title: Quantitative autoradiographic measurement of cocaine-induced regional myocardial metabolic changes in hypertensive rats.
abstract: A rat model of hypertensive cardiomyopathy was studied to evaluate the acute effects of cocaine on the myocardium. Using autoradiographic microimaging techniques, myocardial perfusion (201Tl) and energy substrate utilization (glucose: [14C]2-fluoro-2-deoxy-D-glucose-[14C]2DG and fatty acid (15-[p-iodophenyl])-3-R,S-methyl pentadecanoic acid-[131I]BMIPP) were studied in Dahl strain salt-sensitive normotensive and hypertensive rats with and without intravenous cocaine. The right ventricle, septum, endocardium and epicardium of the left ventricle were analyzed. Increased perfusion (18%) was seen in the myocardium of the hypertensive rats as compared to the normotensive rats. There was higher [14C]2DG (254%) and lower fatty acid (13.2%) uptake in the hypertensive rats, indicative of a shift from aerobic to anaerobic substrate utilization. In cocaine-treated normotensive rats, a generalized decrease in myocardial perfusion (30%) and increased glucose metabolism (89%) was seen. In cocaine-treated hypertensive rats, the increased myocardial perfusion (16%) was heterogeneous and was more pronounced in septum and epicardium. The endocardium and epicardium in the hypertensive rats showed an overall increase (23%) in glucose utilization after cocaine which was not as dramatic as was seen in the normotensive heart and a slight increase in fatty acid utilization. These results are consistent with prior observations that under pressure overload the myocardium responds non-uniformly. It may well be that the hypertensive cardiomyopathic heart is unable to respond to the challenge of cocaine by further increasing glucose utilization. These data obtained in an animal model of hypertension seem to indicate that hypertension may increase the risk of cardiac complications related to cocaine.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Som
authors.forename: Z H
authors.initials: ZH
authors.lastname: Oster
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: F F
authors.initials: FF
authors.lastname: Knapp
authors.forename: D F
authors.initials: DF
authors.lastname: Sacker
mesh_terms: D000818:Animals; D001345:Autoradiography; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D019966:Substance-Related Disorders / Q000378:metabolism
chemical_list: D009294:Narcotics; D017673:Sodium Chloride, Dietary; D003042:Cocaine