Bcl-2 family proteins play a crucial role in the cytoprotective action of insulin-like growth factor-I (IGF-I) by regulating cell death signaling at the mitochondrial level. The present study examined the effect of IGF-I on the expression of Bcl-2 family proteins in the rat heart mitochondria in relation to myocardial protection against ischemia-reperfusion injury. Systemic IGF-I (1 mg) treatment in the rat increased Bcl-xL and attenuated Bax 12-24 h later in the heart mitochondria fraction. Permeability transition and cytochrome c release occurred in a Ca(2+) concentration-dependent manner in the vehicle-treated mitochondria. This was significantly inhibited by the IGF-I-pretreatment. Moreover, ATP synthesis was significantly greater in the IGF-I-pretreated mitochondria. IGF-I pretreatment 24 h before 25 min of global ischemia in the isolated rat heart model significantly improved recovery of isovolumic left ventricular function and inhibited creatine kinase release during reperfusion. This was associated with a significantly less number of terminal transferase labeling-positive myocytes and nonmyocytes 2 h after reperfusion. These results suggest that IGF-1 differentially regulates Bcl-xL and Bax in heart mitochondria, which may be causally related to myocardial protection against ischemia-reperfusion injury.

These results suggest that myocardial protection by low-grade ischemic preconditioning and potassium cardioplegia are mediated through enhanced translocation of protein kinase C alpha to the membrane. It is therefore suggested that activation of the novel protein kinase C isoforms is necessary to potentiate myocardial protection under potassium cardioplegia.

These results suggest that insulin-like growth factor 1, but not insulin with a conventional dose, protects motor neuron cells from ischemic spinal cord injury associated with differential regulation of Bcl-xL and Bax protein.

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.

Treatment for postinfarction ventricular septal defect has been improving for several decades. Aggressive resection of the infarcted myocardium (infarctectomy and closure technique) and preserving infarcted myocardium (infarct exclusion technique) have been technically modified. Recent improvement includes use of surgical glue, using an additional patch for infarct exclusion, septal exclusion, sandwich technique via right or left ventricular approach, and endovascular repair. This field still has room for cardiac surgeons to improve surgical strategy and technique.