The effects on myocardial damage of metabolic interventions by
nicotinic acid,
oxfenicine, or a combination of the two were assessed in open-chest dogs exposed to coronary artery occlusion for 6 hours. The accumulation of metabolites of
free fatty acids (FFAs) was studied in tissue samples of the left ventricle taken 60 minutes after
coronary occlusion in separate animals. The percentage of the hypoperfused zone that evolved to
infarction was 96 +/- 3% (mean +/- SEM) in control dogs, 74 +/- 4% in dogs treated with
nicotinic acid (p less than 0.05 vs control dogs), 72 +/- 2% in dogs treated with
oxfenicine (p less than 0.05 vs control dogs), and 54 +/- 5% in dogs with combined
nicotinic acid and
oxfenicine (p less than 0.05 vs control dogs, p less than 0.05 vs
nicotinic acid and
oxfenicine). Arterial FFA concentration was markedly reduced in dogs treated with
nicotinic acid and those treated with combination
nicotinic acid and
oxfenicine. The accumulation of long-chain acyl
carnitine was substantially reduced in the ischemic myocardium after
nicotinic acid,
oxfenicine, and a combination of the two, whereas the lowering of
long-chain acyl CoA was less pronounced. Thus,
nicotinic acid and
oxfenicine, which depress myocardial FFA metabolism by different mechanisms, both reduce
myocardial infarct size and their effects are additive.