Article Text

SYSTEMIC AND PULMONARY HEMODYNAMIC RECOVERY OF ASPHYXIATED NEWBORN PIGLETS AFTER POST-RESUSCITATION TREATMENT WITH N-ACETYLCYSTEINE AND A NITRIC OXIDE SYNTHASE INHIBITOR
  1. T F Lee1,
  2. C N Tymafichuk1,
  3. P-Y Cheung1,2
  1. 1Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
  2. 2Department of Pharmacology, University of Alberta, Edmonton, AB, Canada

Abstract

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.

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