The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits. Anesth Analg 2008 Sep;107(3):762-8
Date
08/21/2008Pubmed ID
18713880Pubmed Central ID
PMC2569865DOI
10.1213/ane.0b013e3181815995Scopus ID
2-s2.0-51449099643 (requires institutional sign-in at Scopus site) 32 CitationsAbstract
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.
Author List
Pagel PS, Krolikowski JG, Pratt PF Jr, Shim YH, Amour J, Warltier DC, Weihrauch DAuthor
Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiotonic Agents
Enzyme Inhibitors
Fluorescein
Helium
Hemodynamics
Indazoles
Indicators and Reagents
Ischemic Preconditioning, Myocardial
Male
Microscopy, Confocal
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase Type III
Rabbits
