Changes in the preserved heart that limit the length of preservation

The variability in donor heart viability following preservation is well known and very dependent on the animal model used and the methods of preservation. Using hypothermia (2 to 4 degrees C) with the University of Wisconsin solution and microperfusion (3 microl/g/min) myocardial functional recovery after reperfusion is 50% to 60% after 18 hours of preservation. Many investigators have found the 18-hour preservation barrier for functional recovery of the heart with different experimental protocols. In previous studies, we have found in normothermic global ischemia that with necrosis there was a significant amount of apoptosis. It was therefore the purpose of this study to investigate the importance of apoptosis in heart preservation and determine if this cellular disruption plays a part in limiting heart viability during recovery from preservation.

Using a heterotopic heart transplant model, myocardial function (end-systolic elastance), high energy phosphate changes, metabolic substrate utilization, electron microscopy to determine degree of injury, and histologic changes that included apoptosis and lamin B(1) analyses were conducted on canine hearts preserved for 18 hours and reperfused for 6 hours. The changes were compared with a control group with no preservation.

The 18-hour preserved heart regained approximately 50% to 60% of its original function, with significant decreases in adenosine triphosphate, no irreversible cellular changes (necrosis), and a 6% to 8% increase in apoptotic myocytes with a concomitant 8% decrease in lamin B(1).

Preserved hearts can be maintained for approximately 12 hours with functional recovery near normal. However, approaching 18 hours, there is an attenuated functional response which may be related to the to development of apoptosis.