Myocardial and pulmonary protection: Long-distance transport

Abstract

MYOCARDIAL PROTECTION Experimental Laboratory Experience E ARLY INTEREST IN cardiac transplantation sparked intense investigation into myocardial protection. The primary method of protection in the 60s and early 70s was either fibrillatory arrest or direct coronary ostial perfusion.~ Complete cardiectomy for transplantation required the application of innovative techniques to preserve the heart during the obligate period of ischemia. Previous experience had documented the efficacy of hypothermia as an effective method for preservation of heart structure. 2'4 Transplantation efforts resulted in the concept of topical cooling, which was applied clinically to routine heart operations and remains today the cornerstone for cardiac preservation, usually in conjunction with some type of cardioplegia solution. Two major schools of interest have evolved in the technique of heart preservation for transplantation: static and pulsatile/nonpulsatile perfusion preservation. The use of topical hypothermia alone for cardiac preservation has been repeatedly shown to be effective for short periods of preservation. 5'6 The addition of a cardioplegic solution in combination with hypothermia provided adequate protection following 24 hours of preservation, initially demonstrated in 1974. 7 Numerous other investigators in recent years have shown the effectiveness of simple hypothermic storage for preservation. 81~ Perfusion preservation of the heart for transplantation was reported in 1973 when Copeland and coinvestigators demonstrated the efficacy of this type of preservation technique following 24 to 28 hours of ischemia. 11 The index of effectiveness was survival of the animal following orthotopic transplantation. These results suggested that low perfusion pressure (18 to 19 cm HzO ) resulted in improved survival. Recent reports by Wicomb and coinvestigators show successful orthotopic transplantation of baboon hearts preserved for 20 to 24 hours using a portable apparatus for storage and perfusion. ~215 These experiments resulted in the application of this technique to patients undergoing heterotopic heart transplantation. ~6 Although all of these techniques have resulted in adequate preservation of the heart for varying periods of time, no successful clinical technique of prolonged preservation has evolved from these studies. Inconsistency of results has marked most studies resulting in the current technique of static preservation for less than 5 hours, a technique not dissimilar to what was originally described two decades ago. 5'6 More recently, an attempt has been made to design a solution capable of preserving donor organs using the basic principles of anaerobic hypothermic ischemia or organ-specific metabolism. ~7 Application of this perfusate, however, has been primarily with livers, kidneys, and pancreas. The current thrust of investigation into organ preservation has been in the field of oxygen free radical scavengers. Increasing experimental evidence suggests that the major determinant of myocardial injury following preservation occurs during reperfusion at which time there is a generation of oxygen free radicals and their metabolites (superoxide, anion [O2], hydrogen peroxide [H202], and hydroxyl-radical [OH]). 1821 McCord and Roy showed that generation of free radicals occurred during reoxygenation via the hypoxanthine-xanthine oxidase reaction. 22 Oxygen is primarily reduced to water by the cytochrome oxidase system. Although the majority of oxygen undergoes this type of degradation, a small amount is reduced univalently resulting in the formation of these reactive oxygen intermediates or oxygen free radicals. Under stable conditions, naturally occurring enzymes (oxygen free radical scavengers) eliminate these free radical species. However, during ischemia these endogenous catalytic agents are diminished. Following a period of prolonged ischemia and subsequent reperfusion, oxygen free radical generation is substantially increased, which overwhelms the