PRESERVATION OF MEMBRANE PHOSPHOLIPIDS BY PROPRANOLOL, PINDOLOL, AND METOPROLOL - A NOVEL MECHANISM OF ACTION OF BETA-BLOCKERS

In this study, we examined the effects of three different β-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 μm each) for 15 mins at 37°C. Hearts where then either made ischemic alone at 37°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 β-blocker-treated hearts exhibited significantly less lipid peroxidation than the control hearts (P < 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 β-blockers. The efficacy of these β-blockers were in the following order: propranolol, pindolol, metoprolol. These results suggest that β-blockers could also protect an ischemic heart from reperfusion injury by preserving the membrane phospholipids. © 1991.