Beneficial effect of amrinone on the size of acute regional ischemia in isolated rabbit hearts.
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.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Germany.
Rösen
R
R
Sigmund
B
B
Fuchs
J
J
Dhein
S
S
Klaus
W
W
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
D009243:NAD; D010042:Ouabain; D000676:Amrinone; D007545:Isoproterenol