The effects of ATP-dependent potassium channel opener; pinacidil, and blocker; glibenclamide, on the ischemia induced arrhythmia in partial and complete ligation of coronary artery in rats

Document Type : Original Article


1 Abant Izzet Baysal University, Faculty of Science and Art, Biology Department 14280 Golkoy, Bolu Turkey

2 Duzce University, Faculty of Science and Arts, Biology Department 81620 Konuralp, Duzce Turkey


Objective(s): Electrical inhomogeneity between ischemic and non ischemic myocardium is the basis of arrhythmia which occurs following coronary artery occlusion. The leakage of potassium from the ischemic region to the non ischemic region is very effective in the generation of these arrhythmias. The aim of this study is to research the effect of ATP-dependent potassium (KATP) channel blocker (glibenclamide) and opener (pinacidil) on ischemia induced arrhythmia in the presence of small and large infarct sizes.
Materials and Methods: In this study Sprague-Dawley male rats of 8-9 months of age were used. Ischemia was produced by the partial ligation of left coronary artery ramus descending (PL) for smaller infarct and complete ligation of this artery (CL) for larger infarct for 30 min. The arrhythmia score which was calculated from the duration and type of arrhythmia was significantly higher in animals which had a larger infarct area than the animals which had a smaller infarct.
Results: Glibenclamide increased the rate of arrhythmia in animals having smaller infarct but not in animals having larger infarct. Pinacidil did not affect the occurrence of arrhythmia in either group. There was a significant difference in the infarct size and risk of infarct zone between animals which had small and large infarct sizes. The effect of glibenclamide and pinacidil on the arrhythmias differed depend on decrease of infarct size.
Conclusion: Glibenclamide is not effective to decrease ischemia induced arrhythmia in the presence of small and pinacidil in large ischemic zone.


1. Pokorny J, Stanek V, Vrana M, Sudden Cardiac Death Thirty Years Ago and at present. The role of Autonomic disterbunces in acute myocardial ınfarction revisited. Physiol. Res  2011; 715-728.
2. Harris AS. Potassium and experimental coronary occlusion. Am Heart J 1966; 71: 797-802.
3. Coronel R, Fiolet JW, Wilms-Schopman FJG, Schaapherder AF, Johnson TA, Gettes LS, et al. Distribution of extracellular potassium and its relation to electrophysiological changes during acute myocardial ischemia in the isolated perfused porcine heart. Circulation 1988; 77: 1125-1138.
4. Wilde AAM, Escande D, Schumacher CA, Thuringen D, Mestre M, Fiolet JWT, et al. Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP sensitive potassium channel. Circ Res 1990; 67: 835-843.
5. Billman GE, Avendora CE, Halliwil JR. The effects                  of ATP-dependent potassium channel antagonist, glyburide, on coronary flow and susceptibility to ventricular fibrillation. J Cardiovasc Pharm 1993; 21: 197-207.
6. Colatsky TJ, Argentieri TM. Potassium channel blockers as antiarrhythmic drugs. Drug Develop Res 1994; 33: 235-249.
7. Tosaki A, Hellegouarch A. Adenosine triphosphate sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion induced injury. JACC 1994; 23: 487-496.
8. Lepran I, Baczko I, Varro A, Papp JGy. ATP sensitive potassium channel modulators: Both pinacidil and glibenclamide produce antiarrhythmic activity during acute myocardial infarction in conscious rats. J Pharmacol Exp Ther. 1996; 277: 1215-1220.
9. Bozdogan O. ATP-dependent potassium channel openers and blockers: proarrhythmic or antiarrhythmic effects following myocardial ischemia and reperfusion. Kafkas Univ Vet Fak Derg 1997; 3: 127-133.
10. El-Reyani N, Bozdogan O, Baczko I. Comparison of the efficacy of glibenclamide and glimepride in reperfusion induced arrhythmias in rats. Eur J Pharmacol 1999; 192: 365-187.
11. Bernauer W. Concerning the effect of the KATP channel blocking agent glibenclamide on ischemic and reperfusion arrhythmias. Eur J Pharmacol 1997; 326: 147-156.
12. Del Valle HF, Lascano EC, Negroni JA, Crottogini AJ. Glibenclamide effects on reperfusion-induced malignant arrhythmias and left ventricular mechanical recovery from stunning in conscious sheep. Cardiovasc Res 2001; 50: 474-485.
13. Chi L, Uprichard AC, Lucchesi BR. Profibrillatory actions of pinacidil in a conscious canine model of sudden coronary death. J Cardiovasc Pharm 1990; 15: 452-464.
14. Tosaki A, Szerdahelyi P, Engelman RM. Potassium channel openers and blockers: Do they proarrhyth-mic or antiarrhythmic activity in ischemic and reperfused rat hearts? J Pharmacol Exp Ther 1993; 263: 1261–1268.
15. Wilde AAM. KATP channels openning and arrhythmogenesis. J Cardiovasc Pharm 1994; 24: 35-40.
16. Kerr MJ, Wilson R, Shangs RG. Suppression of ventricular arrhythmias after coronary artery ligation by pinacidil, a vasodilator drug. J Cardiovasc Pharm 1985; 7: 875-883.
17. Baczko I, Lepran I, Papp JGy. KATP channel modulators increase survival rate during coronary occlusion-reperfusion in anaesthetized rats. Eur J Pharmacol 1997; 324: 77–83.
18. Bozdogan O, Gonca E, Nebigil M, Tiryaki ES. Effect of thimerosal on arrhythmia induced by coronary ligation. Int Heart J 2005; 46: 711-721.
19. Bozdogan O, Bolukbası F. The arrhythmias occuring in the late period of experimentally induced myocardial infarction in dogs. Turk J Vet Anim Sci 1994; 8: 147–151.
20. Lepran I, Koltai M, Siegmund W, Skekeres L. Coronary artery ligation, early arrhythmias and determination of the ischemic area in conscious rats. J Pharmacol Method 1983; 9: 219-230.
21. Gonca E, Bozdogan O. Both mitochondrial                    KATP channel opening and sarcolemmal KATP channel blockage confer protection against ischemia/-reperfusion- induced arrhythmia in anesthetized male rats. J Cardiovasc Pharm 2010; 15: 403-411.
22. Walker MJ, Curtis MJ, Hearse DJ, Campbell RW, Janse MJ, Yellon DM, et al. The Lambeth Conventions: guidelines for the study of arrhythmias in ischaemia infarction, and reperfusion. Cardiovasc
Res 1988 Jul; 22:447-55.
23. Gonca E, Tiryaki SE, Bozdogan O. The effect of sex on the ischemia– reperfusion arrhythmias and the role of ATP-dependent potassium channel blockage. Turk J Biol 2004; 28: 39-46.
24. McKensie I, Saville VL, Waterfall JF. Differential class III and glibenclamide effects on action potential duration in guinapig papillary muscle during normoxia and hypoxia/ischemia. Brit J Pharmacol 1993; 110: 531-583.
25. Tweedie D, Henderson C, Kane K. Glibenclamide, but not class 3 drugs, prevents ischemic shortening of the refractory period in guinea-pig hearts. Eur J Pharmacol 1993; 240: 251-257.
26. Escande D, Cavero L. K+ channel openers and natural cardioprotection. Trends Pharmacol Sci 1992; 13: 269–272.
27. Bozdogan O, Lepran I, Papp JGy. Effect of the combination of glibenclamide, an ATP-dependent potassium channel blocker, and metaprolol, a cardioselective β-adrenoceptor blocker, during myocardial infarction in conscious rats. Turk J Med Sci 2000; 30: 517-522.