Effects of p-chlorophenoxyisobutyrate on myocardial free fatty acid extraction, ventricular blood flow, and epicardial ST-segment elevation during coronary occlusion in dogs.
The effect of p-chlorophenoxyisobutyrate (CPIB) on ST-segment elevation in epicardial electrocardiographic recordings was studied during coronary artery occlusion in dogs. Occlusion alone raised the sum of ST-segment elevations (sigmaST) to 26 +/- 6 mV (mean +/- SEM). Intravenous (i.v.) administration of CPIB 30 min before re-occlusion reduced sigmaST to 14 +/- 3 mV (P less than 0.03). A continuous i.v. infusion of isoproterenol increased sigmaST to 74 +/- 11 mV. Pretreatment with CPIB reduced sigmaST during isoproterenol infusion to 40 +/- 7 mV (P less than 0.005). CPIB had no effect on mean aortic blood pressure, heart rate, or regional myocardial blood flow, as measured by radioactive microspheres. Arterial free fatty acid (FFA) concentrations were reduced by CPIB from 466 +/- 41 to 221 +/- 44 muEq/L (P less than 0.001) in the basal state, and from 1966 +/- 183 to 1429 +/- 209 muEq/L (P less than 0.001) during isoproterenol infusion. The reduction in arterial FFA concentration was associated with a proportionate decrease in the myocardial extraction of FFA. Similar changes were observed when CPIB was administered during an occlusion which had been established 10 min earlier. These observations support other evidence that the severity of acute myocardial ischemic injury in dogs is positively correlated with the myocardial extraction of FFA, and that the severity of the ischemic injury can be reduced by effective antilipolytic therapy.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D002994:Clofibrate; D007545:Isoproterenol