Limitation of myocardial infarct size by metabolic interventions that reduce accumulation of fatty acid metabolites in ischemic myocardium.
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.
D000108:Acetylcarnitine / Q000032:analysis; D000214:Acyl Coenzyme A / Q000032:analysis; D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D004285:Dogs; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007773:Lactates / Q000032:analysis; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000032:analysis; D009525:Niacin / Q000008:administration & dosage / Q000627:therapeutic use*
D000214:Acyl Coenzyme A; D000227:Adenine Nucleotides; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D009525:Niacin; D000108:Acetylcarnitine; C023010:4-hydroxyphenylglycine; D005998:Glycine