Rump A F, Blazincic B, Klaus W
Institut für Pharmakologie, Universität Köln, Fed. Rep. of Germany.
Arzneimittelforschung. 1993 Dec;43(12):1262-6.
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).
amrinone or milrinone possess comparable antiischemic effects in isolated rabbit hearts that seem to be related to coronary dilator activity of these agents.
正性肌力药对心肌缺血的影响难以预测，因为正性肌力药可能会以不同方式影响心肌氧需求和氧供应的决定因素。据报道，几种磷酸二酯酶抑制剂具有抗缺血特性，在体内与其血流动力学和氧节省作用有关。在离体电刺激的兔心脏（Langendorff 装置，恒定压力：70 cm H₂O，台氏液，Ca²⁺ 1.8 mmol/L）中比较了氨力农（CAS 60719 - 84 - 8）（10⁻⁶ mol/L 或 5×10⁻⁵ mol/L）或米力农（CAS 78415 - 72 - 2）10⁻⁵ mol/L）对心肌缺血范围和梗死面积的影响。通过左冠状动脉分支闭塞诱导心肌缺血，并通过心外膜 NADH 荧光摄影进行定量。梗死面积通过伊文思蓝染料和硝基蓝四氮唑染色及平面测量法确定。在低浓度（10⁻⁶ mol/L）时，氨力农对左心室压力或冠状动脉流量无显著影响（p < 0.05），与对照组相比，心外膜 NADH 荧光面积或梗死面积未受到显著影响（p > 0.05）。氨力农（5×10⁻⁵ mol/L）或米力农（10⁻⁵ mol/L）使左心室压力显著增加（+10%，p < 0.05），冠状动脉流量显著增加（+30%、40%，p < 0.05），且增加程度相似。同时，与对照组相比，两种药物均使心外膜 NADH 荧光面积（-25%，p < 0.05）以及相对于危险区域或心室大小的梗死面积同样减少（p < 0.05）。
在离体兔心脏中，氨力农或米力农具有相当的抗缺血作用，这似乎与其冠状动脉扩张活性有关。
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