title: Effect of ibopamine on ventricular remodeling after experimental myocardial infarction: a comparison with captopril.
abstract: Remodeling after myocardial infarction (MI) is influenced not only by hemodynamic but possibly by neurohumoral factors as well. Ibopamine is an orally active dopamine agonist (DA) with both hemodynamic and neurohumoral properties in humans. The latter property prevails in rats. To study the dose-dependent effect of ibopamine on myocardial remodeling and compare it with the effect of captopril, we randomized rats with (n = 27) or without (n = 27) experimental MI to captopril (25 mg/kg/day), low-dose ibopamine (10 mg/kg/day), high-dose ibopamine (30 mg/kg/day), or no treatment. After 8-week treatment, hearts were isolated and left ventricular (LV) function, LV cavity volume, and infarct size (IS) were evaluated. Both ibopamine and captopril significantly reduced plasma norepinephrine (NE) levels in rats with MI. In untreated but not in treated infarcted rats, LV function was significantly reduced as compared with that of controls. IS was reduced in all three active treatment groups as compared with untreated rats. LV cavity volume was significantly increased in untreated rats with MI as compared with controls. This dilatation was attenuated by both ibopamine and captopril. Ibopamine, comparable to captopril, administered early after coronary ligation reduced IS and subsequent ventricular dilatation, resulting in preservation of cardiac function in this rat model. This observation suggests a major role for neurohumoral activation in the process of remodeling.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: van Gilst
authors.forename: D J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: H
authors.initials: H
authors.lastname: Hegeman
authors.forename: H
authors.initials: H
authors.lastname: Buikema
authors.forename: E
authors.initials: E
authors.lastname: Scholtens
authors.forename: P A
authors.initials: PA
authors.lastname: de Graeff
authors.forename: K I
authors.initials: KI
authors.lastname: Lie
mesh_terms: D000818:Animals; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002395:Catecholamines / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002395:Catecholamines; C023487:ibopamine; D002216:Captopril; D003846:Deoxyepinephrine