Differential cardiac effects of growth hormone and insulin-like growth factor1 in the rat: a combined in vivo and in vitro evaluation

A Cittadini, H Strömer, SE Katz, R Clark, AC Moses… - Circulation, 1996 - Am Heart Assoc
A Cittadini, H Strömer, SE Katz, R Clark, AC Moses, JP Morgan, PS Douglas
Circulation, 1996Am Heart Assoc
Background Despite their increasing clinical use and recent evidence that growth hormone
(GH) and insulin-like growth factor–1 (IGF-1) target the heart, there has been no systematic
investigation of the effects of GH and IGF-1 on the cardiovascular system. Methods and
Results Sixty normal but growing adult female rats were randomized to receive 4 weeks of
treatment with GH (3.5 mg· kg− 1· d− 1), IGF-1 (3 mg· kg− 1· d− 1), a combination of the two,
or placebo. Transthoracic echocardiograms were performed at baseline and at 2 weeks and …
Background Despite their increasing clinical use and recent evidence that growth hormone (GH) and insulin-like growth factor–1 (IGF-1) target the heart, there has been no systematic investigation of the effects of GH and IGF-1 on the cardiovascular system.
Methods and Results Sixty normal but growing adult female rats were randomized to receive 4 weeks of treatment with GH (3.5 mg · kg−1 · d−1), IGF-1 (3 mg · kg−1 · d−1), a combination of the two, or placebo. Transthoracic echocardiograms were performed at baseline and at 2 weeks and 4 weeks of treatment. After the final echocardiography, rats underwent either closed-chest left ventricular (LV) catheterization or Langendorff perfusion studies. Myocyte diameter and interstitial tissue fraction were assessed by morphometric histology. Echocardiographic and ex vivo data demonstrated a LV hypertrophic response in all three groups of treated animals that was most marked in the GH group, which alone exhibited a concentric growth pattern (relative wall thickness, 0.52 versus 0.42 to 0.44 in the other groups; P<.001). At 4 weeks, cardiac index was significantly higher and total systemic vascular resistance was lower in all groups of treated animals than in control animals (both P<.001), whereas arterial blood pressure did not differ significantly. All indexes of in vivo and in vitro cardiac function were higher in GH- and IGF-1–treated rats than in control animals, whereas combination therapy yielded a blunted effect. Myocyte diameter was increased in all three treated groups without an increase in interstitial tissue.
Conclusions Exogenous administration of GH and IGF-1 in the normal adult rat induces a cardiac hypertrophic response without development of significant fibrosis. Cardiac performance is increased both in vivo and in the isolated heart.
Am Heart Assoc