High energy phosphates and catecholamine stores after prolonged ex vivo heart preservation

Previously, we have demonstrated that hearts preserved ex vivo for 12 hours maintain normal hemodynamic performance after orthotopic transplantation. To complete our studies of these preserved hearts, we evaluated myocardial metabolism by determining high energy phosphate levels and catecholamine concentrations in 22 canine hearts. Group I was the control group in which six hearts were given cold cardioplegic solution; full thickness biopsies were taken from the myocardium in two areas of the right and left ventricles and septum; and adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, creatine phosphate, and catecholamines were determined. Group II, in which the hearts were preserved 12 hours, had eight hearts that were stopped with cold cardioplegic solution, excised, and then preserved in an ex vivo state with a 32°C modified blood perfusate. After a 12-hour perfusion period, the hearts were stopped and biopsies taken. Group III involved cold ischemia and had six hearts stopped with cardioplegic solution, excised, opened, flushed, and stored for 2.5 hours at 2° to 4°C. Biopsies were obtained as in groups I and II. Adenosine triphosphate levels were slightly reduced in the 12 hour preserved heart when compared with the control group and the heart in the cold ischemia group preserved for 2.5 hours (p<0.01). Creatine phosphate levels were significantly elevated after 12 hour preservation when compared with groups I and III (p<0.01). Hearts preserved by cold ischemia also had a reduction (p=0.03) of creatine phosphate when compared with the control group. There were no significant differences in energy charge or in norepinephrine, epinephrine, or dopamine between groups. The data demonstrate that only a slight reduction of adenosine triphosphate levels occurs during the preservation period, and the levels are still well above those associated with moderate to severe dysfunction. Furthermore, mitochondrial function is adequately preserved as evidenced by both high creatine phosphate levels and normal energy charge values. Together with previously published reports of preservation of morphology and function, these data suggest that our technique offers an adequate and reproducible way to preserve and protect an organ before clinical heart transplantation.