The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits

Anesth Analg. 2008 Sep;107(3):762-8. doi: 10.1213/ane.0b013e3181815995.

Abstract

Background: Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo.

Methods: Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment.

Results: Helium reduced (P < 0.05) infarct size (24% +/- 4% of the left ventricular area at risk; mean +/- sd) compared with control (46% +/- 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 +/- 8 vs 15 +/- 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence.

Conclusions: The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Fluorescein / pharmacology
  • Helium / pharmacology*
  • Hemodynamics
  • Indazoles / pharmacology
  • Indicators and Reagents / pharmacology
  • Ischemic Preconditioning, Myocardial*
  • Male
  • Microscopy, Confocal / methods
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / metabolism*
  • Rabbits

Substances

  • 4,5-diaminofluorescein diacetate
  • Cardiotonic Agents
  • Enzyme Inhibitors
  • Indazoles
  • Indicators and Reagents
  • Helium
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Fluorescein
  • 7-nitroindazole
  • NG-Nitroarginine Methyl Ester