HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/H1296    most recent 01282.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lu, X. Articles by Schaefer, S. Search for Related Content PubMed PubMed Citation Articles by Lu, X. Articles by Schaefer, S.

Activation of NF-B is a critical element in the antiapoptotic effect of anesthetic preconditioning

Departments of ¹Internal Medicine, Division of Cardiovascular Medicine, and ²Anesthesiology and Pain Management, University of California, Davis; and ³Cardiology Section, Department of Veteran Affairs, Northern California Health Care System, Mather, California; and ⁴Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada

Submitted 11 December 2008 ; accepted in final form 19 March 2009

Anesthetic preconditioning (APC), defined as brief exposure to inhalational anesthetics before cardiac ischemia-reperfusion (I/R), limits injury in both animal models and in humans. APC can result in the production of reactive oxygen species (ROS), and prior work has shown that APC can modify activation of NF-B during I/R, with consequent reduction in the expression of inflammatory mediators. However, the role of NF-B activation before I/R is unknown. Therefore, these experiments tested the hypothesis that APC-induced ROS results in activation of NF-B before I/R, with consequent increased expression of antiapoptotic proteins such as Bcl-2 and decreased apoptosis. Experiments utilized an established perfused heart rat model of sevoflurane APC and I/R. The role of NF-B was defined by a novel method of transient inhibition of the regulatory kinase IKK using the reversible inhibitor SC-514. In addition to functional measures of left ventricular developed and end-diastolic pressure, phosphorylation of IB and activation of NF-B were measured along with cytosolic protein content of Bcl-2, release of cytochrome c, and degradation of caspase-3. APC resulted in ROS-dependent phosphorylation of IB and activation of NF-B before I/R. APC also increased the expression of Bcl-2 before I/R. In addition to functional protection following I/R, APC resulted in lower release of cytochrome c and caspase-3 degradation. These protective effects of APC were abolished by transient inhibition of IB phosphorylation and NF-B activation by SC-514 followed by washout. ROS-dependent activation of NF-B by APC before I/R is a critical element in the protective effect of APC. APC reduces apoptosis and functional impairment by increasing Bcl-2 expression before I/R. Interventions that increase NF-B activation before I/R should protect hearts from I/R injury.

nuclear factor-B; reactive oxygen species