Abstract
The effect of inotropes on myocardial ischemia is difficult to predict because they may influence the determinants of myocardial O 2 demand and O 2 supply differently. Several PDE-inhibitors have been reported to possess antiischemic properties related to their hemodynamic and 02-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 cmH 2O) 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 O 2 supply in isolated rabbit hearts.
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