A high concentration of sevoflurane induces gasping breaths in mice
Introduction
Gasping, which is characterized by spasmodic inspiratory effort, is generated within the brain stem by an intrinsic mechanism and is the ‘last resort’ respiratory effort in response to severe hypoxia, which enhances oxygen and circulation (Adolph, 1969; Gershan et al., 1990; Guntheroth and Kawabori, 1975; St-John, 1990). The disruption of gasping control mechanisms has been hypothesized to contribute to a poor outcome of patients with Sudden Infant Death Syndrome (SIDS) (Thach, 2008) and cardiac arrest patients (Bobrow et al., 2008; Debaty et al., 2017).
In the course of animal experiments, we noticed that in mice inhalation of a high concentration of sevoflurane causes gasping-like respiration. In the previous studies, changes in breathing pattern such as an increase in tidal volume and/or a decrease in respiratory frequency (Cesarovic et al., 2010; Groeben et al., 2003) in response to increasing concentration of inhalational anesthetics including isoflurane and sevoflurane have been observed. However, there has been no mention of gasping-like respiration in these studies. Furthermore, there has been no study in which a similarity between hypoxia-induced gasping and inhalational anesthetics-induced gasping-like respiration was examined. The purpose of the present study is to compare the breathing pattern during the hypoxia-induced gasping with that of the sevoflurane-induced gasping-like respiration. If hypoxia-induced gasping and sevoflurane-induced gasping-like respiration are similar, it could be possible that both hypoxia-induced gasping and sevoflurane-induced gasping-like respiration are generated by the same intrinsic mechanism within the brainstem. In this perspective, we reasoned that there might be a positive interaction between sevoflurane and hypoxia in terms of generation of gasping on the same intrinsic mechanism.
Section snippets
Ethical approval
The present experiments were performed under the “Guiding Principle for the Care and Use of animals in the field of Physiological Sciences” recommended by the Physiological Society of Japan. All the experimental protocols were approved by the Committee on Animal Research at the University of Chiba (animal protocol number 1–227).
Animals
Fourteen adult male inbred mice (C57BL/6, Harlan, the Netherlands), housed in animal facilities at Chiba University, aged 12–38 weeks and weighing between 26−39 g were
Hypoxic stress
While the anesthesia was maintained at light level (0.7 minimum alveolar concentration: MAC) with inhalation of 2.3 % sevoflurane, the decreases in oxygen level of inhalational carrier gas caused considerable changes in breathing patterns (Figs. 1 and 2, Table 1). Although there were small changes in TE, VT, and VI values, no remarkable change in breathing patterns were observed when inhalational carrier gas was changed from hyperoxia gas (baseline condition) to normoxic gas. During inhalation
Discussion
This study evidenced that inhalation of a high concentration of sevoflurane (>1.5MAC) under hyperoxia can cause a gaping-like breathing pattern characterized by a big VT and a slow fR. This big VT correlates the increase in VT/TI and slow fR to prolongation of TE. Comparison of the values of time to reach peak inspiratory flow between deep level of sevoflurane anesthesia (1.5 MAC) and very deep level of sevoflurane anesthesia (2,0 MAC) showed that the values of time to reach peak inspiratory
Author contributions
T.N. conceived and designed research. T.N. and H.J. performed experiments. N.N–T. and S.I. helped formulate the study protocol. T.N., H.J., N. N–T., and S.I. interpreted results of experiments and approved the final version of the manuscript.
Declaration of Competing Interest
The authors declare no competing interests.
Acknowledgements
Support was provided solely from institutional and/or department sources. The authors are grateful to Dr. Sara Shimizu who greatly helped to improve the manuscript.
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