Early Ghrelin Treatment after Myocardial Infarction Prevents an Increase in Cardiac Sympathetic Tone and Reduces Mortality

Abstract

Acute myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (CSNA), which ultimately exacerbates chronic cardiac dysfunction. Ghrelin (Ghr), a GH-releasing peptide, is an effective treatment for improving cardiac function in chronic heart failure. Ghr also suppresses renal sympathetic nerve activity (SNA) and, therefore, may have important therapeutic benefits in the early stages of acute MI: by reducing CSNA. In this study we hypothesized that early Ghr administration may prevent an increase in CSNA in the acute phase after MI. CSNA was continuously recorded in urethane-anaesthetized rats before and for 5 h after acute MI (or sham). MI was induced by ligation of the left anterior descending coronary artery. Rats received an injection of either saline or Ghr (150 microg/kg, sc) 1 min, or 2 h, after the infarct. CSNA remained stable during the 5-h recording duration in sham rats. MI induced a maximal 110% increase in SNA, which was prevented in rats that received Ghr 1 min after infarct. When Ghr was injected 2 h after MI (SNA had increased by approximately 85%), SNA decreased to pre-MI activity. Importantly, early Ghr administration significantly reduced the high mortality rate associated with MI (61% mortality in untreated MI rats cf. approximately 23% in Ghr-treated MI rats). These results show that early Ghr treatment prevents the increase in CSNA after MI, which may contribute to the improved chances of survival. Whether these early beneficial effects of Ghr also have long-term benefits for improving cardiac function is an area that requires further investigation.