CARDIOVASCULAR EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-HORMONE IN CHRONIC LEFT-VENTRICULAR FAILURE IN THE RAT

Background Insulin-like growth factor-1 (IGF-1) appears to have favora ble 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 bene ficial 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 horm one (0.1 mg BID) or to placebo for 4 weeks. Treated rats had significa nt increases in body weight (22%), while the ratio of heart weight to body weight was unchanged. Under anesthesia, cardiac output (fluoresce nt microspheres) increased 46%, and systemic vascular resistance decre ased by 21% (P<.001) in the treated group; a significant (22%) increas e of the cardiac index was limited to treated rats with large myocardi al infarctions. Small increases in the reduced left ventricular ejecti on fractions and left ventricular dP/dt(max) values with treatment wer e 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 i n the treated group. Conclusions IGF-I plus growth hormone administere d to rats with left ventricular failure starting 1 month after MI was associated with substantial body growth, decreased systemic vascular r esistance, and increased cardiac output. The failing heart also underw ent treatment-induced increases in left and right ventricular weights in proportion to body growth, but left ventricular remodeling was mino r, and a decrease in the ratio of left ventricular end-diastolic volum e to body weight reflected relatively less chamber dilation compared w ith 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.