Liu X K, Engelman R M, Agrawal H R, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06010.
J Mol Cell Cardiol. 1991 Oct;23(10):1091-100. doi: 10.1016/0022-2828(91)90199-v.
In this study, we examined the effects of three different beta-blockers, propranolol, pindolol, and metoprolol, on membrane phospholipid preservation in the ischemic and reperfused rat heart. Isolated rat hearts were perfused with Krebs-Henseleit bicarbonate buffer by the Langdendorff technique in the presence or absence of propranolol, pindolol, or metroprolol (20 microM each) for 15 mins at 37 degrees C. Hearts where then either made ischemic alone at 37 degrees C for 30 mins, or followed by 30 mins of reperfusion. Coronary flow and perfusate creatine kinase content were monitored during both pre- and post-ischemic periods. At the end of the experiment, hearts were frozen by freeze-clamping at liquid nitrogen temperature. Membrane phospholipids, fatty acid composition of these phospholipids, non-esterified free fatty acids, and myocardial thiobabituric acid (TBA) reactive product were examined in these hearts. The beta-blocker-treated hearts exhibited significantly less lipid peroxidation than the control hearts (P less than 0.05), as indicated by decreased formation of TBA reactive product and the higher percentage of unsaturated fatty acids in the phosphatidylcholine (PC) in heart. In addition, compared to the control group, less accumulation of free fatty acids was observed in the propranolol and pindolol treated groups. Finally, reduced myocardial creatine kinase release and enhanced recovery of coronary flow indicated significant myocardial preservation by these beta-blockers. The efficacy of these beta-blockers were in the following order: propranolol, pindolol, metoprolol. These results suggest that beta-blockers could also protect an ischemic heart from reperfusion injury by preserving the membrane phospholipids.
在本研究中，我们检测了三种不同的β受体阻滞剂——普萘洛尔、吲哚洛尔和美托洛尔对缺血再灌注大鼠心脏膜磷脂保存的影响。采用Langendorff技术，在37℃下，用Krebs-Henseleit碳酸氢盐缓冲液灌注离体大鼠心脏，灌注液中分别添加或不添加普萘洛尔、吲哚洛尔或美托洛尔（各20μM），持续15分钟。然后，心脏在37℃下单独缺血30分钟，或缺血30分钟后再灌注30分钟。在缺血前后监测冠状动脉血流量和灌注液中肌酸激酶含量。实验结束时，将心脏在液氮温度下通过冷冻钳夹进行冷冻。检测这些心脏中的膜磷脂、这些磷脂的脂肪酸组成、非酯化游离脂肪酸和心肌硫代巴比妥酸（TBA）反应产物。β受体阻滞剂处理的心脏脂质过氧化明显低于对照组心脏（P<0.05），这表现为TBA反应产物形成减少以及心脏中磷脂酰胆碱（PC）中不饱和脂肪酸的百分比更高。此外，与对照组相比，普萘洛尔和吲哚洛尔处理组中游离脂肪酸的积累较少。最后，心肌肌酸激酶释放减少以及冠状动脉血流量恢复增强表明这些β受体阻滞剂对心肌有显著的保护作用。这些β受体阻滞剂的疗效顺序如下：普萘洛尔、吲哚洛尔、美托洛尔。这些结果表明，β受体阻滞剂还可以通过保存膜磷脂来保护缺血心脏免受再灌注损伤。
