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(Circulation. 1996;93:2188-2196.)
© 1996 American Heart Association, Inc.
Articles |
Cardiovascular Effects of Insulin-Like Growth Factor-1 and Growth Hormone in Chronic Left Ventricular Failure in the Rat
From the Division of Cardiology, Department of Medicine (R.L.D., R.D.G., K.R.C., J.R.) and Department of Pathology (M.D.M.), University of California at San Diego; and Genentech, Inc (R.G.C.), South San Francisco, Calif.
Correspondence to John Ross, Jr, MD, University of California, San Diego, Department of Medicine 0613B, 9500 Gilman Dr, La Jolla, CA 92093-0613. E-mail jross@ucsd.edu.
Background Insulin-like growth factor-1 (IGF-1) appears to have favorable cardiac effects associated with left ventricular remodeling early after myocardial infarction in the rat. The present study was designed to determine whether IGF-1 combined with growth hormone would be beneficial later as well, when infarct healing and cardiac remodeling have occurred.
Methods and Results Four weeks after coronary occlusion, 36 rats were randomized to IGF-1 (3 mg·kg-1·d-1) plus growth hormone (0.1 mg BID) or to placebo for 4 weeks. Treated rats had significant increases in body weight (22%), while the ratio of heart weight to body weight was unchanged. Under anesthesia, cardiac output (fluorescent microspheres) increased 46%, and systemic vascular resistance decreased by 21% (P<.001) in the treated group; a significant (22%) increase of the cardiac index was limited to treated rats with large myocardial infarctions. Small increases in the reduced left ventricular ejection fractions and left ventricular dP/dtmax values with treatment were not significant. Treated rats showed a borderline (16%) increase in left ventricular end-diastolic volume (angiography), whereas the ratio of left ventricular end-diastolic volume to body weight was reduced in the treated group.
Conclusions IGF-1 plus growth hormone administered to rats with left ventricular failure starting 1 month after MI was associated with substantial body growth, decreased systemic vascular resistance, and increased cardiac output. The failing heart also underwent treatment-induced increases in left and right ventricular weights in proportion to body growth, but left ventricular remodeling was minor, and a decrease in the ratio of left ventricular end-diastolic volume to body weight reflected relatively less chamber dilation compared with controls. A significant interaction between size of the myocardial infarction and treatment was observed for several variables, and IGF-1 and growth hormone increased the cardiac index (P<.035) in rats with a large myocardial infarction.
Key Words: hypertrophy • remodeling • cardiac output • growth substances • myocardial infarction
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