Faculty Collaboration Database

Noble gases without anesthetic properties protect myocardium against infarction by activating prosurvival signaling kinases and inhibiting mitochondrial permeability transition in vivo. Anesth Analg 2007 Sep;105(3):562-9

Date

08/25/2007

Pubmed ID

17717207

DOI

10.1213/01.ane.0000278083.31991.36

Scopus ID

2-s2.0-34548134885 (requires institutional sign-in at Scopus site)   106 Citations

Abstract

BACKGROUND: The anesthetic noble gas, xenon, produces cardioprotection. We hypothesized that other noble gases without anesthetic properties [helium (He), neon (Ne), argon (Ar)] also produce cardioprotection, and further hypothesized that this beneficial effect is mediated by activation of prosurvival signaling kinases [including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, and 70-kDa ribosomal protein s6 kinase] and inhibition of mitochondrial permeability transition pore (mPTP) opening in vivo.

METHODS: Rabbits (n = 98) instrumented for hemodynamic measurement and subjected to a 30-min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), three cycles of 70% He-, Ne-, or Ar-30% O2 administered for 5 min interspersed with 5 min of 70% N2-30% O2 before LAD occlusion, or three cycles of brief (5 min) ischemia interspersed with 5 min reperfusion before prolonged LAD occlusion and reperfusion (ischemic preconditioning). Additional groups of rabbits received selective inhibitors of phosphatidylinositol-3-kinase (wortmannin; 0.6 mg/kg), extracellular signal-regulated kinase (PD 098059; 2 mg/kg), or 70-kDa ribosomal protein s6 kinase (rapamycin; 0.25 mg/kg) or mPTP opener atractyloside (5 mg/kg) in the absence or presence of He pretreatment.

RESULTS: He, Ne, Ar, and ischemic preconditioning significantly (P < 0.05) reduced myocardial infarct size [23% +/- 4%, 20% +/- 3%, 22% +/- 2%, 17% +/- 3% of the left ventricular area at risk (mean +/- sd); triphenyltetrazolium chloride staining] versus control (45% +/- 5%). Wortmannin, PD 098059, rapamycin, and atractyloside alone did not affect infarct size, but these drugs abolished He-induced cardioprotection.

CONCLUSIONS: The results indicate that noble gases without anesthetic properties produce cardioprotection by activating prosurvival signaling kinases and inhibiting mPTP opening in rabbits.

Author List

Pagel PS, Krolikowski JG, Shim YH, Venkatapuram S, Kersten JR, Weihrauch D, Warltier DC, Pratt PF Jr

Author

Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Androstadienes
Animals
Argon
Atractyloside
Cardiotonic Agents
Disease Models, Animal
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases
Flavonoids
Heart Ventricles
Helium
Ischemic Preconditioning, Myocardial
Male
Mitochondria, Heart
Mitochondrial Membrane Transport Proteins
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Myocardium
Neon
Noble Gases
Phosphatidylinositol 3-Kinases
Protein Kinase Inhibitors
Protein Kinases
Rabbits
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction
Sirolimus