Faculty Collaboration Database

Anesthetic preconditioning: the role of free radicals in sevoflurane-induced attenuation of mitochondrial electron transport in Guinea pig isolated hearts. Anesth Analg 2005 Jan;100(1):46-53

Date

12/24/2004

Pubmed ID

15616050

DOI

10.1213/01.ANE.0000139346.76784.72

Scopus ID

2-s2.0-10944258443 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

Cardioprotection by anesthetic preconditioning (APC) can be abolished by nitric oxide (NO*) synthase inhibitors or by reactive oxygen species (ROS) scavengers. We previously reported attenuated mitochondrial electron transport (ET) and increased ROS generation during preconditioning sevoflurane exposure as part of the triggering mechanism of APC. We hypothesized that NO* and other ROS mediate anesthetic-induced ET attenuation. Cardiac function and reduced nicotinamide adenine dinucleotide (NADH) fluorescence, an index of mitochondrial ET, were measured online in 68 Langendorff-prepared guinea pig hearts. Hearts underwent 30 min of global ischemia and 120 min of reperfusion. Before ischemia, hearts were temporarily perfused with superoxide dismutase, catalase, and glutathione to scavenge ROS or N(G)-nitro-L-arginine-methyl-ester (L-NAME) to inhibit NO* synthase in the presence or absence of 1.3 mM sevoflurane (APC). APC temporarily increased NADH before ischemia, i.e., it attenuated mitochondrial ET. Both this NADH increase and the cardioprotection by APC on reperfusion were prevented by superoxide dismutase, catalase, and glutathione and by N(G)-nitro-L-arginine-methyl-ester. Thus, ROS and NO*, or reaction products including peroxynitrite, mediate sevoflurane-induced ET attenuation. This may lead to a positive feedback mechanism with augmented ROS generation to trigger APC secondary to altered mitochondrial function.

Author List

Riess ML, Kevin LG, McCormick J, Jiang MT, Rhodes SS, Stowe DF

Author

David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

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

Anesthesia
Anesthetics, Inhalation
Animals
Electron Transport
Enzyme Inhibitors
Fluorescence
Free Radical Scavengers
Free Radicals
Guinea Pigs
Heart
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Methyl Ethers
Mitochondria
Myocardium
NAD
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Reactive Oxygen Species