| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
From the *Department of Anesthesiology, The Medical College of Wisconsin and the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin; Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin; and Departments of Medicine (Division of Cardiovascular Diseases) and Pharmacology and Toxicology, The Medical College of Wisconsin and the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin.
Address correspondence and reprint requests to Paul S. Pagel, MD, PhD, Clement J. Zablocki Veterans Affairs Medical Center, 5000 W. National Avenue, Milwaukee, WI 53295. Address e-mail to pspagel{at}mcw.edu.
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.
This article has been cited by other articles:
|
|
 |
|
  P. S. Pagel, J. G. Krolikowski, P. F. Pratt Jr, Y. H. Shim, J. Amour, D. C. Warltier, and D. Weihrauch The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits Anesth. Analg., September 1, 2008; 107(3): 762 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Pagel, J. G. Krolikowski, P. F. Pratt Jr, Y. H. Shim, J. Amour, D. C. Warltier, and D. Weihrauch Inhibition of Glycogen Synthase Kinase or the Apoptotic Protein p53 Lowers the Threshold of Helium Cardioprotection In Vivo: The Role of Mitochondrial Permeability Transition Anesth. Analg., September 1, 2008; 107(3): 769 - 775. [Abstract] [Full Text] [PDF]
|
|
|
