Metabolic Alterations in Myocardial Metabolism during Ex Situ Heart Perfusion

Abstract

Purpose Ex situ heart perfusion (ESHP) is a novel method for preservation of the donated heart in a semi-physiologic state and provides the opportunity to evaluate pre-transplant function. Because of the well-described extraordinary metabolic requirements of the heart, efficient metabolic support is critical for optimal preservation of function and viability. Our aim was to determine changes in energy metabolism/energy substrates during extended ex situ perfusion of hearts in two different perfusion modes, working mode (WM) and non-working mode (NWM). Methods 17 female domestic breed pigs (37-47 kg) were included. Hearts were perfused on a custom ESHP apparatus (12 hours, NWM n=6 and WM n=7) with insulin and glucose infusions for metabolic support. Cardiac function, and changes in myocardial oxidative metabolism, glucose utilization, lactate, free fatty acids (FFA) and triglycerides (TG) were evaluated during ESHP. The enzymatic activity of pyruvate kinase was assessed using immunoassay techniques. The results were compared with baseline values (in vivo, n=4). Results Cardiac function declined over time but it was better preserved in WM (cardiac index change, p=0.02). Glucose utilization increased overtime in both groups (WM p=0.04, NWM p=0.04). Venous and arteriovenous lactate did not change over time and were not different between WM and NWM. FFA concentrations declined considerably during ESHP in both groups (WM p Conclusion Our data suggests functional decline during ESHP has a metabolic basis and is therefore reversible. Furthermore, a strategy of insulin and glucose appears insufficient for maintenance of metabolic integrity during ESHP and there is decoupling of glycolysis and the TCA cycle at the level of pyruvate kinase. Further research is required to determine the causative factors underpinning these alterations and optimal methods to abrogate their effects to ensure optimal preservation of contractile function during ESHP.