Growth hormone secretagogues (GHS) have been shown to possess cardioprotective properties in ischaemic heart disease models. This study aimed to determine whether hexarelin, a synthetic GHS, preserves cardiac function in models of myocardial infarction (MI). MI was induced by permanent ligation of the left descending coronary artery (LAD) in C57BL/6J mice (n = 44). In a second group (n = 39), the LAD was transiently ligated, followed by reperfusion. Vehicle or hexarelin was administered at 0.3 mg/kg/day subcutaneously. Treated and sham mice were subjected to magnetic resonance imaging using a T1-weighted late gadolinium enhancement sequence (LGE) at 9.4 Tesla (T) to measure ventricular function and tissue characteristics at 24 h and 21 days post-LAD ligation. Infarct size and area-at-risk was confirmed using ex-vivo analysis at 16.4T using a 3D T1/T2*-weighted sequence using iron nanoparticles and LGE. Hexarelin-treated mice demonstrated a significant improvement (P < 0.05) in ejection fraction (EF) compared with vehicle mice at 24 h in both the permanent ligation (44.7% vs 37.1%) and reperfused (56.9% vs 49.8%) groups. After 21 days there were no significant differences in EF between sham and hexarelin-treated mice in the reperfused group, hexarelin mice showed a significant improvement in EF compared to vehicle mice (65.1% vs 56.7%). A decreasing trend in infarct size was observed in hexarelin-treated mice acutely; experiments are being completed to determine chronic infarct size. These results indicate that GHS may preserve ventricular function in models of MI and are the first to demonstrate a potential therapeutic effect of GHS against myocardial reperfusion injury in vivo.
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