JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Venkatapuram, S.
Right arrow Articles by Pagel, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Venkatapuram, S.
Right arrow Articles by Pagel, P. S.
Related Collections
Right arrow Cardiovascular
Right arrow Resuscitation
Right arrow Pharmacology

Anesth Analg 2006;103:1400-1405
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000240903.63832.d8e

CARDIOVASCULAR ANESTHESIA

Inhibition of Apoptotic Protein p53 Lowers the Threshold of Isoflurane-Induced Cardioprotection During Early Reperfusion in Rabbits

Suneetha Venkatapuram, MD{ddagger}, Chen Wang, MD*, John G. Krolikowski, BA*, Dorothee Weihrauch, DVM, PhD*, Judy R. Kersten, MD*{dagger}, David C. Warltier, MD, PhD*{dagger}{ddagger}§, Phillip F. Pratt, Jr, PhD*{dagger}, and Paul S. Pagel, MD, PhD*§

From the *Departments of Anesthesiology, {dagger}Pharmacology and Toxicology, and {ddagger}Medicine (Division of Cardiovascular Diseases), Medical College of Wisconsin and The Clement J. Zablocki Veterans Affairs Medical Center; and §Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin.

Address correspondence and reprint requests to Paul S. Pagel, MD, PhD, Medical College of Wisconsin, MEB-M4280, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226. Address e-mail to pspagel{at}mcw.edu.

INTRODUCTION: Exposure to isoflurane before and during early reperfusion protects against myocardial infarction by activating phosphatidylinositol-3-kinase (PI3K)-mediated signaling. The apoptotic protein, p53, is regulated by PI3K, and inhibition of p53 protects against ischemic injury. We tested the hypothesis that p53 inhibition lowers the threshold of isoflurane-induced postconditioning in vivo.

METHODS: Rabbits (n = 73) instrumented for hemodynamic measurement and subjected to a 30-min left anterior descending coronary artery occlusion and 3-h reperfusion received 0.9% saline (control), isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) administered for 3 min before and 2 min after reperfusion, the p53 inhibitor pifithrin-{alpha} (1.5 or 3.0 mg/kg), or 0.5 MAC isoflurane plus 1.5 mg/kg pifithrin-{alpha}. Other rabbits received 3.0 mg/kg pifithrin-{alpha} or 0.5 MAC isoflurane plus 1.5 mg/kg pifithrin-{alpha} after pretreatment with the selective PI3K inhibitor wortmannin (0.6 mg/kg) or the mitochondrial permeability transition pore opener atractyloside (5 mg/kg).

RESULTS: Isoflurane (1.0 but not 0.5 MAC), pifithrin-{alpha} (3.0 but not 1.5 mg/kg), and the combination of 0.5 MAC isoflurane plus 1.5 mg/kg pifithrin-{alpha} significantly (P < 0.05) reduced infarct size (21% ± 4%, 43% ± 7%, 22% ± 4%, 45% ± 4%, and 28% ± 3% [mean ± sd], respectively, of left ventricular area at risk; triphenyltetrazolium chloride staining) when compared with control (45% ± 2%). Atractyloside, but not wortmannin, abolished 3.0 mg/kg pifithrin-{alpha}-induced cardioprotection, whereas atractyloside and wortmannin blocked reductions in infarct size produced by 0.5 MAC isoflurane plus 1.5 mg/kg pifithrin-{alpha}.

CONCLUSION: The results indicate that inhibition of the apoptotic protein p53 lowers the threshold of isoflurane-induced cardioprotection during early reperfusion in vivo.




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
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]


Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.