NMR studies of beta-oxidation and short-chain fatty acid metabolism during recovery of reperfused hearts.
The effects of beta-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 less than 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 microM.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 beta-oxidation.
Lewandowski
E D
ED
Department of Medicine, Baylor College of Medicine, Houston 77030.
Chari
M V
MV
Roberts
R
R
Johnston
D L
DL
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002087:Butyrates / Q000037:antagonists & inhibitors / Q000378:metabolism; D020148:Butyric Acid; D003437:Crotonates / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011817:Rabbits
D000085:Acetates; D002087:Butyrates; D003437:Crotonates; D005227:Fatty Acids; D020148:Butyric Acid; C034444:4-bromocrotonic acid