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CLINICAL RESEARCH: HEART FAILURE

Growth hormone prolongs survival in experimental postinfarction heart failure

Antonio Cittadini, MD^*, J.örgen Isgaard, MD, Maria Gaia Monti, PhD^*, Cosma Casaburi, MD^*, Angela Di Gianni, MD^*, Raffaella Serpico, MD^*, Guido Iaccarino, MD^* and Luigi Saccà, MD^*,*

^* Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Naples, Italy
Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden

Manuscript received November 19, 2002; revised manuscript received February 27, 2003, accepted March 7, 2003.

^* Reprint requests and correspondence: Dr. Luigi Saccà, Medicina Interna, Via Pansini 5, 80131 Naples, Italy.
sacca{at}unina.it

OBJECTIVES: We evaluated the effects of growth hormone (GH) on survival in experimental heart failure (HF).

BACKGROUND: Growth hormone has been beneficial in various models of experimental HF. Whether GH also affects HF progression and survival is not known.

METHODS: A total of 119 rats with moderate myocardial infarction were randomized to receive either GH (3.5 mg/kg every other day) or placebo for 28 days. Treatment was initiated one month after coronary ligation; the follow-up lasted 13 months. In the surviving animals, Doppler echocardiography and closed-chest Millar left ventricular (LV) catheterization were performed. Apoptosis, collagen volume fraction, and capillary density in the LV zone remote from infarction were measured. The early effects of GH on apoptosis were also assessed in a subgroup of eight infarcted rats, treated as specified earlier and euthanized at one month.

RESULTS: Survival rate was 68% in GH-treated rats and 48% in the placebo group (p = 0.0377). Growth hormone had no effect on myocardial architecture, systolic function, and sarcoplasmatic reticulum calcium ATPase-2 messenger ribonucleic acid. Growth hormone improved LV relaxation; this was associated with a 50% reduction in collagen volume fraction and a 27% increase in capillary density. Growth hormone reduced the apoptotic index by 50% at one month and by 33% at 13 months.

CONCLUSIONS: Growth hormone prolonged survival of rats with postinfarction HF. This effect was associated with marked attenuation of cardiomyocyte apoptosis and pathologic interstitial remodeling in the surviving myocardium and enhanced LV relaxation.

Abbreviations and Acronyms   CHF = chronic heart failure   CVF = collagen volume fraction   DNA = deoxyribonucleic acid   GH = growth hormone   HF = heart failure   IGF-I = insulin-like growth factor I   LV = left ventricular   MI = myocardial infarction   RNA = ribonucleic acid   SERCA-2 = sarcoplasmatic reticulum calcium ATPase-2   TUNEL = terminal UTP nick end labeling

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