Effect of amrinone and milrinone on myocardial ischemia extent and infarct size in isolated rabbit hearts.
The effect of inotropics on myocardial ischemia is difficult to predict, since inotropics may influence the determinants of myocardial O2-demand and O2-supply differently. Several phosphodiesterase-inhibitors have been reported to possess antiischemic properties related in vivo to their hemodynamic and O2-sparing effects. The effects of amrinone (CAS 60719-84-8) (10(-6) mol/l or 5 x 10(-5) mol/l) or milrinone (CAS 78415-72-2) 10(-5) mol/l) on myocardial ischemia extent and infarct size were compared in isolated electrically paced rabbit hearts (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Myocardial ischemia was induced by left coronary artery branch occlusion and quantitated from epicardial NADH-fluorescence photography. Infarct size was determined by Evan's blue dye and nitroblue-tetrazolium staining and planimetry. At low concentration (10(-6) mol/l), amrinone had no significant influence on left ventricular pressure or coronary flow (p < 0.05) and epicardial NADH-fluorescence area or infarct size were not significantly affected compared to controls (p > 0.05). Amrinone (5 x 10(-5) mol/l) or milrinone (10(-5) mol/l) significantly increased left ventricular pressure (+10%, p < 0.05) and coronary flow (+30, 40%, p < 0.05) to a similar extent. Concomitantly, both agents similarly reduced epicardial NADH-fluorescence area (-25%, p < 0.05) and infarct size relative to the area at risk or ventricle size compared to controls (p < 0.05).


CONCLUSIONS
amrinone or milrinone possess comparable antiischemic effects in isolated rabbit hearts that seem to be related to coronary dilator activity of these agents.
Rump
A F
AF
Institut für Pharmakologie, Universität Köln, Fed. Rep. of Germany.
Blazincic
B
B
Klaus
W
W
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D005453:Fluorescence; D006439:Hemodynamics / Q000187:drug effects; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008297:Male; D020105:Milrinone; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits
D002316:Cardiotonic Agents; D011728:Pyridones; D009243:NAD; D020105:Milrinone; D000676:Amrinone