Effects of Acylcarnitine-Transferase Blocking Agent Sodium 2[5-(4-Chlorophenyl)-Pentyl]-Oxirane-2-Carboxylate (POCA) on Cardiodynamics and Myocardial Metabolism in Dogs

Abstract

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 were studied. 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 O2 consumption by 15-20%. In conscious dogs, POCA (20 mg/kg i.v.) induced similar changes in arterial substrate levels. The arterial FFA level increase was accompanied by an arterial glucagon increase. Ketone body levels decreased initially but increased simultaneously with glucagon levels. These findings show the efficacy of POCA in inhibiting FFA oxidation and in decreasing myocardial O2 consumption. However, possible deleterious effects of the increase in arterial FFA levels on the ischemic myocardium require further experimention.