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Reactive Oxygen Species and Mitochondrial Adenosine Triphosphate-Regulated Potassium Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo

Authors
 Paul S. Pagel  ;  John G. Krolikowski  ;  Phillip F. Pratt Jr  ;  Yon Hee Shim  ;  Julien Amour  ;  David C. Warltier  ;  Dorothee Weihrauch 
Citation
 JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA, Vol.22(4) : 554-559, 2008 
Journal Title
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
ISSN
 1053-0770 
Issue Date
2008
MeSH
Adenosine Triphosphate/physiology* ; Animals ; Helium/pharmacology ; Helium/therapeutic use* ; Ischemic Preconditioning, Myocardial/methods* ; Male ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/physiology ; Myocardial Infarction/metabolism ; Myocardial Infarction/prevention & control* ; Potassium Channels/physiology* ; Rabbits ; Reactive Oxygen Species/metabolism*
Keywords
myocardial ischemia ; preconditioning ; helium ; reactive oxygen species ; mitochondrial adenosine triphosphate–regulated potassium channels
Abstract
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.
Files in This Item:
T200805212.pdf Download
DOI
10.1053/j.jvca.2008.04.005
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Shim, Yon Hee(심연희) ORCID logo https://orcid.org/0000-0003-1921-3391
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108350
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