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 (KATP) channels in this process are unknown. The authors tested the hypothesis that ROS and mitochondrial KATP 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 KATP 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 KATP channels mediate helium-induced preconditioning in vivo.