title: Beneficial effect of amrinone on the size of acute regional ischemia in isolated rabbit hearts.
abstract: The effect of inotropes on myocardial ischemia is difficult to predict because they may influence the determinants of myocardial O2 demand and O2 supply differently. Several PDE-inhibitors have been reported to possess antiischemic properties related to their hemodynamic and O2-sparing effects. To assess whether PDE-inhibitors also possess direct cardioprotective properties, the effects of amrinone (2.5 x 10(-5) mol/L) in comparison to isoproterenol (5 x 10(-9) mol/L) and ouabain (1.5 x 10(-7) mol/L) were studied in isolated rabbit hearts perfused according to Langendorff at a constant pressure (70 cmH2O) and electrically driven at a constant pacing rate. Regional ischemia was induced by coronary artery ligation and quantified by epicardial NADH fluorescence. All substances significantly increased the actively developed left ventricular pressure to a similar extent (+20%) (P < 0.05). Coronary flow was significantly decreased by ouabain (-15%) and significantly increased by isoproterenol (+25%) and particularly by amrinone (+50%) (P < 0.05). Neither ouabain nor isoproterenol significantly changed the intensity or the distribution pattern of NADH fluorescence, whereas the size of the ischemic zone was significantly reduced by amrinone (-25%) (P < 0.05). The PDE-inhibitor amrinone was shown to possess a direct cardioprotective effect by improving myocardial perfusion and O2 supply in isolated rabbit hearts.
authors.affiliation: Institut für Pharmakologie, Universität Köln, Germany.
authors.forename: A F
authors.initials: AF
authors.lastname: Rump
authors.forename: R
authors.initials: R
authors.lastname: Rösen
authors.forename: B
authors.initials: B
authors.lastname: Sigmund
authors.forename: J
authors.initials: J
authors.lastname: Fuchs
authors.forename: S
authors.initials: S
authors.lastname: Dhein
authors.forename: W
authors.initials: W
authors.lastname: Klaus
mesh_terms: D000676:Amrinone / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D005453:Fluorescence; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D010042:Ouabain / Q000627:therapeutic use; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D009243:NAD; D010042:Ouabain; D000676:Amrinone; D007545:Isoproterenol