Long-term effects of growth hormone on infarct size and left ventricular function in sheep with coronary artery occlusion.
The effects of growth hormone (GH) on infarct size and left ventricular (LV) function in experimental acute myocardial infarction (AMI) have been controversial. Moreover, little, if any, information exists regarding long-term evaluation of therapeutic doses of GH in large mammalian models of AMI. We therefore aimed to assess the effect of therapeutic doses of GH over 3.5 months on infarct size and heart function in sheep with AMI. After coronary artery ligation, sheep received subcutaneous human GH 8 IU/d (n = 8) or vehicle (n = 8) over 100 days. Infarct area was similar in GH (16.9% +/- 3% of LV area) and placebo (16.5% +/- 3.7%, P = not significant) sheep. At 3 days of treatment onset, but not at later times, GH sheep had higher LV shortening fraction (30.7% +/- 3.5% vs. 24.8% +/- 6.1%, P < 0.04), systolic anterior wall thickness (10.1 +/- 0.8 vs. 8.6 +/- 1.2 mm, P < 0.02), and cardiac index (3.8 +/- 0.6 vs. 2.8 +/- 0.7 L x min x m, P < 0.01). This evolution of function parameters paralleled that of serum insulin-like growth factor 1 levels, which differed significantly only during the first week, suggesting a direct effect of GH on LV contractility. These results may suggest the usefulness of therapeutic doses of GH at the early phases of AMI but do not support maintaining the treatment for longer time.
Olea
Fernanda D
FD
Department of Physiology, Favaloro University, Buenos Aires, Argentina.
De Lorenzi
Andrea
A
Cortés
Claudia
C
Cabeza Meckert
Patricia
P
Cendoya
Oscar
O
Barra
Juan G
JG
Bercovich
Andrés
A
González
Eliseo
E
Laguens
Rubén
R
Crottogini
Alberto
A
D000818:Animals; D054059:Coronary Occlusion / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D012756:Sheep; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I