Reactive oxygen species and mitochondrial adenosine triphosphate-regulated potassium channels mediate helium-induced preconditioning against myocardial infarction in vivo.
OBJECTIVE
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.


METHODS
A randomized, prospective study.


METHODS
A university research laboratory.


METHODS
Male New Zealand white rabbits.


METHODS
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.


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.
Pagel
Paul S
PS
Department of Anesthesiology, Medical College of Wisconsin and Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. pspagel@mcw.edu
Krolikowski
John G
JG
Pratt
Phillip F
PF
Shim
Yon Hee
YH
Amour
Julien
J
Warltier
David C
DC
Weihrauch
Dorothee
D
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D006371:Helium / Q000494:pharmacology / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control*; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*
D015221:Potassium Channels; D017382:Reactive Oxygen Species; D006371:Helium; D000255:Adenosine Triphosphate