Objectives Reactive oxygen species (ROS) have been implicated in myocardial deficits associated with neonatal asphyxia. Significant improvement in myocardial recovery has been shown with interventions to decrease ROS after ischemia/hypoxia. We investigated whether co-administration of N-Acetylcysteine (NAC, a ROS scavenger) and NG-Monomethyl-L-Arginine (NMMA, a non-selective nitric oxide synthase inhibitor) after resuscitation can have better hemodynamic recovery.
Methods Newborn piglets (1–3 d) were anesthetized, acutely instrumented and underwent an established protocol of hypoxia–reoxygenation (H-R). They were block-randomized into a sham-operated group (without H-R, n = 5) and four H-R groups (2 h normocapnic alveolar hypoxia followed by 4 h reoxygenation, n = 8/group). At 5 min after reoxygenation, piglets were given either saline, NAC (30 mg/kg bolus + 20 mg/kg/h infusion), NMMA (0.1 mg/kg bolus + 0.1 mg/kg/h infusion) or NAC+NMMA in a blinded, randomized fashion.
Results Hypoxic piglets were acidotic and had cardiogenic shock. Both cardiac index and stroke volume remained lower than normoxic baseline values during reoxygenation. Post-resuscitation treatment with NMMA alone did not improve systemic hemodynamic recovery, but caused pulmonary hypertension. Treating H-R piglets with NAC alone or NAC+NMMA improved cardiac index and stroke volume, with no effect on heart rate and blood pressure. These treatments also decreased myocardial glutathione redox ratio, lipid hydroperoxide and nitrate/nitrite levels (vs. H-R controls). There was no significant difference between NAC alone and NAC+NMMA treatment groups in these physiological and biochemical parameters.
Conclusions Post-resuscitation NAC administration improved cardiac function and reduced myocardial oxidative stress in newborn piglets with H-R insults. Addition of NMMA did not provide any further beneficial effect.