Abstract
The effects of β-oxidation on the contractile recovery and metabolic activity of postischemic (10 min) rabbit hearts were examined during reperfusion with the short-chain fatty acid butyrate. Hearts received either 13C-enriched butyrate or acetate to evaluate metabolic targeting with 13C nuclear magnetic resonance (NMR) spectroscopy. Acetate and butyrate supported similar contractility (rate of pressure development, dP/dt) and 31P-NMR-detected, high-energy phosphate (HEP) levels during normal perfusion. In postischemic hearts, butyrate sustained a greater percentage of preischemic dP/dt (83 ± 4%) than did acetate reperfusion (44 ± 6%, P < 0.05) with no differences in HEP. The efficiency of oxygen consumption per unit of work was greater in hearts reperfused with butyrate (2.8 ± 0.2 μM·g-1·mmHg-1) vs. acetate (3.4 ± 0.1). Inhibition of butyrate oxidation with 4-bromocrotonic acid (4-BCA) during normal perfusion severely reduced dP/dt and HEP. Acetate supported normal dP/dt and HEP levels during perfusion with 4-BCA and butyrate, but contractile recovery during reperfusion with acetate, 4-BCA, and butyrate (46 ± 6%) was similar to that with acetate alone. With acetate and butyrate combined at reperfusion, acetate accounted for 56% of substrate entering oxidative metabolism at acetyl CoA and delayed contractile recovery (57 ± 5% at midpoint and 80 ± 6% at end). Thus improved respiratory efficiency of contraction in reperfused hearts was related to the activity of β-oxidation.