Vleeming W, van der Wouw P A, van Rooij H H, Wemer J, Porsius A J
Faculty of Pharmacy, Department of Pharmacotherapy, University of Utrecht, the Netherlands.
J Pharmacol Methods. 1989 Apr;21(2):95-102. doi: 10.1016/0160-5402(89)90027-2.
In this paper, a method is described for the measurement of the performance of rat hearts with an experimentally induced myocardial infarction of the left ventricle. After ether anesthesia of the animals and left thoracotomy, the left coronary artery was ligated, and the thorax was rapidly closed. The whole procedure took no more than 2 min. Forty-eight hours after the operation, the hearts were prepared for retrograde constant pressure perfusion, according to the Langendorff technique. The effects of the betasympathomimetic drug dobutamine and of the novel phosphodiesterase inhibitor milrinone on the contractile force of the right ventricle and the infarcted left ventricle, as well as on the total coronary flow, were quantified. Sham operated animals were used as control. The maximal obtainable stimulation of the contractility of infarcted hearts by dobutamine was significantly reduced from control. Milrinone increased the contractility in control animals, although to a much lesser extent. This increase was significantly smaller in infarcted hearts. The stimulation of the coronary flow by dobutamine and milrinone was significantly reduced in hearts with an infarction. Milrinone potentiated the effect of isoprenaline significantly. The results of the present study indicate the usefulness and reproducibility of this model for the evaluation of the efficacy of positive inotropic agents on the heart in the presence of a myocardial infarction.
本文描述了一种测量实验性诱导左心室心肌梗死大鼠心脏功能的方法。对动物进行乙醚麻醉并开左胸后,结扎左冠状动脉,然后迅速关闭胸腔。整个过程不超过2分钟。术后48小时,根据Langendorff技术对心脏进行逆行恒压灌注。对β-拟交感神经药物多巴酚丁胺和新型磷酸二酯酶抑制剂米力农对右心室和梗死左心室收缩力以及总冠状动脉血流量的影响进行了量化。假手术动物用作对照。多巴酚丁胺对梗死心脏收缩力的最大可获得刺激作用比对照显著降低。米力农可增加对照动物的收缩力,尽管程度小得多。在梗死心脏中这种增加明显较小。多巴酚丁胺和米力农对梗死心脏冠状动脉血流量的刺激作用明显降低。米力农显著增强了异丙肾上腺素的作用。本研究结果表明该模型对于评估正性肌力药物在心肌梗死情况下对心脏的疗效具有实用性和可重复性。