Skip to main content
SpringerLink
Log in

Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane

  • Original Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Purpose

Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm.

Methods

Male adult C57BL/6 J mice were divided into eight groups (n = 8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6–12 or ZT18–24). Mice were anesthetized for 6 h using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n = 8–9 each).

Results

Phase shift after anesthesia at ZT6–12 using sevoflurane (− 0.49 h) was smaller compared with desflurane (− 1.1 h) and isoflurane (− 1.4 h) (p < 0.05). Clock mRNA (ZT6–12, p < 0.05) and Per2 mRNA (ZT18–24, p < 0.05) expression were different between the groups after anesthesia.

Conclusion

0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding autho, upon reasonable request.

References

  1. Allada R, Bass J. Circadian mechanisms in medicine. N Engl J Med. 2021;384:550–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ludin NM, Orts-Secastian A, Cheeseman JF, Chong J, Merry AF, Cuminet D, Yamazaki S, Pawley MDM, Warman GR. General anaesthesia shifts the murine circadian clock in a time-dependant fashion. Clocks Sleep. 2021;3:87–97.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Imai R, Makino H, Katoh T, Kurita T, Hokamura K, Umemura K, Nakajima Y. Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia. Sci Rep. 2020;10:18273. https://doi.org/10.1038/s41598-020-75434-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li N, Stanewsky R, Popay T, Warman G, Cheeseman J. The effect of general anaesthesia on circadian rhythms in behaviour and clock gene expression of drosophila melanogaster. Clocks Sleep. 2020;23(2):434–41.

    Article  Google Scholar 

  5. Kadota K, Iijima N, Hayashi Y, Takumi K, Higo S, Sakamoto A, Ozawa H. Time–dependent repression of mPer2 expression in the suprachiasmatic nucleus by inhalation anesthesia with sevoflurane. Neurosci Lett. 2012;528:153–8.

    Article  CAS  PubMed  Google Scholar 

  6. Challet E, Gourmelen S, Pevet P, Oberling P, Pain L. Reciprocal relationships between general (Propofol) anesthesia and circadian time in rats. Neuropsychopharmacology. 2007;32:728–35.

    Article  CAS  PubMed  Google Scholar 

  7. Wee BE, Turek FW. Midazolam, a short–acting benzodiazepine, resets the circadian clock of the hamster. Pharmacol Biochem Behav. 1989;32:901–6.

    Article  CAS  PubMed  Google Scholar 

  8. Montaigne D, Marechal X, Modine T, Coisne A, Mouton S, Fayad G, Ninni S, Klein C, Ortmans S, Seunes C, Potelle C, Berthier A, Gheeraert C, Piveteau C, Deprez R, Eeckhoute J, Duez H, Lacroix D, Deprez B, Jegou B, Koussa M, Edme JL, Lefebvre P, Staels B. Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single–centre propensity–matched cohort study and a randomised study. Lancet. 2018;391:59–69. https://doi.org/10.1016/S0140-6736(17)32132-3.

    Article  PubMed  Google Scholar 

  9. Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T, Takahashi JS. Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012;338:349–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Abrahamson EE, Moore RY. Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res. 2001;916:172–91.

    Article  CAS  PubMed  Google Scholar 

  11. Mori K, Iijima N, Higo S, Aikawa S, Matsuo I, Takumiet K, Sakamoto A, Ozawa H. Epigenetic suppression of mouse Per2 expression in the suprachiasmatic nucleus by the inhalational anesthetic, sevoflurane. PLoS One. 2014;9(1):e87319. https://doi.org/10.1371/journal.pone.0087319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cheeseman JF, Winnebeck EC, Millar CD, Kirkland LS, Sleigh J, Goodwin M, Pawley MDM, Bloch G, Lehmann K, Menzel R, Warman GR. General anesthesia alters time perception by phase shifting the circadian clock. Proc Natl Acad Sci U S A. 2012;109:7061–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sonner JM, Gong D, Li J, Eger EI, Laster MJ. Mouse strain modestly influences minimum alveolar anesthetic concentration and convulsivity of inhaled compounds. Anesth Analg. 1999;89:1030–4.

    Article  CAS  PubMed  Google Scholar 

  14. Sato Y, Kobayashi E, Murayama T, Mishina M, Seo N. Effect of N–methyl–D–aspartate receptor epsilon1 subunit gene disruption of the action of general anesthetic drugs in mice. Anesthesiology. 2005;102:557–61.

    Article  CAS  PubMed  Google Scholar 

  15. Quasha AL, Eger EI, Tinker TH. Determination and applications of MAC. Anesthesiology. 1980;53:315–34.

    Article  CAS  PubMed  Google Scholar 

  16. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.

    Article  PubMed  Google Scholar 

  17. Anzai M, Iijima N, Higo S, Takumi K, Matsuo I, Mori K, Ohe Y, Kadota K, Akimoto T, Sakamoto A, Ozawa H. Direct and specific effect of sevoflurane anesthesia on rat Per2 expression in the suprachiasmatic nucleus. PLoS One. 2013;8(3):e59454. https://doi.org/10.1371/journal.pone.0059454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ludin NM, Cheeseman JF, Merry AF, Millar CD, Warman GR. The effects of the general anaesthetic isoflurane on the honey bee (Apis mellifera) circadian clock. Chronobiol Int. 2016;33:128–33.

    Article  CAS  PubMed  Google Scholar 

  19. Xia T, Cui Y, Chu S, Ma S, Gu X. Murine clock gene expression in the suprachiasmatic nuclei and peripheral blood mononuclear cells during the daily sleep–wake rhythm and after isoflurane anesthesia. Sleep Biol Rhythms. 2015;13:357–65.

    Article  Google Scholar 

  20. Xu Y, Tang P, Zhang W, Firestone L, Winter PM. Fluorine–19 nuclear magnetic resonance imaging and spectroscopy of sevoflurane uptake, distribution, and elimination in rat brain. Anesthesiology. 1995;83:766–74.

    Article  CAS  PubMed  Google Scholar 

  21. Venkatasubramanian PN, Shen YJ, Wyrwicz AM. Characterization of the cerebral distribution of general anesthetics in vivo by two–dimensional 19F chemical shift imaging. Magn Reson Med. 1996;35:626–30.

    Article  CAS  PubMed  Google Scholar 

  22. Kinjo S, Lim E, Magsaysay MV, Sands LP, Leung JM, Perioperative Medicine Research Group. Volatile anaesthetics and postoperative delirium in older surgical patients—a secondary analysis of prospective cohort studies. Acta Anaesthesiol Scand. 2019;63:18–26.

    Article  CAS  PubMed  Google Scholar 

  23. Chen G, Zhou Y, Shi Q, Zhou H. Comparison of early recovery and cognitive function after desflurane and sevoflurane anaesthesia in elderly patients: A meta–analysis of randomized controlled trials. J Int Med Res. 2015;43:619–28.

    Article  CAS  PubMed  Google Scholar 

  24. Rampil IJ. Anesthetic potency is not altered after hypothermic spinal cord transection in rats. Anesthesiology. 1994;80:606–10.

    Article  CAS  PubMed  Google Scholar 

  25. Katoh T, Suguro Y, Nakajima R, Kazama T, Ikeda K. Blood concentrations of sevoflurane and isoflurane on recovery from anaesthesia. Br J Anaesth. 1992;69:259–62.

    Article  CAS  PubMed  Google Scholar 

  26. Dwyer R, Bennett HL, Eger EI, Heilbron D. Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. Anesthesiology. 1992;77:888–98.

    Article  CAS  PubMed  Google Scholar 

  27. Chortkoff BS, Eger EI 2nd, Crankshaw DP, Gonsowski CT, Dutton RC, Ionescu P. Concentrations of desflurane and propofol that suppress response to command in humans. Anesth Analg. 1995;81:737–43.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Rachel James, PhD ELS, from Edanz (https://jp.edanz.com/ac) and Mohamed Mthear Sahib Ibrahim Khaleelullah, PhD, Hamamatsu University School of Medicine for editing a draft of this manuscript.

Funding

This research was supported by grants-in-aid for scientific research (C) (grants 22K09044) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Tokyo, Japan).

Author information

Author notes

  1. Sho Sugimura and Ryo Imai contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Sho Sugimura, Ryo Imai, Takasumi Katoh, Hiroshi Makino, Tadayoshi Kurita, Yasuhito Suzuki, Yoshitaka Aoki, Tetsuro Kimura & Yoshiki Nakajima

  2. Department of Medical Education, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuya Hokamura

  3. Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuo Umemura

Authors
  1. Sho Sugimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryo Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takasumi Katoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroshi Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuya Hokamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tadayoshi Kurita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuhito Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshitaka Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tetsuro Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kazuo Umemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshiki Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SS, RI and TK. The first draft of the manuscript was written by SS and RI and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sho Sugimura.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 10563 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sugimura, S., Imai, R., Katoh, T. et al. Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane. J Anesth 38, 10–18 (2024). https://doi.org/10.1007/s00540-023-03262-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-023-03262-9

Keywords

Search

Navigation