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 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.
Department of Surgery, University of Connecticut School of Medicine, Farmington 06010.
X K
XK
Liu
R M
RM
Engelman
H R
HR
Agrawal
D K
DK
Das
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008790:Metoprolol / Q000494:pharmacology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D010869:Pindolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000517:prevention & control*
D000319:Adrenergic beta-Antagonists; D005227:Fatty Acids; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010743:Phospholipids; D011433:Propranolol; D010869:Pindolol; D003402:Creatine Kinase; D008790:Metoprolol