Hexarelin treatment preserves myocardial function and reduces cardiac fibrosis in a mouse model of acute myocardial infarction

Ischemic heart disease ( IHD ) is a leading cause of morbidity and mortality worldwide. Growth hormone secretagogues ( GHS ) have been shown to improve cardiac function in models of IHD . This study determined whether hexarelin ( HEX ), a synthetic GHS , preserves cardiac function and morphology in a mouse model of myocardial infarction ( MI ). MI was induced by ligation of the left descending coronary artery in C57 BL /6J mice followed by vehicle ( VEH ; n  = 10) or HEX (0.3 mg/kg/day; n  = 11) administration for 21 days. MI ‐injured and sham mice (treated with VEH ; n  = 6 or HEX ; n  = 5) underwent magnetic resonance imaging for measurement of left ventricular ( LV ) function, mass and infarct size at 24 h and 14 days post‐ MI . MI ‐ HEX mice displayed a significant improvement ( P  < 0.05) in LV function compared with MI ‐ VEH mice after 14 days treatment. A significant decrease in LV mass, interstitial collagen and collagen concentration was demonstrated with chronic HEX treatment (for 21 days), accompanied by a decrease in TGF ‐ β 1 expression, myofibroblast differentiation and an increase in collagen‐degrading MMP ‐13 expression levels. Furthermore, heart rate variability analysis demonstrated that HEX treatment shifted the balance of autonomic nervous activity toward a parasympathetic predominance and sympathetic downregulation. This was combined with a HEX ‐dependent decrease in troponin‐I, IL ‐1 β and TNF ‐ α levels suggestive of amelioration of cardiomyocyte injury. These results demonstrate that GHS may preserve ventricular function, reduce inflammation and favorably remodel the process of fibrotic healing in a mouse model of MI and hold the potential for translational application to patients suffering from MI .