Myocardial functional decline during prolonged ex situ heart perfusion

Abstract Background Myocardial function declines in a time dependent fashion during ex situ heart perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe perfusion period and the potential of ex situ heart perfusion to expand the donor pool. Our aim is to investigate the etiology of myocardial functional decline in ex situ perfused hearts. Methods Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig hearts, perfused for 12 hours. These hearts were perfused either in non-working mode (NWM), or working mode (WM). Results Cardiac function declined during ex situ heart perfusion regardless of perfusion mode but was significantly better preserved in the hearts perfused in WM (11-hour cardiac index / 1-hour cardiac index: WM=33 vs. NWM=10%, p=0.025). The rate of apoptosis was higher in the ex situ perfused hearts compared to in vivo samples (% apoptotic cells: in vivo =0.13, WM=0.54, NWM=0.88%, p Conclusions Hearts preserved ex situ experience a significant decline in myocardial function over time that is out of proportion to the magnitude of myocyte cell death present in dysfunctional hearts. Alterations in myocardial substrate utilization during prolonged ex situ heart perfusion may contribute to this phenomenon, and represent an avenue to improve donor heart preservation.