Its beneficial effects might be related to the prompt replenishment of reduced glutathione, scavenging tissue hydrogen peroxide and decreasing lipid hydroperoxides. However, the cardioprotective effect of NAC needs to be further studied at a later stage after resuscitation since the asphyxiating event also has prolonged effects on cardiac function. Abnormal electrocardiography, poor left ventricular function, elevated plasma concentrations of creatinine kinase and cardiac troponins have been observed in asphyxiated neonates at 24–72 h after birth. Similarly, plasma troponin I of neonates with cardiac dysfunction remains elevated at more than 72 h after birth. Taken together, these results indicate that cardiac dysfunction of asphyxiated neonates persists more than 24 h after I–R or H–R insults. Although NAC has been shown to have prolonged cardiac protective effect in various adult animal models, limited studies have been carried out to examine its prolonged effect in neonates whose anti-oxidant system is compromised especially with asphyxia. Using a surviving swine model of neonatal asphyxia. We hypothesized that the postresuscitation administration of NAC in asphyxiated newborn piglets would improve the systemic haemodynamics and oxygen transport with the attenuation of oxidative stress in the myocardium. We hereby observed that post-resuscitation NAC infusion significantly improved the overall cardiac performance, particularly at the early phase of reoxygenation, consequently normalized the systemic oxygen delivery of H2R newborn piglets throughout reoxygenation. NAC treatments also attenuated myocardial LPO accumulation, caspase-3 activity as well as lactate content, and reduced the plasma cTnI concentration by the end of reoxygenation period. The cardiac dysfunction after resuscitation contributes to the mortality and morbidity of neonates with perinatal asphyxia. Depending on the diagnostic criteria, cardiac dysfunction was observed in 29267% of asphyxiated neonates. Cardiac function can remain diminished with poor cardiac output and hypotension in the first 24248 h after birth, similar to what we observed in our model of neonatal asphyxia. Using state-of-theart technique such as functional echocardiography to determine cardiac function will be extremely revealing and useful. Nonetheless, as the result of poor systemic perfusion or delayed recovery from GSK1363089 asphyxia, about 60% these cases were associated with adverse neurological outcome. Thus, maintaining cardiac function after resuscitation may help to minimize further injury to asphyxiated neonates. As indicated by the lower CI and overall oxygen delivery, cardiac dysfunction did occur in H2R controls during reoxygenation. In contrast to the cardiac dysfunction observed in H2R controls, treating the piglets with NAC significantly improved both the CI and overall oxygen delivery during the 48 h recovery.