Similarly to those reported in adult patients with myocardial ischemia, the LY2109761 plasma cTnI level of H2R controls peaked at 12 h after hypoxia and maintained high during the reoxygenation period. NAC treatment significantly decreased H2R-induced elevated cTnI concentration at the end of experimental period, indicating attenuated myocardial injury. Of note, this was associated with the significant reduction in myocardial lactate content, which was negatively correlated with CI. Interestingly, Harrison et al suggested that the increase in oxygen delivery could account for the beneficial effect of NAC in patients with fulminant hepatic failure. Taken together, our results demonstrated that NAC could elicit a prolonged improvement in cardiac recovery in newborn asphyxiated piglets. NAC is a precursor of L-cysteine and reduced glutathione. It releases thione and converts glutathione into reduced form of GSH which is exhausted during hypoxia and ischemia. Similarly to that reported previously in our acute study, a significant increase in myocardial GSH, but not GSSG and redox ratio, was observed in piglets receiving NAC treatment. Although the myocardial contents and redox ratio of glutathione were similar in H2R control and sham-operated group at the end of the experiment, the apparent contradiction could be due the fact that the endogenous glutathione system may have been restored during the prolonged recovery period. Furthermore, in addition to direct conversion from NAC, the increase in GSH in NAC-treated piglets may also be due to increased GSSHreductase activity. Interestingly, oxidative stress has been shown to stimulate pentose-phosphate pathway that generates NADPH, a necessary cofactor for GSSH-reductase to maintain cellular GSH. As it has been shown previously that myocardial injury can be minimized by enhancing the glutathione content, we speculate that replenishing endogenous GSH may, at least in part, account for the beneficial effect of NAC in improving cardiac recovery. Associated with the impaired cardiac function, increases in myocardial LPO and caspase-3 were observed in H2R controls. Interestingly, the negative correlation between CI with both LPO accumulation and caspase-3 activity in the left ventricle may reflect the involvement of ROS in its pathogenesis. Indeed, the correlation between oxygen concentrations used in neonatal resuscitation and myocardial injury has been demonstrated. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins and cause apoptosis cascades, all potentially damaging to normal cellular function. Complementary to our findings, reduced cardiac function has been observed in hearts perfused with various ROS generating systems. Therefore, these findings indicate that cardiac dysfunction in hypoxic newborn piglets observed after reoxygenation is associated with ROS-induced oxidative stress. Treating H2R piglets with NAC significantly attenuated the increased accumulation.