Previous data have shown that enhanced Akt signaling inhibits cardiac myocyte apoptosisin vitro and in vivo. To elucidate the contribution of apoptosis to the pathogenesis of the infarct, we investigated whether intra-coronary Akt gene delivery could reduce gross infarct size following ischemia/reperfusion injury.

Replication-defective adenoviral constructs encoding a myristoylated, constitutively-active form of Akt (myrAkt) or β -galactosidase were delivered to rat hearts by intracoronary perfusion. Twenty-four h after gene transduction, hearts in both groups underwent 45 min of ischemia followed by 4 h of reperfusion. A third group of animals also underwent ischemia–reperfusion injury but were not transduced with an adenoviral vector. The proportion of the left ventricle at risk was not different among the experimental groups. However, infarct size as a proportion of the area at risk was significantly lower in myrAkt-treated group than in the β -galactosidase treated group or in the control group that was not subject to intracoronary perfusion (myrAkt=20.9±2.7%v β -galactosidase=56.1±3.9% and control=46.2±4.6%, P<0.05), as was infarct size as a proportion of the total left ventricle (myrAkt=11.4±3.2 v β -galactosidase=32.9±3.3 and control=23.5±3.0, P<0.05).

These data demonstrate that Akt signaling limits infarct size following ischemia/reperfusion injury and they indicate that the activation of this pathway may be useful in protecting against myocardial loss in the diseased heart.