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4 Protective role of growth hormone secretagogues against myocardial dysfunction in mouse models of myocardial ischemia reperfusion and infarction
  1. H McDonald1,
  2. ND Kurniawan2,
  3. J Peart3,
  4. C Chen1
  1. 1School of Biomedical Sciences, The University of Queensland, Brisbane, Australia
  2. 2Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia
  3. 3Heart Foundation Research Centre, Griffith University, Gold Coast, Australia

Abstract

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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