Neonatal
asphyxia may lead to cardiac and renal complications perhaps mediated by
oxygen free radicals. Using a model of neonatal
hypoxia-reoxygenation, we tested the hypothesis that
N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of pulmonary and renal artery flow (cardiac index [CI] and renal artery flow index [RAFI], respectively) and mean blood pressure. Alveolar
hypoxia was induced for 2 h, followed by
resuscitation with 100%
oxygen for 1 h and 21%
oxygen for 3 h. Animals were randomized to
sham-operated, hypoxic control, and NAC treatment (i.v. bolus of 150 mg/kg given
at 10 min of reoxygenation followed by 100 mg/kg per h infusion) groups. Myocardial and renal tissue
glutathione content and
lipid hydroperoxide levels were assayed, and histology was examined. After 2 h of
hypoxia, all animals were acidotic (pH 6.96 +/- 0.04) and in
cardiogenic shock with depressed renal blood flow. Upon reoxygenation, CI and RAFI increased but gradually deteriorated later. The NAC treatment prevented the decreased CI, stroke volume, mean blood pressure, systemic
oxygen delivery, RAFI, and renal
oxygen delivery at 2 to 4 h of reoxygenation observed in hypoxic controls (versus shams, all P < 0.05). The myocardial and renal tissue
glutathione content was significantly higher in the NAC treatment group (versus controls). The CI and RAFI at 4 h of reoxygenation correlated with the tissue
glutathione redox ratio (r = 0.5 and 0.6, respectively, P < 0.05). There were no significant differences in heart rate, pulmonary artery pressure, systemic
oxygen uptake, and tissue
lipid hydroperoxide levels between groups. No histologic injury was found in the heart or kidney. In this porcine model of neonatal
hypoxia and 100% reoxygenation, NAC improved cardiac function and renal perfusion, with improved tissue
glutathione content.