Mechanisms of substrate preference for oxidative metabolism during early myocardial reperfusion.
We previously reported in working swine hearts a preferred use of fatty acids during early myocardial reperfusion. The purpose of these studies was to test whether this pattern of substrate oxidation was the result of excess energy demands during mechanical recovery. Two groups of pig hearts (n = 15) were compared. Both received Intralipid with heparin (serum fatty acids, 1.02 +/- 0.05 mumol/ml) to ensure preferred substrate availability and both received [2-14C]pyruvate to monitor myocardial use of a carbohydrate substrate. In one group (n = 8) oxfenicine was administered to suppress fatty acid utilization. Left anterior descending (LAD) coronary flow was maintained at aerobic levels for 30 min, reduced by 60% for 45 min, and restored to aerobic levels for a final 50 min. Ischemia caused the expected decreased in global and regional mechanical performance. Recovery in motion during reflow was less in oxfenicine-treated hearts (73 vs. 32% decrease in systolic shortening from aerobic values in treated and control hearts, P less than or equal to 0.01 and P less than or equal to 0.05, respectively). Pyruvate oxidation declined dramatically in both groups during ischemia but recovered disparately. In control hearts CO2 production remained depressed during reperfusion (NS from ischemic values), whereas in treated hearts it increased 5.5-fold (but did not exceed aerobic values). Tissue levels of acetyl CoA and acetylcarnitine were not statistically different between perfusion beds (aerobic vs. reperfusion) within groups. Oxfenicine reduced levels of acetyl carnitine in both perfusion beds.(ABSTRACT TRUNCATED AT 250 WORDS)
Renstrom
B
B
Section of Cardiology, University of Wisconsin, Madison 53792.
Liedtke
A J
AJ
Nellis
S H
SH
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000108:Acetylcarnitine / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D005227:Fatty Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D013552:Swine
D005227:Fatty Acids; D011773:Pyruvates; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A; C023010:4-hydroxyphenylglycine; D019289:Pyruvic Acid; D005998:Glycine