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Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice

Abstract

Employment of anesthetics, including isoflurane, though mandatory in animal experiments, is often regarded as a major limitation because results obtained with anesthetics may be different from those obtained under a conscious state. This study re-visits two issues related to the use of isoflurane. First, does isoflurane exert depression equally on all aspects of cardiovascular functions and their regulations? Second, is the circulatory supply of oxygen to brain tissues sufficient under isoflurane anesthesia? We determined in male C57BL/6J mice the temporal effects of 1.5% (vol/vol) isoflurane on blood pressure (BP), heart rate (HR), cardiac performance, baroreflex-mediated sympathetic vasomotor tone, cardiac vagal baroreflex, functional connectivity within the baroreflex neural circuits, carotid or cerebral blood flow, cortical tissue oxygen level, respiratory rate and blood gas. Over 150 min after exposure to 1.5% isoflurane, BP and HR were sustained at 71% and 79% of their awake levels amid a trend of progressive increase. Cardiac performance was within physiological ranges. Baroreflex-mediated sympathetic vasomotor tone gradually reversed from an 85% reduction toward the conscious level, alongside a parallel decrease in inhibitory connectivity between nucleus tractus solitarii (NTS) and rostral ventrolateral medulla. A decline in excitatory connectivity between NTS and nucleus ambiguus accompanied the decrease in cardiac vagal baroreflex. There were progressive increases in carotid or cerebral blood flow and tissue oxygen tension in cerebral cortex, alongside gradual hypoventilation, mild respiratory acidosis and hypercapnia. We conclude that, by eliciting disproportional depressive actions on cardiovascular functions and their regulations, which sustain circulatory supply of oxygen to brain tissues, 1.5% isoflurane is sufficient to maintain optimal cardiovascular functions in mice.

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Fig. 1: Experimental set up.
Fig. 2: Temporal changes in mean arterial pressure (MAP), HR, power density of the low-frequency component in the systolic BP spectrum (BLF), baroreflex sensitivity (BRS), RR and baroreflex effectiveness index (BEI) in mice from an awake, resting state (C) to under 1.5% (vol/vol) isoflurane for 150 min.
Fig. 3: Temporal changes in functional connectivity within baroreflex neural circuits in mice under 1.5% (vol/vol) isoflurane for 150 min.
Fig. 4: Temporal changes in carotid blood flow (CBF), tissue oxygen tension (PO2), tissue perfusion (Flow) and tissue temperature in the cerebral cortex of mice subjected to 1.5% (vol/vol) isoflurane for 150 min.

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The data that support the findings of this study may be sought from the corresponding author under the author’s discretion.

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Acknowledgements

This study was supported in part by research grants MOST-107-2320-B-182A-024, MOST-108-2320-B-182A-007 and MOST-109-2320-B-182A-019 to S.H.H.C. from the Ministry of Science and Technology, Taiwan.

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Y.-Y.P., C.-Y.T., S.H.H.C. and J.Y.H.C. conceived and designed the study. Y.-H.H. and J.C.C.W. collected the data. Y.-Y.P., C.-Y.T., Y.-H.H. and J.C.C.W. analyzed the data. All authors wrote the manuscript.

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Correspondence to Samuel H. H. Chan or Julie Y. H. Chan.

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Poon, YY., Tsai, CY., Huang, Y. et al. Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice. Lab Anim 50, 26–31 (2021). https://doi.org/10.1038/s41684-020-00684-w

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