Sarkolemmal ve mitokondriyal ATP bağımlı potasyum kanallarının erkek ve dişi sıçanlarda iskemi ve reperfüzyon aritmilerine etkisi; Endojen östrojenin rolü

The role of ATP dependent potassium channel in ischemia reperfusion induced injury and arrhythmias have been investigated intensively, however the effect of sarcolemmal and mitochondrial ATP dependent potassium channel modulation by drugs on these arrhythmias remains controversial. Therefore, the aim of the present study is to investigate the role of sarcolemmal and mitochondrial KATP channel modulation on ischemia and reperfusion induced arrhythmias.In this study 143 Sprague-Dowley rats in male and female aged 7-8 months old were used. Six minutes ischemia and six minutes reperfusion was generated by the ligation and releasing of left coronary artery. The effect of pinacidil, HMR 1098, 5-HD and diazoxide on ischemia reperfusion induced arrhythmia have been examined.The score of arrhythmia in reperfusion and total duration of arrhythmias in ligation was found to be lower in female and ovariectomized female than in male rats (P<0.05). The score of arrhythmias and total length of arrhythmias in males during reperfusion was lower in pinacidil, HMR 1098, 5-HD and diazoxide groups compared to control (P<0.05). Pinacidil did not decrease the score of arrhythmia in males during reperfusion when it was combined with 5-HD (P<0.05). In females, the combination of Pinacidil and HMR 1098 decreased total length of arrhythmias during reperfusion (P<0.05). In ovariectomized females, HMR 1098 decreased the score of arrhythmias during reperfusion while 5-HD increased duration of total arrhythmias during ligation (P>0.05).The lower arrhythmia scores observed in female did not depend on the circulating estrogen levels. The ovariectomy changed the response of females to HMR 1098 and 5-HD. It may indicate estrogen involvement in the modulation of KATP channel by selective drugs. Both activation and inhibition of mitochondrial or sarcolemmal KATP channel produced antiarrhythmia in males. The protective effect of pinacidil against arrhythmia was abolished by the combination of pinacidil with mitochondrial KATP channel blocker, That may suggest that pinacidil decreases arrhythmia through mitochondrial potassium channel opening.As a conclusion, both the blockage of sarcolemmal KATP dependent channel and opening of mitochondrial KATP channel at the same time may be effective to decrease ischemia reperfusion induced arrhythmia.Key Words: Ischemia reperfusion, Arrhythmias, Rat, Sex, ATP dependent potassium channels, Estrogen, Pinacidil, HMR 1098, 5-HD, Diazoxide.