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The Growth Hormone Secretagogue Hexarelin Improves Cardiac Function in Rats after Experimental Myocardial Infarction¹

Research Center for Endocrinology and Metabolism, the Department of Internal Medicine (Å.T., B.-Å.B., J.I.), Wallenberg Laboratory (E.B., Å.H.), the Department of Clinical Physiology (K.C., V.K.), and the Department of Clinical Pharmacology (X.Y.S., T.H.), Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden

Address all correspondence and requests for reprints to: Jörgen Isgaard, M.D., Ph.D., Research Center for Endocrinology and Metabolism, Gröna Stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: jorgen.isgaard{at}ss.gu.se

Several studies have shown that GH can enhance cardiac performance in rats after experimental myocardial infarction and in humans with congestive heart failure. In the present study, the hemodynamic effects of hexarelin (Hex), an analog of GH-releasing peptide-6 and a potent GH secretagogue, were compared with the effects of GH. Four weeks after ligation of the left coronary artery male rats were treated sc twice daily with hexarelin [10 µg/kg·day (Hex10) or 100 µg/kg·day (Hex100)], recombinant human GH (2.5 mg/kg·day), or 0.9% NaCl for 2 weeks. Transthoracic echocardiography was performed before and after the treatment period. GH, but not Hex, increased body weight gain. GH and Hex100 decreased total peripheral resistance (P < 0.05) and increased stroke volume (P < 0.05 and P < 0.01, respectively) and stroke volume index (P = 0.06 and P < 0.01, respectively) vs. NaCl. Cardiac output was increased by GH and Hex100 (P < 0.05), and cardiac index was increased by Hex100 with a borderline significance for GH (P = 0.06). In conclusion, Hex improves cardiac function and decreases peripheral resistance to a similar extent as exogenous GH in rats postmyocardial infarction. The mechanisms of these effects are unclear; they could be mediated by GH or a direct effect of Hex on the cardiovascular system.

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