Abstract 15309: Ghrelin Protects Heart Against Ischemia-Induced Arrhythmias by Preserving Connexin43 Protein
Background: Vagal nerve stimulation has been postulated to contribute to the antifibrillatory effect. Recently we have shown that ghrelin modulates cardiac autonomic activity and attenuates early left ventricular remodeling in rats with myocardial infarction. In the present study, we hypothesized that ghrelin administration would exert antiarrhythmic effects via the modulation of autonomic nerve activity in rats with acute myocardial ischemia (MI).
Methods and Results: Male Sprague-Dawley rats were exposed to a 30-minte period of ischemia induced by ligation of the left coronary artery. They were randomized to receive ghrelin (n=26) or saline (n=26) during coronary ligation. Administration of ghrelin increased the high-frequency (HF) power and decreased the low-freequency (LF)/HF ratio of heart rate variability. Ventricular tachyarrhythmia occurred less frequently in rats with MI receiving ghrelin compared to rats receiving saline. Immunoblotting revealed that MI rats with saline showed a marked reduction in the amount of phosphorylated connexin43 (Cx43) in left ventricles, whereas MI rats with ghrelin showed only a slight reduction compared to rats with sham operation. Immunohistochemistry confirmed that the MI-induced-loss of Cx43 was prevented by ghrelin administration. These effects of ghrelin were diminished by co-administration of atropine. Interestingly, blockade of the vagal afferent also abolished the antiarrhythmic effect of ghrelin.
Conclusions: Ghrelin administration reduced ventricular arrhythmia accompanied by prevention of the loss of Cx43 during acute MI. This beneficial effect of ghrelin might be mediated by the modulation of cardiac autonomic nerve activity. These data suggest the potential usefulness of ghrelin as a new antiarrhythmic agent.
- © 2010 by American Heart Association, Inc.