P153: Metabolic benefits of perfusion preservation in canine hearts stored for short intervals

Abstract

Background: Current methods of preservation for heart transplantation limit safe storage intervals to approximately 6 hours. Recently, investigators have tested continuous perfusion devices in an attempt to improve ischemic tolerance and extend the duration of preservation. However, initial clinical trials of continuous preservation techniques in humans are likely to involve standard preservation time intervals, and few studies have examined the functional and metabolic sequelae of these strategies over short ischemic intervals. As well, the effects of continuous perfusion on cellular metabolism and myocardial edema development are not well-defined. This study was designed to test a continuous perfusion strategy for cardiac preservation in a large animal model over a clinically relevant storage interval. Methods: Hearts from adult mongrel dogs were instrumented with sonomicrometry crystals and a left ventricular (LV) micromanometer-tipped catheter. A range of filling conditions was created by vena caval occlusion and LV function was quantified by the preload-recruitable stroke work (PRSW) relationship. Hearts were arrested with Celsior solution supplemented with 5 mM glucose, removed, and randomized to storage in this modified Celsior solution in an ice chest (n=6) or placement in a device (LifeCradle, Organ Transport Systems) providing continuous perfusion of the identical solution at 10ml/100g/min (n=4). All hearts were stored for 4 hours. At end-storage, samples of left atrium were frozen and later extracted and analyzed by magnetic resonance spectroscopy (MRS). Hearts were then transplanted into recipient dogs, separated from cardiopulmonary bypass, and reperfused for 6 hours, with function measured hourly. At end-experiment, LV tissue water content was determined, and serum CK-MB levels were measured. Results: LV function was similar at baseline in both the perfused and statically stored organs (PRSW: 48.3 ± 6.3 vs 51.0 ± 1.9 mmHg, mean ± SEM, respectively; p=0.86). As expected, LV functional recovery was excellent in both groups after 6 hours of reperfusion (46.1 ± 6.8 vs 39.6 ± 10.8 mmHg; p=0.66), although there appeared to be a slight trend towards improved function in the continuously perfused hearts over the entire 6 hour reperfusion interval (p=0.13, repeated measures ANOVA). Serum CK-MB levels after 6 hours of reperfusion were similar (11.2 ± 6.1 vs 10.2 ± 3.9 ng/ml, p=0.89) in the perfused and statically preserved organs respectively. Despite continuous perfusion during storage, LV water content was not increased in the perfusion preservation group when compared to routine storage (78.8 ± 0.3% vs 78.3 ± 0.2%; p=0.24.). However, MRS of tissue collected at the end of the storage interval revealed significantly elevated tissue lactate levels in the routinely stored organs (expressed as lactate to alanine ratio; 0.6 ± 0.4 vs 4.0 ± 0.5; p<0.01). Conclusions: Both methods of preservation lead to good early graft function after 4 hours of protected ischemia. However, continuous perfusion of donor hearts stored for transplantation nearly eliminates tissue lactate accumulation without increasing myocardial edema. This finding may imply maintenance of oxidative metabolism and/or washout of products of anaerobic metabolism during storage. A strategy of perfusion preservation appears promising for improving donor heart preservation even over relatively short periods of cold ischemia.