Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism.
Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term positive inotropic effect (PIE) in the myocardium under nonischemic conditions. IGF-I also conferred cytoprotection against ischemia and reperfusion injury in various organs. IGF-I may, therefore, facilitate the recovery of postischemic cardiac function. Isolated and crystalloid-perfused rat heart was subjected to 25 min of normothermic ischemia followed by 30 min of reperfusion. IGF-I produced PIE in a dose-dependent manner at concentrations ranging between 1 and 100 nM under nonischemic conditions. Although 1 nM isoproterenol produced much greater PIE and myocardial energy conversion efficiency (MECE) than did 65 nM IGF-I in this condition, the same concentration of IGF-I administered during reperfusion conferred better recovery of left ventricular function and MECE compared with isoproterenol. The improved cardiac performance by IGF-I was associated with lower release of creatine kinase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile function and inhibition of CK release in the postischemic heart. We conclude that IGF-I administered during reperfusion accelerates recovery of cardiac performance and mitigates myocardial injury through a wortmannin-sensitive mechanism.
Otani
H
H
Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Moriguchi, Osaka, Japan. otanih@takii.kmu.ac.jp
Yamamura
T
T
Nakao
Y
Y
Hattori
R
R
Kawaguchi
H
H
Osako
M
M
Imamura
H
H
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D003402:Creatine Kinase; D007545:Isoproterenol; D000077191:Wortmannin