title: Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: Friehs
authors.forename: C
authors.initials: C
authors.lastname: Stamm
authors.forename: H
authors.initials: H
authors.lastname: Cao-Danh
authors.forename: F X
authors.initials: FX
authors.lastname: McGowan
authors.forename: P J
authors.initials: PJ
authors.lastname: del Nido
mesh_terms: 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
chemical_list: D007334:Insulin-Like Growth Factor I; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases