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Cited by 15Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyAnesthesia and Sedative Agents

Differential Increase of Mitochondrial Matrix Volume by Sevoflurane in Isolated Cardiac Mitochondria

Riess, Matthias L., Costa, Alexandre D., Carlson, Richard, Garlid, Keith D., Heinen, André, Stowe, David F.·2008·Anesthesia & Analgesia
DOI 10.1213/ane.0b013e318167875e
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Abstract

In Brief BACKGROUND: Mitochondrial (m) adenosine triphosphate sensitive potassium (KATP) 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 mKATP 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 mKATP channel opener, and by different sevoflurane concentrations, were measured by light absorption at 520 nm in the absence or presence of the mKATP channel blocker, 5-hydroxydecanoate. RESULTS: Compared with control, 30–300 μM 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 μM; 7.1 vol %), however, had no effect on MMV. CONCLUSIONS: In clinically relevant concentrations, sevoflurane increases MMV via mKATP 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. IMPLICATIONS: Maintenance of mitochondrial matrix volume due to potassium influx has been implicated in cardioprotection via KATP channel opening. Here, we show that sevoflurane increases mitochondrial matrix volume by opening KATP channels. These findings add to our understanding of the intracellular mechanisms of volatile anesthetics as cardioprotective drugs.

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Crossref · 10.1213/ane.0b013e318167875e

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Authors
Riess, M. L., Costa, A. D., Carlson, R., Garlid, K. D., Heinen, A., & Stowe, D. F.
Affiliations
  • Medical College of Wisconsin (US)
  • Portland State University (US)
Corresponding author
  • Riess, Matthias L.
  • Carlson, Richard
  • Heinen, André
ORCID
Venue
Anesthesia & Analgesia
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-04
Volume
106
Issue
4
Pages
1049-1055
ISSN
0003-2999 (ISSN-L)
DOI
10.1213/ane.0b013e318167875e
OpenAlex
W1985420589
Cited by
15
References
47
Citations by year
2022: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
1.42
Type
journal article
Language
en
Open access
closed
Locations
  • Anesthesia & Analgesia (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL-36573, HL-67842, HL 58691, R01HL058691, P01HL036573, R01HL067842)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Keywords
sevoflurane, mitochondrial KATP channels, cardioprotection, volatile anesthetics, ischemia-reperfusion injury, 5-hydroxydecanoate, diazoxide, heart mitochondria
MeSH terms
Sevoflurane, Adenosine Triphosphate, Animals, Female, Guinea Pigs, Heparin, Kinetics, Male, Methyl Ethers, Mitochondria, Heart, Valinomycin

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