Cardiovascular effects of insulin-like growth factor-1 and growth hormone in chronic left ventricular failure in the rat.
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.


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/dt(max) 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 cardia index (P < .035) in rats with a large myocardial infarction.
Duerr
R L
RL
Department of Medicine, University of California at San Diego 92093-0613, USA.
McKirnan
M D
MD
Gim
R D
RD
Clark
R G
RG
Chien
K R
KR
Ross
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D017023:Coronary Angiography; D003971:Diastole; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone