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Journal of Anesthesia

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01-12-2014 | Original Article

Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency

Authors: Suzanne Roelofs, Ganesh R. Manjeri, Peter H. Willems, Gert Jan Scheffer, Jan A. Smeitink, Jacques J. Driessen

Published in: Journal of Anesthesia | Issue 6/2014

Abstract

Background

Children with mitochondrial disorders are frequently anesthetized for a wide range of operations. These disorders may interfere with the response to surgery and anesthesia. We examined anesthetic sensitivity to and respiratory effects of isoflurane in the Ndufs4 knockout (KO) mouse model. These mice exhibit an isolated mitochondrial complex I (CI) deficiency of the respiratory chain, and they also display clinical signs and symptoms resembling those of patients with mitochondrial CI disease.

Methods

We investigated seven Ndufs4^−/− knockout (KO), five Ndufs4^+/− heterozygous (HZ) and five Ndufs4^+/+ wild type (WT) mice between 22 and 25 days and again between 31 and 34 days post-natal. Animals were placed inside an airtight box, breathing spontaneously while isoflurane was administered in increasing concentrations. Minimum alveolar concentration (MAC) was determined with the bracketing study design, using the response to electrical stimulation to the hind paw.

Results

MAC for isoflurane was significantly lower in KO mice than in HZ and WT mice: 0.81 % ± 0.01 vs 1.55 ± 0.05 % and 1.55 ± 0.13 %, respectively, at 22–25 days, and 0.65 ± 0.05 %, 1.65 ± 0.08 % and 1.68 ± 0.08 % at 31–34 days. The KO mice showed severe respiratory depression at lower isoflurane concentrations than the WT and HZ mice.

Conclusion

We observed an increased isoflurane anesthetic sensitivity and severe respiratory depression in the KO mice. The respiratory depression during anesthesia was strongly progressive with age. Since the pathophysiological consequences from complex I deficiency are mainly reflected in the central nervous system and our mouse model involves progressive encephalopathy, further investigation of isoflurane effects on brain mitochondrial function is warranted.

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Title: Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency
Authors: Suzanne Roelofs
Ganesh R. Manjeri
Peter H. Willems
Gert Jan Scheffer
Jan A. Smeitink
Jacques J. Driessen
Publication date: 01-12-2014
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 6/2014
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-014-1791-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Isoflurane anesthetic hypersensitivity and progressive respiratory depression in a mouse model with isolated mitochondrial complex I deficiency

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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