DIFFERENTIAL CARDIAC EFFECTS OF GROWTH-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I IN THE RAT - A COMBINED IN-VIVO AND IN-VITRO EVALUATION

Background Despite their increasing clinical use and recent evidence t hat growth hormone (GH) and insulin-like growth factor-1 (IGF-1) targe t the heart, there has been no systematic investigation of the effects of GK and IGF-1 on the cardiovascular system. Methods and Results Six ty normal but growing adult female rats were randomized to receive 4 w eeks 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 echoca rdiograms were performed at baseline and at 2 weeks and 4 weeks of tre atment. After the final echocardiography, rats underwent either closed -chest left ventricular (LV) catheterization or Langendorff perfusion studies. Myocyte diameter and interstitial tissue fraction were assess ed by morphometric histology. Echocardiographic and ex vivo data demon strated a LV hypertrophic response in all three groups of treated anim als that was most marked in the GH group, which alone exhibited a conc entric 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 signifi cantly higher and total systemic vascular resistance was lower in all groups of treated animals than in control animals (both P<.001), where as arterial blood pressure did not differ significantly. All indexes o f in vivo and in vitro cardiac function were higher in GH- and IGF-1-t reated rats than in control animals, whereas combination therapy yield ed a blunted effect. Myocyte diameter was increased in all three treat ed groups without an increase in interstitial tissue. Conclusions Exog enous administration of GH and IGF-1 in the normal adult rat induces a cardiac hypertrophic response without development of significant fibr osis. Cardiac performance is increased both in vivo and in the isolate d heart.