Effects of acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) on cardiodynamics and myocardial metabolism in dogs.
An investigation is presented of the effects of the acylcarnitine-transferase blocking agent sodium 2[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA; 20 mg/kg i.v.) on cardiodynamics and myocardial metabolism in normoxic, anesthetized dogs. POCA induced an initial increase in pulmonary vascular resistance; pulmonary vascular pressure was increased up to 4 h. All other hemodynamic parameters were unchanged. POCA induced a continuous rise in arterial free fatty acid (FFA) level and a marked initial increase in arterial lactate level. Arterial glucose level decreased. Myocardial FFA uptake was almost completely inhibited by POCA; myocardial lactate uptake increased markedly and myocardial glucose uptake remained unchanged. These changes were accompanied by an increase in respiratory quotient from 0.72 to 1.0 and a decrease in myocardial oxygen consumption by 15-20%. In conscious dogs, POCA (20 mg/kg i.v.) induced similar changes in arterial substrate levels. The increase in arterial FFA level was accompanied by an increase in arterial glucagon. Ketone body levels decreased initially but increased simultaneously with glucagon levels. These findings confirm the efficacy of POCA in inhibiting FFA oxidation and, consequently, in decreasing myocardial oxygen consumption. However, possible deleterious effects of the increase in arterial FFA levels on the ischemic myocardium require further experimental evaluation.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D050260:Carbohydrate Metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D004285:Dogs; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D019344:Lactic Acid; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate; D005934:Glucagon; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D010100:Oxygen