Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts.
BACKGROUND
Severe myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion.


METHODS
Banding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion.


RESULTS
2-Deoxyglucose uptake (31P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts.


CONCLUSIONS
These data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.
Friehs
I
I
Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stamm
C
C
Cao-Danh
H
H
McGowan
F X
FX
del Nido
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003326:Coronary Circulation; D003847:Deoxyglucose / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011817:Rabbits
D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases