Faculty Collaboration Database

Sevoflurane exposure generates superoxide but leads to decreased superoxide during ischemia and reperfusion in isolated hearts. Anesth Analg 2003 Apr;96(4):949-955

Date

03/26/2003

Pubmed ID

12651639

DOI

10.1213/01.ANE.0000052515.25465.35

Scopus ID

2-s2.0-0037379380 (requires institutional sign-in at Scopus site)   116 Citations

Abstract

UNLABELLED: Reactive oxygen species (ROS) are largely responsible for cardiac injury consequent to ischemia and reperfusion, but, paradoxically, there is evidence suggesting that anesthetics induce preconditioning (APC) by generating ROS. We hypothesized that sevoflurane generates the ROS superoxide (O(2)(.-)), that APC attenuates O(2)(.-) formation during ischemia, and that this attenuation is reversed by bracketing APC with the O(2)(.-) scavenger manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the putative mitochondrial adenosine triphosphate-sensitive potassium (mK(ATP)) channel blocker 5-hydroxydecanoate (5-HD). O(2)(.-) was measured continuously in guinea pig hearts by using dihydroethidium. Sevoflurane was administered alone (APC), with MnTBAP, or with 5-HD before 30 min of ischemia and 120 min of reperfusion. Control hearts underwent no pretreatment. Sevoflurane directly increased O(2)(.-); this was blocked by MnTBAP but not by 5-HD. O(2)(.-) increased during ischemia and during reperfusion. These increases in O(2)(.-) were attenuated in the APC group, but this was prevented by MnTBAP or 5-HD. We conclude that sevoflurane directly induces O(2)(.-) formation but that O(2)(.-) formation is decreased during subsequent ischemia and reperfusion. The former effect appears independent of mK(ATP) channels, but not the latter. Our study indicates that APC is initiated by ROS that in turn cause mK(ATP) channel opening. Although there appears to be a paradoxical role for ROS in triggering and mediating APC, a possible mechanism is offered.

IMPLICATIONS: Reactive oxygen species (ROS) are implicated in triggering anesthetic preconditioning (APC). The ROS superoxide (O(2)(.-)) was measured continuously in guinea pig isolated hearts. Sevoflurane directly increased O(2)(.-) but led to attenuated O(2)(.-) formation during ischemia. This demonstrates triggering of APC by ROS and clarifies the mechanism of cardioprotection during ischemia.

Author List

Kevin LG, Novalija E, Riess ML, Camara AKS, Rhodes SS, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David F. Stowe PhD, MA, MA Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

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

ATP-Binding Cassette Transporters
Anesthetics, Inhalation
Animals
Blood Pressure
Calcium
Coronary Circulation
Electron Transport
Ethidium
Fluorescent Dyes
Free Radical Scavengers
Guinea Pigs
Heart Ventricles
In Vitro Techniques
Ischemic Preconditioning, Myocardial
KATP Channels
Methyl Ethers
Myocardial Reperfusion Injury
Oxidants
Potassium Channel Blockers
Potassium Channels
Potassium Channels, Inwardly Rectifying
Reactive Oxygen Species
Spectrometry, Fluorescence
Superoxides
Ventricular Function, Left