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Impact of N-acetylcysteine on Neonatal Cardiomyocyte Ischemia-Reperfusion Injury.
MedLine Citation:
PMID:  21427628     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Reactive oxygen species (ROS) are hypothesized to play a key role in myocardial ischemia-reperfusion (IR) injury after cardiopulmonary bypass in children. Clinical studies in adults and several animal models suggest that myocardial IR injury involves cardiomyocyte apoptosis and necrosis. This study investigated a potential relationship between IR-induced ROS production and neonatal cardiomyocyte apoptosis using both in-vitro and ex-vivo techniques. For in-vitro experiments, embryonic rat cardiomyocytes (H9c2 cells) exposed to hypoxia-reoxygenation (HR) showed a time-dependent increase in gp91 (a marker for ROS production by NADPH oxidases), caspase-3 (a key mediator of apoptosis) expression and a decrease in the glutathione redox ratio. N-acetylcysteine (NAC; 0.25-2 mM), a potent antioxidant, decreased gp91 and caspase-3 expression, inhibited apoptosis, and restored the glutathione redox ratio. For ex-vivo study, IR injury significantly reduced left ventricular (LV) function and increased the expression of gp91 and caspase-3 in Langendorff-perfused neonatal (7-14 days) rabbit hearts. NAC (0.4 mM) treatment completely attenuated LV dysfunction after IR. In summary, neonatal myocardial IR injury is associated with an increase in cardiomyocyte oxidative stress and apoptosis. NAC attenuates apoptosis in an in-vitro embryonic rat cardiomyocyte model of HR, and myocardial dysfunction in an ex-vivo neonatal rabbit model of myocardial IR injury. ABBREVIATIONS::
Authors:
Yun-Wen Peng; Carolyn L Buller; John R Charpie
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-21
Journal Detail:
Title:  Pediatric research     Volume:  -     ISSN:  1530-0447     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pediatrics & Communicable Diseases, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109.
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