Differential increase of mitochondrial matrix volume by sevoflurane in isolated cardiac mitochondria.
BACKGROUND
Mitochondrial (m) adenosine triphosphate sensitive potassium (K(ATP)) channel opening has been reported to trigger and/or mediate cardioprotection by volatile anesthetics. However, the effects of volatile anesthetics on mitochondrial function are not well understood. Prevention of mitochondrial matrix volume (MMV) contraction during ischemia may contribute to cardioprotection against ischemia/reperfusion injury. We investigated whether sevoflurane increases MMV and if this increase is mediated by mK(ATP) channel opening.


METHODS
Mitochondria from fresh guinea pig hearts were isolated and diluted in buffer that included oligomycin and ATP to inhibit ATP synthesis. Changes in MMV by diazoxide, a known mK(ATP) channel opener, and by different sevoflurane concentrations, were measured by light absorption at 520 nm in the absence or presence of the mK(ATP) channel blocker, 5-hydroxydecanoate.


RESULTS
Compared with control, 30-300 microM sevoflurane (approximately 0.2-2.1 vol %) increased MMV by 30%-55%, which was similar to the effect of diazoxide. These increases were blocked by 5-hydroxydecanoate. Higher sevoflurane concentration (1000 microM; 7.1 vol %), however, had no effect on MMV.


CONCLUSIONS
In clinically relevant concentrations, sevoflurane increases MMV via mK(ATP) channel opening. Preservation of mitochondrial integrity may contribute to the cardioprotective effects of sevoflurane against ischemia/reperfusion injury. Impaired mitochondrial function at supraclinical anesthetic concentrations may explain the observed biphasic response. These findings add to our understanding of the intracellular mechanisms of volatile anesthetics as cardioprotective drugs.
Riess
Matthias L
ML
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA. mriess@mcw.edu
Costa
Alexandre D
AD
Carlson
Richard
R
Garlid
Keith D
KD
Heinen
André
A
Stowe
David F
DF
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure*; D000077149:Sevoflurane; D014634:Valinomycin / Q000494:pharmacology
D008738:Methyl Ethers; D014634:Valinomycin; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D006493:Heparin