Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts

Background. Severe myocardial hypertrophy is associated with decreased tole rance to ischemia compared with normal hearts. We hypothesized that treatme nt with insulin-like growth factor-1 (IGF-1) improves postischemic myocardi al recovery by increasing glucose uptake during ischemia. and early reperfu sion. Methods. Banding of the thoracic aorta in 10-day-old rabbits created pressu re-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic ban ded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia. with or without IGF-1 in the preischemic perfusate and cardiopleg ia. followed by 30 minutes of reperfusion. Results. 2-Deoxyglucose uptake (P-31-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. I nsulin-like growth factor-1 restored glucose uptake and PI-3-kinase activit y to control levels in the hypertrophied hearts and both effects were block ed 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 tol erance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are li kely mediated through a PI-3-kinase-dependent pathway. (C) 2001 by The Soci ety of Thoracic Surgeons.