CARD28: Prolonged Graft Preservation of Biostasis Induced Porcine Hearts using the VP.S ENCORE® Machine Perfusion Device

Abstract

Purpose: Heart transplantation is the gold standard therapy for patients with end-stage heart failure. However, the supply of donor hearts does not meet the demand, and many patients die on the waitlist. The purpose of this study was to test the efficacy of a novel machine perfusion device, the VP.S ENCORE® cardiac preservation device, in preserving porcine hearts conditioned with a biostasis-inducing compound (WC1) during prolonged 6-8 hour perfusion. Methods: Isolated porcine hearts were recovered under anesthesia. Following cannulation, the hearts were placed in the VP.S ENCORE® cardiac preservation device for oxygenated perfusion at 23-25°C for either 6 (n = 3) or 8 (n = 4) hours. At hour 3, WC1 (n = 2) was administered through the arterial line and the hearts continued to be perfused for additional 5 hours. Hourly flow, pressure, temperature, blood gases, and various metabolites were recorded. After preservation, hearts were placed in a Langendorff model for reperfusion and evaluated for cardiac function. Biopsy samples were taken before and at the end of preservation for histological and gene expression analyses. Results: During perfusion, oxygen consumption was significantly reduced in WC1-treated hearts (p < 0.0001). However, during re-perfusion, WC1-treated hearts had an initial lower oxygen consumption that recovered to normal with time and temperature. Before defibrillating the hearts, oxygen consumption was 1.61 ± 0.59 (vehicle) & 1.05 ± 0.39 (WC1), while after defibrillation the oxygen consumption increased to 3.29 ± 0.63 & 2.66 ± 0.32 ml/min/100g, respectively. The contractility of the WC1-treated hearts was similar to a normal human heart in vivo. Furthermore, gene expression analysis showed a significant reduction (p < 0.0008) of inflammation (IL-6, TNFα), hypoxia (Hif1a), & cell death markers (p53) in WC1 treated hearts when compared to control hearts. Conclusions: Our preliminary results demonstrate that the portable, simple-to-use VP.S ENCORE® cardiac preservation machine perfusion device coupled with the torpor properties of compounds like WC1 may provide a new paradigm to prolonged organ preservation, and may offer many advantages over currently tested machine perfusion technologies. Further, this innovative work is a result of integrating science and engineering to target unmet patients’ needs in the field of organ preservation.Figure 1. Subnormothermic Perfusion of Porcine Hearts using VP.S ENCORE®