title: Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine with subacute ischemic cardiomyopathy.
abstract: BACKGROUND
  Growth hormone-releasing hormone agonists (GHRH-As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-As prevents ventricular remodeling in a swine subacute MI model.
  
  
  RESULTS
  Twelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending 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 magnetic resonance imaging and pressure-volume loops were obtained at multiple time points. Infarct, border, and remote (noninfarcted) zones were assessed for GHRH receptor by immunohistochemistry. 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; 2-way ANOVA; P=0.003), and scar size (percentage of left ventricular mass) (GHRH-A: -38.38 ± 4.63; P=0.0002; placebo: -14.56 ± 6.92; P=0.16; 2-way ANOVA; P=0.02). This was accompanied by improved diastolic strain. 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 with the placebo group.
  
  
  CONCLUSIONS
  Daily subcutaneous administration of GHRH-A is feasible and safe in a large animal model of subacute ischemic cardiomyopathy. Furthermore, GHRH-A therapy significantly reduced infarct size and improved diastolic strain, suggesting a local activation of the GHRH pathway leading to the reparative process.
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Luiza L
authors.initials: LL
authors.lastname: Bagno
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.) Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL (R.M.K.T., C.P., J.M.H.).
authors.forename: Rosemeire M
authors.initials: RM
authors.lastname: Kanashiro-Takeuchi
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Viky Y
authors.initials: VY
authors.lastname: Suncion
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Samuel
authors.initials: S
authors.lastname: Golpanian
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Vasileios
authors.initials: V
authors.lastname: Karantalis
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Ariel
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.) Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL (R.M.K.T., C.P., J.M.H.).
authors.forename: Courtney
authors.initials: C
authors.lastname: Premer
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Wayne
authors.initials: W
authors.lastname: Balkan
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: David
authors.initials: D
authors.lastname: Valdes
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.).
authors.forename: Marcos
authors.initials: M
authors.lastname: Rosado
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.) Bruce A. Carter Miami Veterans Affairs Healthcare System, Miami, FL (N.L.B., R.Z.C., W.S., A.V.S.).
authors.forename: Norman L
authors.initials: NL
authors.lastname: Block
authors.affiliation: Biscayne Pharmaceuticals Inc, Miami, FL (P.G.).
authors.forename: Peter
authors.initials: P
authors.lastname: Goldstein
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.).
authors.forename: Azorides
authors.initials: A
authors.lastname: Morales
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.) Bruce A. Carter Miami Veterans Affairs Healthcare System, Miami, FL (N.L.B., R.Z.C., W.S., A.V.S.).
authors.forename: Ren-Zhi
authors.initials: RZ
authors.lastname: Cai
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.) Bruce A. Carter Miami Veterans Affairs Healthcare System, Miami, FL (N.L.B., R.Z.C., W.S., A.V.S.).
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.) Bruce A. Carter Miami Veterans Affairs Healthcare System, Miami, FL (N.L.B., R.Z.C., W.S., A.V.S.).
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL (L.L.B., R.M.K.T., V.Y.S., S.G., V.K., A.W., B.W., C.P., W.B., J.R., D.V., M.R., J.M.H.) Department of Medicine, University of Miami Miller School of Medicine, Miami, FL (N.L.B., A.M., R.Z.C., W.S., A.V.S., J.M.H.) Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL (R.M.K.T., C.P., J.M.H.).
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000188:drug therapy* / Q000473:pathology; D052279:Creatine Kinase, MB Form / Q000097:blood; D052283:Creatine Kinase, MM Form / Q000097:blood; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000819:agonists* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D009203:Myocardial Infarction / Q000150:complications* / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D017337:Sermorelin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013552:Swine; D019210:Troponin I / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: C000606705:GHRH(1-29)N-CH3, N-Me-Tyr(1)-Ala(2)-Orn(12)-Abu(15)-Orn(21)-Nle(27)-Asp(28)-; D019210:Troponin I; D017337:Sermorelin; D013007:Growth Hormone-Releasing Hormone; D052279:Creatine Kinase, MB Form; D052283:Creatine Kinase, MM Form
keywords: diastolic function; growth hormone–releasing hormone; heart failure; myocardial infarction; remodeling
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