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

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. (C) 2008 Elsevier Inc. All rights reserved.