Effects of Acute and Chronic Administration of Erythropoietin on Arrhythmias Induced by Myocardial Ischemia and Preconditioning in Anesthetized Rats

Şeniz Demiryürek; Ali Fuad Kara; Cahit Bağcı; İbrahim Sarı; Mehmet Tarakçıoğlu; A. Tuncay Demiryürek

doi:10.58600/eurjther.2010-16-3-1220-arch

Authors

Şeniz Demiryürek Gaziantep Üniversitesi Tıp Fakültesi Fizyoloji Anabilim Dalı
Ali Fuad Kara Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji Anabilim Dalı
Cahit Bağcı Gaziantep Üniversitesi Tıp Fakültesi Fizyoloji Anabilim Dalı
İbrahim Sarı Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı
Mehmet Tarakçıoğlu Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Biyokimya Anabilim Dalı
A. Tuncay Demiryürek Gaziantep Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji Anabilim Dalı

DOI:

https://doi.org/10.58600/eurjther.2010-16-3-1220-arch

Keywords:

Arrhythmias, Erythropoietin, Ischemia, Carbachol, Nitric oxide, Preconditioning

Abstract

Erythropoietin is a cytokine that is commonly associated with its role as a hormonal stimulator of erythropoiesis. Recombinant human erythropoietin is used to correct anemia in patients undergoing chronic hemodialysis. Ischemic preconditioning is a powerful endogenous protective phenomenon in which brief episodes of ischemia induce protection against future, lethal ischemia. Despite the intensive investigation, the exact molecular mechanisms underlying ischemic preconditioning are not well known. Erythropoietin has been suggested as another endogenous mediator of ischemic preconditioning since it is produced after ischemic or hypoxic insults. In order to determine its cardioprotective effects, we examined the effects of acute and chronic administration of erythropoietin on occlusion-induced arrhythmias in anesthetized rats in the present study. Erythropoietin produced marked antiarrhythmic effects with reduction in ventricular tachycardia, abolition of ventricular fibrillation and attenuation of arrhythmia scores. üur results showed that erythropoietin itself was able to induce preconditioning and preserved the cardioprotective effects of ischemic and carbachol-induced pharmacological preconditioning. Chronic erythropoietin administration generated hypertension and this effect was markedly augmented in the presence of Nü synthase inhibitor L-NAME. However, L-NAME did not inhibit the cardioprotective effects of erythropoietin in anesthetized rats. Although plasma Nü levels was markedly reduced with L-NAME, chronic erythropoietin led to an increased in Nü levels. Erythropoietin could also act protectively by upregulating enzymes that scavenge oxygen radicals. Therefore, erythrocyte superoxide dismutase enzyme levels were measured in the present study, but no changes were observed. There were marked inhibitions in malondialdehyde and lactate levels in all groups when compared to control. These results suggest that erythropoietin is able to protect heart against ventricular arrhythmias and can produce cardiac preconditioning.

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