H. Otani et al., Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a Wortmannin-sensitive mechanism, J CARDIO PH, 35(2), 2000, pp. 275-281
Citations number
24
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term
positive inotropic effect (PIE) in the myocardium under nonischemic condit
ions. 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 repe
rfusion. ICF-I produced PIE in a dose-dependent manner at concentrations ra
nging between 1 and 100 nM under nonischemic conditions. Although 1 nM isop
roterenol produced much greater PIE and myocardial energy conversion effici
ency (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 car
diac performance by IGF-I was associated with lower release of creatine kin
ase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol
kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile f
unction 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.