Attenuation of mitochondrial respiration by sevoflurane in isolated cardiac mitochondria is mediated in part by reactive oxygen species.
BACKGROUND
Anesthetic preconditioning protects against cardiac ischemia/reperfusion injury. Increases in reduced nicotinamide adenine dinucleotide and reactive oxygen species during sevoflurane exposure suggest attenuated mitochondrial electron transport as a trigger of anesthetic preconditioning. The authors investigated the effects of sevoflurane on respiration in isolated cardiac mitochondria.


METHODS
Mitochondria were isolated from fresh guinea pig hearts, and mitochondrial oxygen consumption was measured in the presence of complex I (pyruvate) or complex II (succinate) substrates. The mitochondria were exposed to 0, 0.13, 0.39, 1.3, or 3.9 mM sevoflurane. State 3 respiration was determined after adenosine diphosphate addition. The reactive oxygen species scavengers manganese(III) tetrakis (4-benzoic acid) porphyrin chloride and N-tert-Butyl-a-(2-sulfophenyl)nitrone sodium (10 microM each), or the K(ATP) channel blockers glibenclamide (2 microM) or 5-hydroxydecanoate (300 microM), were given alone or before 1.3 mM sevoflurane.


RESULTS
Sevoflurane attenuated respiration for both complex I and complex II substrates, depending on the dose. Glibenclamide and 5-hydroxydecanoate had no effect on this attenuation. Both scavengers, however, abolished the sevoflurane-induced attenuation for complex I substrates, but not for complex II substrates.


CONCLUSIONS
The findings suggest that sevoflurane-induced attenuation of complex I is mediated by reactive oxygen species, whereas attenuation of other respiratory complexes is mediated by a different mechanism. The opening of mitochondrial K(ATP) channels by sevoflurane does not seem to be involved in this effect. Thus, reactive oxygen species formation may not only result from attenuated electron transport by sevoflurane, but it may also contribute to complex I attenuation, possibly leading to a positive feedback and amplification of sevoflurane-induced reactive oxygen species formation in triggering anesthetic preconditioning.
Riess
Matthias L
ML
Anesthesiology Research Laboratories, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Eells
Janis T
JT
Kevin
Leo G
LG
Camara
Amadou K S
AK
Henry
Michele M
MM
Stowe
David F
DF
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels; D011773:Pyruvates / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077149:Sevoflurane; D013386:Succinates / Q000378:metabolism
D018685:Anesthetics, Inhalation; D016166:Free Radical Scavengers; D008565:Membrane Proteins; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011773:Pyruvates; D017382:Reactive Oxygen Species; D013386:Succinates; C117780:mitochondrial K(ATP) channel; D000077149:Sevoflurane; D005905:Glyburide