Abstract 18122: Reduction of Scar Tissue after GHRH-Agonist Treatment in a Swine Model of Sub-acute Ischemic Cardiomyopathy
Introduction: Growth hormone-releasing hormone receptor agonists (GHRH-A) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart.
Hypothesis: We tested the hypothesis that the administration of GHRH-A prevents ventricular remodeling in a swine sub-acute MI model.
Methods: Twelve female Yorkshire swine (25-30 Kg) underwent transient occlusion of the LAD coronary artery (MI). Two-weeks post-MI, swine were randomized to receive injections of either 30 μg/Kg GHRH-A (MR-409) (GHRH-A group; n=6) or vehicle (placebo group; n=6). Cardiac MRI, pressure volume loops and measures of endothelial function were obtained at multiple time points. Infarct-, border- and remote- (non-infarcted) zones were assessed for growth hormone-releasing hormone receptor (GHRHR) by immunohistochemistry.
Results: Four-weeks of GHRH-A treatment resulted in reduced scar mass (GHRH-A: –21.9±6.42%; p=0.02; placebo: 10.9±5.88%; p=0.25; Two-way ANOVA; p=0.003), and scar size (percent of left ventricle mass) (GHRH-A: –38.38±4.63; p=0.0002; placebo: –14.56± 6.92; p=0.16; Two-way ANOVA; p=0.02). Moreover, peripheral endothelial function increased in following GHRH-A treatment (paired t-test; p=0.006) but not in the placebo group (p=0.99). Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure-volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH-A group compared to the placebo group.
Conclusions: Daily subcutaneous administration of GHRH-A is feasible and safe in female swine. Furthermore, GHRH-A therapy significantly reduced infarct size and increased endothelial function, suggesting a local activation of the GHRH pathway leading to the reparative process and preservation of peripheral endothelial functions.
Author Disclosures: L. Lima Bagno: None. R. Kanashiro-Takeuchi: None. V. Suncion: None. S. Golpanian: None. V. Karantalis: None. A. Wolf: None. B. Wang: None. C. Premer: None. W. Balkan: None. J. Rodriguez: None. D. Valdes: None. M. Rosado: None. N. Block: None. P. Goldstein: None. A. Morales: None. A. Schally: None. J.M. Hare: Employment; Modest; Vestion. Ownership Interest; Modest; Biscayne. Ownership Interest; Significant; Vestion Inc.
- © 2014 by American Heart Association, Inc.