests of brain death, organization of cooperating teams for organ removal, HLA-typing and crossmatching of donor tissues against a pool of waiting recipients, excluding associated transplantable disease such as infection or neoplasm of the donor, selecting and locating recipients, and arranging recipient operating teams and time to transport organs over long distances. In the course of cardiac transplantation, donor hearts undergo a four-step sequence of events (cardiac arrest, cold storage, global ischemia during implantation, and reperfusion) during which time myocardial damage can occur. Simple cooling markedly enhances ischemic tolerance, diminishes metabolic activity, curtails oxygen demand, and slows degradation of energy stores. Transmembrane passive diffusion of ions is not appreciably affected by hypothermia, while active transport mechanisms, such as those governed by Na1/K1 ATP-ase and Mg21/Ca21 ATP-ase are inhibited below 10° C. Therefore, a major requirement for a cold flushing solution is an impermeant-providing osmotic force to oppose cellular oedema. High molecular weight anions (lactobionate) or nonelectrolytes (saccharoids, raffinose, sucrose) or chelates of citrate and magnesium can achieve this. An effective buffer (phosphate, citrate, histidine) counters cellular acidosis. The presence of glutathione in cardioplegic solution prevents oxygen-derived free radical injury, whereas the presence of glutamate prevents concracture by enhancement of energy production. The present study is a randomized clinical trial assessing preservation of the donor heart using three common cardioplegic solutions (Table 1). The Belzer solution developed at the University of Wisconsin (UW) contains a high concentration of K1 2125 mmol/L, which causes depolarization of the myocytes, enzyme dysfunction, decreases membrane stability, and Ca11 sequestration. The original Bretschneider solution (HTK) causes nondepolarizing cardiac arrest due to the presence of histidine. The Celsior cardioplegic solution offers the possibility of being used not only as a storage medium, but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation, and early reperfusion.