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306 A Novel Anti-Oxidant to Counteract Oxidative Stress During Resuscitation after Birth Asphyxia
  1. E Henckel1,
  2. R Solberg2,
  3. TE Calisch2,
  4. S Norgren3,
  5. K Bohlin1,
  6. OD Saugstad2
  1. 1Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Pediatric Research, Oslo University Hospital - Rikshospitalet, Oslo, Norway
  3. 3Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden

Abstract

Background and Aims Oxidative stress contributes to tissue damage after perinatal asphyxia. The thiol-containing free radical scavenger N-acetylcysteine amide (NACA) is a promising new anti-oxidant with good penetration into the mitochondria. The objective was to investigate the protective effect of NACA in a piglet model of birth asphyxia.

Methods Anesthetized newborn piglets (n=51) were subjected to global hypoxemia and block-randomized to either

  1. intravenous administration of NACA 300 mg/kg and resuscitated with 21% oxygen for 30 min,

  2. saline and 21% oxygen,

  3. NACA and 100% oxygen or

  4. saline and 100% oxygen.

After resuscitation, the piglets were followed for 9 hours and samples for several markers of injury and oxidative stress were collected. Reported here are clinical parameters and measurements of reduced to oxidized gluthatione (GSH/GSSG).

Results Thirty minutes after end-resuscitation metabolic acidosis was less pronounced in the 100%-NACA group compared to 100%-oxygen-alone (lactate 8.1±2.6 vs 10.9±3.4, p<0.05). This difference was not shown for the 21%-oxygen groups. Mean arterial blood pressure and hemoglobin levels remained similar between the groups. The GSSG values were generally low. At end-resuscitation GSH was lower in 100%-NACA compared to 100%-oxygen-alone group (164±111 vs 255±113 µmol, p<0.05) and delta-GSH during resuscitation greater (143±49 vs 32±66 µmol p<0.001).

Conclusions The data indicate that NACA may enhance immediate recovery, improve mithochondrial glutatione metabolism and restore the cell to a normal metabolism following asphyxia and rescucitation. Upcoming analyses of histopathology and injury markers will further elucidate neuroprotective effect of NACA treatment following birth asphyxia.

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