Anesthetic preconditioning: the role of free radicals in sevoflurane-induced attenuation of mitochondrial electron transport in Guinea pig isolated hearts.

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.

• Authors: Matthias L Riess, Leo G Kevin, Joseph McCormick, Ming T Jiang, Samhita S Rhodes, David F Stowe
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 100 Issue 1 Pg. 46-53 (Jan 2005) ISSN: 0003-2999 [Print] United States
• PMID: 15616050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anesthetics, Inhalation
• Enzyme Inhibitors
• Free Radical Scavengers
• Free Radicals
• Methyl Ethers
• Reactive Oxygen Species
• NAD
• Sevoflurane
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Anesthesia
• Anesthetics, Inhalation (pharmacology)
• Animals
• Electron Transport (drug effects)
• Enzyme Inhibitors (pharmacology)
• Fluorescence
• Free Radical Scavengers (pharmacology)
• Free Radicals (metabolism)
• Guinea Pigs
• Heart (drug effects)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• Methyl Ethers (pharmacology)
• Mitochondria (drug effects, metabolism)
• Myocardium (metabolism)
• NAD (metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Reactive Oxygen Species (metabolism)
• Sevoflurane