Differences in Metabolic Profiles of Human Hearts after 6 Hour Preservation with a Novel Hypothermic Machine Perfusion Preservation Device Compared to Cold Storage

Summary of Objectives

While cardiac transplantation remains the most effective therapy for end-stage heart failure, it continues to be plagued by a severe donor shortage. Many potentially suitable organs are not transplanted due to concerns of inadequate preservation with hypothermic static storage. Experimental and clinical studies suggest that machine perfusion preservation improves myocardial preservation. The purpose of this study is to test the hypothesis that a novel hypothermic machine perfusion preservation device maintains allograft oxidative metabolism, limits lactate accumulation, and more effectively preserves high energy phosphate stores compared to cold storage in a human model.

Methods

Human donor hearts rejected or not offered for transplantation are eligible for this study through an organ procurement organization approved research protocol. Offered organs will be assigned to 6 hours of preservation either by conventional hypothermic static storage or hypothermic machine perfusion with a novel device by Paragonix Technologies, Inc. Donor demographic and diagnostic data will be collected. Myocardial oxygen consumption, lactate accumulation, temperature regulation and coronary flow will be measured in perfused hearts. After completion of the storage interval, myocardial biopsies will be obtained for proton and phosphorus-31 magnetic resonance spectroscopy, gas chromatography/mass spectroscopy and histologic studies. TCA cycle intermediates, high energy phosphates (ATP, phosphocreatine), lactate/alanine ratios will be measured. Cell death will be quantified by TUNEL. Groups will be compared by the Student's t-test or ANOVA as appropriate. A p-value < 0.05 will be considered significant.

Endpoints

We expect to show that the machine perfusion device maintains an oxidative metabolic profile and low lactate levels. We anticipate machine perfusion preservation better preserves citric acid cycle intermediates, reduces cell death and increases high energy phosphate levels compared to static storage.