(Circulation. 1996;93:800-809.)
© 1996 American Heart Association, Inc.
Articles |
Differential Cardiac Effects of Growth Hormone and Insulin-like Growth Factor1 in the Rat
A Combined In Vivo and In Vitro Evaluation
Presented in part at the 67th Scientific Session, American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form (Circulation. 1994;90[suppl I]:I-17).
From the Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Department of Medicine (Cardiovascular Division [A.C., H.S., S.E.K., J.P.M., P.S.D.] and Endocrinology [A.C.M.]), Beth Israel Hospital and Harvard Medical School, Boston, Mass; and Genentech Inc (R.C.), South San Francisco, Calif.
Correspondence to Pamela S. Douglas, MD, Cardiovascular Division, Beth Israel Hospital, 330 Brookline Ave, Boston, MA 02215. E-mail pdouglas@bih.harvard.edu.
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.
Key Words: growth factors • ventricular hypertrophy • cardiac function
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