Abstract 20879: Oxidative Substrate Increases Oxygen Consumption, Increases TCA Cycle Intermediates, and Reduces Lactate Production in the Machine Perfused Heart
Introduction: Oxygenated, hypothermic machine perfusion (HMP) has been shown to improve donor heart preservation. Effects on cardiac metabolism and substrate preferences under these conditions are unknown. Fatty acids, acetate, and ketones are preferred substrates of the heart but contributions to metabolism during HMP are not known.
Hypothesis: We assessed the hypothesis that these substrates increase myocardial metabolism, reduce lactate accumulation, and maintain tricarboxylic acid (TCA) cycle intermediates in perfused hearts.
Methods: Rat hearts (n=4/group) were perfused at 5°C for 6 hours with Carbon-13 (13C) labeled acetate (2, 4, 6, 8 mM), β-hydroxybutyrate (.25, .5, 1, 2 mM), or octanoate (1, 2, 4, 8 mM) containing University of Wisconsin Machine Perfusion Solution. Groups were compared to immediately freeze clamped and no substrate perfusion groups. TCA cycle intermediate concentrations were determined by GC/Mass Spectrometry. Exogenous substrate contributions to myocardial metabolism and TCA cycle intermediates were measured by 13C magnetic resonance spectroscopy. Myocardial oxygen consumption (MVO2) was determined from arteriovenous differences and coronary flow. Lactate accumulation was measured.
Results: MVO2 was increased and lactate levels were reduced in substrate containing groups. Acetate and octanoate were preferentially oxidized but β-hydroxybutyrate was a minor substrate. TCA cycle intermediates levels typically were higher in substrate containing perfusion groups compared to the no substrate perfusion group or the no ischemia control group. See Table.
Conclusions: In conclusion, the presence on an oxidizable substrate increases MVO2, reduces lactate accumulation, and increases TCA cycle intermediates during HMP. Acetate and octanoate are effective substrates for the cold perfused heart. The presence of an exogenous substrate appears important for maintaining oxidative metabolism over long intervals.
Author Disclosures: C. Holmes: None. L. Powell: None. M. Peltz: None. M.E. Jessen: None.
- © 2016 by American Heart Association, Inc.