One Dose of Ghrelin Prevents the Acute and Sustained Increase in Cardiac Sympathetic Tone after Myocardial Infarction

Abstract

Acute myocardial infarction (MI) increases sympathetic nerve activity (SNA) to the heart, which exacerbates chronic cardiac deterioration. The hormone ghrelin, if administered soon after an MI, prevents the increase in cardiac SNA and improves early survival prognosis. Whether these early beneficial effects of ghrelin also impact on cardiac function in chronic heart failure has not yet been addressed and thus was the aim of this study. MI was induced in Sprague Dawley rats by ligating the left coronary artery. One bolus of saline (n = 7) or ghrelin (150 μg/kg, sc, n = 9) was administered within 30 min of MI. Two weeks after the infarct (or sham; n = 7), rats were anesthetized and cardiac function was evaluated using a Millar pressure-volume conductance catheter. Cardiac SNA was measured using whole-nerve electrophysiological techniques. Untreated-MI rats had a high mortality rate (50%), evidence of severe cardiac dysfunction (ejection fraction 28%; P < 0.001), and SNA was significantly elevated (102% increase; P = 0.03). In comparison, rats that received a single dose of ghrelin after the MI tended to have a lower mortality rate (25%; P = NS) and no increase in SNA, and cardiac dysfunction was attenuated (ejection fraction of 43%; P = 0.014). This study implicates ghrelin as a potential clinical treatment for acute MI but also highlights the importance of therapeutic intervention in the early stages after acute MI. Moreover, these results uncover an intricate causal relationship between early and chronic changes in the neural control of cardiac function in heart failure.