N-Acetylcysteine Improves the Hemodynamics and Oxidative Stress in Hypoxic Newborn Pigs Reoxygenated With 100% Oxygen

Abstract

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.

Effects of Postresuscitation N-Acetylcysteine on Cerebral Free Radical Production and Perfusion During Reoxygenation of Hypoxic Newborn Piglets

“…The F i O 2 was adjusted as tolerated by the piglets to obtain severe hypoxemia (PaO 2 of 25-35 mm Hg) for 2 h. To maintain normocapnia, the ventilator rate was adjusted to 12-20 breaths/min. After hypoxia, the piglets were resuscitated with a F i O 2 of 1.0 for 1 h, followed by 0.21 for another 3 h. This protocol of hypoxia and reoxygenation was close to but not equal to clinical practice (4,11). Five minutes after reoxygenation, piglets received either normal saline (H-R control) or NAC (30 mg/kg bolus and 20 mg/kg/h, i.v.)…”

“…The animal preparation was similar to that described previously (4,11). Briefly, anesthesia was initially maintained with inhaled isoflurane.…”

Impact of N-Acetylcysteine on Neonatal Cardiomyocyte Ischemia-Reperfusion Injury

“…Clinically, NAC is indicated for the treatment of acetaminophen overdose, for the prevention of radiocontrastinduced nephropathy, and as an adjuvant in respiratory conditions with excessive and/or thick mucus production. However, there are contradictory reports on the effects of NAC in clinical (13,14) and animal studies (15)(16)(17) of myocardial IR injury. Furthermore, there are limited data specifically focused on NAC use during infancy.…”

Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

“…20 For ROS scavenging, the superoxide dismutasemimetic Tempol (30 mg/kg IV), in combination with N-acetyl-cysteine (150 mg/kg IV), and N-mercaptoproprionylglycine (1 mg/kg/min IV) were infused in 10 minutes before the measurements. [21][22][23][24] …”