Document Detail

Reactive oxygen species and mitochondrial adenosine triphosphate-regulated potassium channels mediate helium-induced preconditioning against myocardial infarction in vivo.
MedLine Citation:
PMID:  18662630     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels in this process are unknown. The authors tested the hypothesis that ROS and mitochondrial K(ATP) channels mediate helium-induced preconditioning in vivo. DESIGN: A randomized, prospective study. SETTING: A university research laboratory. PARTICIPANTS: Male New Zealand white rabbits. INTERVENTIONS: Rabbits (n = 64) were instrumented for the measurement of systemic hemodynamics and subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion and 3 hours of reperfusion. In separate experimental groups, rabbits (n = 7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or 3 cycles of 70% helium-30% oxygen administered for 5 minutes interspersed with 5 minutes of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2 mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial K(ATP) antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of a Student t test. MEASUREMENTS AND MAIN RESULTS: The myocardial infarct size was determined by using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (p < 0.05) reduced infarct size (23 +/- 4% of the area at risk; mean +/- standard deviation) compared with control (46 +/- 3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49 +/- 5%, 45 +/- 6%, and 45 +/- 3%), but these drugs blocked reductions in infarct size produced by helium (45 +/- 4%, 45 +/- 2%, and 44 +/- 3%). CONCLUSIONS: The results suggest that ROS and mitochondrial K(ATP) channels mediate helium-induced preconditioning in vivo.
Paul S Pagel; John G Krolikowski; Phillip F Pratt; Yon Hee Shim; Julien Amour; David C Warltier; Dorothee Weihrauch
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-06-17
Journal Detail:
Title:  Journal of cardiothoracic and vascular anesthesia     Volume:  22     ISSN:  1532-8422     ISO Abbreviation:  J. Cardiothorac. Vasc. Anesth.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2008-12-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9110208     Medline TA:  J Cardiothorac Vasc Anesth     Country:  United States    
Other Details:
Languages:  eng     Pagination:  554-9     Citation Subset:  IM    
Department of Anesthesiology, Medical College of Wisconsin and Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA.
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MeSH Terms
Adenosine Triphosphate / physiology*
Helium / pharmacology,  therapeutic use*
Ischemic Preconditioning, Myocardial / methods*
Mitochondria, Heart / drug effects,  physiology
Myocardial Infarction / metabolism,  prevention & control*
Potassium Channels / physiology*
Reactive Oxygen Species / metabolism*
Grant Support
GM 066730/GM/NIGMS NIH HHS; HL 054820/HL/NHLBI NIH HHS; P01 GM066730-040001/GM/NIGMS NIH HHS; R01 HL054820-11/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Potassium Channels; 0/Reactive Oxygen Species; 56-65-5/Adenosine Triphosphate; 7440-59-7/Helium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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