Effect of the combination of glibenclamide, an ATP-dependent potassium channel blocker, and metoprolol, a cardioselective $beta$-adrenoceptor blocker, during myocardial infarction in conscious rats
Effect of the combination of glibenclamide, an ATP-dependent potassium channel blocker, and metoprolol, a cardioselective $beta$-adrenoceptor blocker, during myocardial infarction in conscious rats
We investigated the possible interaction of glibenclamide and metoprolol on the occurrence of life threatening arrhythmias during the acute phase of experimental myocardial infarction. Coronary artery ligation was performed in conscious rats and ECG was recorded for 15 min following ligation. Neither metoprolol (2 mg/kg i.p., 20 min before coronary artery ligation), nor glibenclamide (5 mg/kg i.p., 30 min before ligation) pretreatment increased significantly the survival rate during the acute phase of myocardial infarction (10 % and 22 %, respectively vs. 9 % in controls). Combination of glibenclamide with metoprolol, however, significantly improved the survival rate (62 %, P < 0.05). These results suggest that the combination of a cardioselective $beta$-blocking agent with an ATP- dependent potassium channel inhibitor may result in an enhanced antiarrhythmic effect during the acute phase of myocardial infarction.
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- 1. Pogatsa G, Koltai M Z, Balkanyi I, Devai I, Kiss V, Koszeghy A. The effect of various hypoglycaemic sulphonylureas on the cardiotoxicity of glycosides and arrhythmogenic activity due to myocardial ischaemia, Acta Physiol. Hung. 71: 243-250, 1988. 2. Cacciapuoti F, Spiezia R, Bianchi U, Lama D, D’avino M, Varricchio M. Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus, Am. J. Cardiol. 67: 843-847,1991. 3. MacKenzie I, Saville V L, Waterfall J F. Differential class III and glibenclamide effects on action potential duration in guinea-pig papillary muscle during normoxia and hypoxia/ischemia, Br. J. Pharmacol. 110: 531-538, 1993. 4. Wolleben C D, Sanquinetti M C, Siegl P.K.S. Influence of ATP-sensitive potassium modulators on ischemiainduced fibrillation in isolated rat hearts, J. Mol. Cell. Cardiol. 21: 783-788, 1989. 5. Kantor P F , Coetzee W A , Carmeliet E E, Dennis S C, Opie L H. Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulphonylurea, Circ. Res. 66: 478-485, 1990. 6. D’Alonzo A J, Darbenzio R B, Hess T A, Sewter J C, Sleph P G, Grover G J. Effects of potassium on the action of the KATP modulators cromakalim, pinacidil, or glibenclamide on arrhythmias in isolated perfused rat heart subjected to regional ischaemia, Cardiovasc. Res. 28: 881-887, 1994. 7. Tosaki A, Szerdahelyi P, Engelman R M, Das D K. Potassium channel openers and blockers: do they possess proarrhythmic or antiarrhythmic activity in ischemic and reperfused rat hearts? J. Pharmacol. Exp. Ther. 267: 1355- 1362,1993. 8. Baczk I, Leprn I, Papp J Gy, K-ATPchannel modulators increase survival rate during coronary occlusionreperfusion in anaesthetised rats, European J. Pharmacol. 324: 77-83, 1997. 9. Bozdogan
, Leprn I, Papp J Gy. Effect of glimepride and glibenclamide, inhibitors of ATP dependent K+ channel, on ischemia-reperfusion induced arrhythmias in rats, Acta Physiol. Hung. 84: 265-266, 1996. 10. Leprn I, Baczk I, Varr A, Papp J Gy. ATP-sensitive potassium channel modulators: Both pinacidil and glibenclamide produce antarrhythmic activity during acute myocardial infarction in conscious rats, J. Pharmacol. Exp. Ther. 273: 1215- 1220, 1996. 11. Bril A, Man R Y K. Effects of the potassium channel activator, BRL 34915, on the action potential characteristics of canine cardiac purkinje fibers, J. Pharmacol. Exp. Ther. 253: 1090-1096, 1990. 12. Rees S A, Curtis M J. Pharmacological analysis in rat of the role of the ATPsensitive potassium channel as a potential target for antifibrillatory intervention in acute myocardial ischaemia. J. Cardiovasc. Pharm. 26: 280-288, 1995. 13. Escande D, Cavero I, K+ channel openers and ’natural’ cardioprotection, Trends Pharmacol. Sci. 13: 269-272, 1992. 14. Leprn I, Koltai M, Siegmund W, Szekeres L. Coronary artery ligation early arrhythmias and determination of the ischemic area in conscious rats, J. Pharmacol. Meth. 9: 219-230, 1983. 15. Nachlas M M. and Shnitka T K. Macroscopic identification of early myocardial infarct by alterations in dehydrogenase activity, Am. J. Pathol. 42: 379-405, 1963. 16. Walker M J A, Curtis M J, Hearse D J. Campbell R.W.F., Janse M.J., Yellon D M, Cobbe S M, Coker S J, Harness J B. Harron D.W.G. et al., The Lambeth Conventions: guidelines for the study of arrhythmias in ischemia, infarction, and reperfusion. Cardiovasc. Res. 22: 447- 455, 1988.
- 17. Wallenstein S, Zucher C L, Fleiss J L. Some statistical methods useful in circulation research, Circ. Res. 47: 1-9, 1980. 18. Wainwright C L, Parratt J R. The effect of -adrenoceptor blockade and of thromboxane synthetase inhibition, alone and in combination, on arrhythmias resulting from myocardial ischaemia, Adv. Myocardiol. 6: 573- 584, 1985. 19. Leprn I, Parratt J R, Szekeres L. Wainwright C.L., The effects of metoprolol and dazmegrel, alone and in combination, on arrhythmias induced by coronary artery occlusion in conscious rats, Br. J. Pharmac. 86: 229-234, 1985. 20. Siegmund W, Leprn I, Szekeres L. Effect of pentobarbitone anesthesia, age and sex in the acute phase of myocardial infarction in rats, in: Tardos L, Szekeres L, Papp J Gy (Eds.), Pharmacological Control of Heart and Circulation, Akadmiai Kiad, Pergamon Press, Budapest Ð Oxford, 1980, pp. 63-66. 21. Janse M, Wit A L. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction, Physiol. Rev. 69: 1049- 1169, 1989. 22. Ruiz Petrich E, Ponce Zumino A. Schanne O.F., Early action potential shortening in hypoxic hearts: role of chloride current(s) mediated by catecholamine release, J. Mol. Cell. Cardiol. 28: 279-290, 1996. 23. Sundaresan P, Lykos D, Daher A, Diamond T, Morris R, Howes L G. Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM, Diabetes Care 20: 692-697, 1997. 24. Van Staa T, Abenhaim L, Monette J. Rates of hypoglycemia in users of sulfonylureas, J. Clin. Epidemiol. 50: 735-741, 1997.