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J Am Coll Cardiol, 2002; 39:90-95
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY

Growth hormone corrects vascular dysfunction in patients with chronic heart failure

Raffaele Napoli, MD*, Vincenzo Guardasole, MD*, Margherita Matarazzo, MD*, Emiliano A. Palmieri, MD*, Ugo Oliviero, MD*, Serafino Fazio, MD* and Luigi Saccà, MD*,*

* Department of Internal Medicine and Cardiovascular Sciences, University Federico II School of Medicine, Naples, Italy

Manuscript received June 12, 2001; revised manuscript received September 4, 2001, accepted September 7, 2001.

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

OBJECTIVES: The goal of this study was to test the hypothesis that growth hormone (GH) administration to patients with chronic heart failure (CHF) corrects their vascular dysfunction.

BACKGROUND: Endothelial dysfunction is a prominent feature of CHF. Recent evidence indicates that GH plays a role in vascular reactivity.

METHODS: We studied vascular reactivity in 16 patients with CHF (New York Heart Association class II to III) before and after three months of GH (4 IU subcutaneously every other day) or placebo administration in a randomized, double-blind trial. We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial, graded infusion of acetylcholine (ACh) and sodium nitroprusside (NP). We also measured the forearm balance of nitrite and cyclic guanosine monophosphate (cGMP) before and during ACh infusion. Maximal oxygen uptake (VO2max) was measured by breath-to-breath respiratory gas analysis.

RESULTS: Before treatment, the response of FBF to ACh was flat (p = NS). Growth hormone, but not placebo, greatly improved this response (p = 0.03) and, concomitantly, increased the forearm release of nitrite and cGMP (p < 0.05). Growth hormone also potentiated the FBF response to NP (p = 0.013). Growth hormone interacted with ACh response (p = 0.01) but not with the response to NP (p = NS). Accordingly, GH enhanced the slope of the dose-response curve to ACh (p < 0.05) but not to NP. The VO2max increased significantly after GH treatment (20 ± 2 and 26 ± 2 ml ·Kg–1· min–1 before and after GH treatment, respectively, p < 0.05) but not after placebo.

CONCLUSIONS: A three-month treatment with GH corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation in patients with CHF. The data highlight the potential role of GH in the progression of congestive heart failure.

Abbreviations and Acronyms
  ACh
  acetylcholine
  cGMP
  cyclic guanosine monophosphate
  CHF
  chronic heart failure
  FBF
  forearm blood flow
  GH
  growth hormone
  IGF-I
  insulin-like growth factor I
  L-NMMA
  L-N-monomethylarginine
  LV
  left ventricular
  NYHA
  New York Heart Association
  NO
  nitric oxide
  NP
  sodium nitroprusside
  PVR
  peripheral vascular resistance
  VO2max
  maximal oxygen uptake




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