HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsScott T Johnson, David L Bigam, Marwan Emara, Laila Obaid, Graham Slack, Gregory Korbutt, Laurence D Jewell, John Van Aerde, Po-Yin Cheung
JournalShock (Augusta, Ga.) (Shock) Vol. 28 Issue 4 Pg. 484-90 (Oct 2007) ISSN: 1073-2322 [Print] United States
PMID17577140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lipid Peroxides
  • Glutathione
  • Oxygen
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology, therapeutic use)
  • Animals
  • Animals, Newborn
  • Blood Flow Velocity (drug effects)
  • Blood Pressure (drug effects)
  • Female
  • Glutathione (metabolism)
  • Hypoxia (drug therapy, physiopathology)
  • Kidney (blood supply, drug effects, metabolism)
  • Lipid Peroxides (metabolism)
  • Male
  • Myocardium (metabolism)
  • Oxidative Stress (drug effects)
  • Oxygen (metabolism, pharmacology, therapeutic use)
  • Oxygen Inhalation Therapy (methods)
  • Stroke Volume (drug effects)
  • Swine
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: