Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine With subacute ischemic cardiomyopathy

Luiza L. Bagno, Rosemeire Takeuchi, Viky Y. Suncion, Samuel Golpanian, Vasileios Karantalis, Ariel Wolf, Bo Wang, Courtney Premer, Wayne E Balkan, Jose Rodriguez, David Valdes, Marcos Rosado, Norman L Block, Peter Goldstein, Azorides R Morales, Ren Zhi Cai, Wei Sha, Andrew V Schally, Joshua Hare

Research output: Contribution to journalArticle

12 Citations (Scopus)

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. Methods and 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 lg/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.

Original languageEnglish (US)
Article numbere001464
JournalJournal of the American Heart Association
Volume4
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Growth Hormone-Releasing Hormone
Cardiomyopathies
Cicatrix
Swine
Myocardial Infarction
Placebos
Analysis of Variance
Pressure
Ventricular Remodeling
Coronary Vessels
Animal Models
Hemodynamics
Immunohistochemistry
Magnetic Resonance Imaging
Injections
Therapeutics
somatotropin releasing hormone receptor

Keywords

  • Diastolic function
  • Growth hormone-releasing hormone
  • Heart failure
  • Myocardial infarction
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine With subacute ischemic cardiomyopathy. / Bagno, Luiza L.; Takeuchi, Rosemeire; Suncion, Viky Y.; Golpanian, Samuel; Karantalis, Vasileios; Wolf, Ariel; Wang, Bo; Premer, Courtney; Balkan, Wayne E; Rodriguez, Jose; Valdes, David; Rosado, Marcos; Block, Norman L; Goldstein, Peter; Morales, Azorides R; Cai, Ren Zhi; Sha, Wei; Schally, Andrew V; Hare, Joshua.

In: Journal of the American Heart Association, Vol. 4, No. 4, e001464, 2015.

Research output: Contribution to journalArticle

Bagno, LL, Takeuchi, R, Suncion, VY, Golpanian, S, Karantalis, V, Wolf, A, Wang, B, Premer, C, Balkan, WE, Rodriguez, J, Valdes, D, Rosado, M, Block, NL, Goldstein, P, Morales, AR, Cai, RZ, Sha, W, Schally, AV & Hare, J 2015, 'Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine With subacute ischemic cardiomyopathy', Journal of the American Heart Association, vol. 4, no. 4, e001464. https://doi.org/10.1161/JAHA.114.001464
Bagno, Luiza L. ; Takeuchi, Rosemeire ; Suncion, Viky Y. ; Golpanian, Samuel ; Karantalis, Vasileios ; Wolf, Ariel ; Wang, Bo ; Premer, Courtney ; Balkan, Wayne E ; Rodriguez, Jose ; Valdes, David ; Rosado, Marcos ; Block, Norman L ; Goldstein, Peter ; Morales, Azorides R ; Cai, Ren Zhi ; Sha, Wei ; Schally, Andrew V ; Hare, Joshua. / Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine With subacute ischemic cardiomyopathy. In: Journal of the American Heart Association. 2015 ; Vol. 4, No. 4.
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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. Methods and 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 lg/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.",
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author = "Bagno, {Luiza L.} and Rosemeire Takeuchi and Suncion, {Viky Y.} and Samuel Golpanian and Vasileios Karantalis and Ariel Wolf and Bo Wang and Courtney Premer and Balkan, {Wayne E} and Jose Rodriguez and David Valdes and Marcos Rosado and Block, {Norman L} and Peter Goldstein and Morales, {Azorides R} and Cai, {Ren Zhi} and Wei Sha and Schally, {Andrew V} and Joshua Hare",
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T1 - Growth hormone-releasing hormone agonists reduce myocardial infarct scar in swine With subacute ischemic cardiomyopathy

AU - Bagno, Luiza L.

AU - Takeuchi, Rosemeire

AU - Suncion, Viky Y.

AU - Golpanian, Samuel

AU - Karantalis, Vasileios

AU - Wolf, Ariel

AU - Wang, Bo

AU - Premer, Courtney

AU - Balkan, Wayne E

AU - Rodriguez, Jose

AU - Valdes, David

AU - Rosado, Marcos

AU - Block, Norman L

AU - Goldstein, Peter

AU - Morales, Azorides R

AU - Cai, Ren Zhi

AU - Sha, Wei

AU - Schally, Andrew V

AU - Hare, Joshua

PY - 2015

Y1 - 2015

N2 - 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. Methods and 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 lg/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.

AB - 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. Methods and 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 lg/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.

KW - Diastolic function

KW - Growth hormone-releasing hormone

KW - Heart failure

KW - Myocardial infarction

KW - Remodeling

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