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Peripheral nerve conduction abnormalities precede morphological alterations in an experimental rat model of sepsis

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Abstract

Purpose

The pathological mechanisms of critical illness polyneuropathy (CIP), an acute neuromuscular disorder, remain unknown. In this study, we evaluated nerve and vascular properties that might account for electrophysiological abnormalities, including reduced nerve conduction amplitude, in the early phase of CIP.

Methods

Rats were administered intravenous saline (C-group; n = 31) or lipopolysaccharide (3 mg/kg/day; L-group; n = 30) for 48 h. Subsequently, tracheotomy was performed and sciatic nerves exposed bilaterally. A catheter was inserted into the left internal carotid artery to measure the mean arterial pressure (MAP). Nerve conduction velocity (NCV), nerve blood flow (NBF), evoked amplitudes, chronaxie, rheobase, and the absolute refractory period (ARP) were measured from the sciatic nerves. Degeneration, myelination, and neutrophil infiltration were examined in the sciatic nerves using histology and electron microscopy.

Results

The NBF (C-group 25 ± 3 ml/100 g/min, L-group 13 ± 3 ml/100 g/min, p < 0.001) was lower in the L-group, but the MAP was similar between groups (C-group 119 ± 17 mmHg, L-group 115 ± 18 mmHg, p = 0.773). LPS also caused a severe reduction in amplitude (C-group 0.9 ± 0.2 mV, L-group 0.2 ± 0.1 mV, p < 0.001), while latency and NCV were not affected. Of note, response amplitudes partially recovered with an increase in stimulus intensity. LPS treatment increased the rheobase and decreased the chronaxie (rheobase: C vs L-group; 0.35 ± 0.07 vs 1.29 ± 0.66 mA, p < 0.001; chronaxie 171 ± 24 vs 42 ± 20 µs, p < 0.001), while ARP was unchanged. No primary axonal degeneration or inflammatory infiltration was observed.

Conclusions

Our findings suggest that primary electrophysiological deterioration is due to threshold alterations rather than morphological alterations after 48 h of LPS treatment.

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Acknowledgments

We thank Prof. Tatsuo Akema for his helpful suggestions for the nerve conduction studies, and Dr. Masatomo Doi, Prof. Masayuki Takagi, and Prof. Mamoru Tadokoro for suggestions for pathology diagnosis using histology and electron microscopy. This research was supported by JSPS KAKENHI Grant Number 20592130.

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Authors and Affiliations

  1. Department of Anesthesia, Kanazawabunko Hospital, Kanagawa, Japan

    Arisa Miura

  2. Department of Anesthesiology, St. Marianna University School of Medicine, 2-16-1, Sugao Miyamae-ku, Kawasaki-shi, Kanagawa, 216-8511, Japan

    Hirofumi Hino, Kazuhide Uchida, Soichiro Inoue & Takeshi Tateda

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  1. Arisa Miura
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  2. Hirofumi Hino
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  3. Kazuhide Uchida
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  4. Soichiro Inoue
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  5. Takeshi Tateda
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Correspondence to Hirofumi Hino.

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Miura, A., Hino, H., Uchida, K. et al. Peripheral nerve conduction abnormalities precede morphological alterations in an experimental rat model of sepsis. J Anesth 30, 961–969 (2016). https://doi.org/10.1007/s00540-016-2247-5

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  • DOI: https://doi.org/10.1007/s00540-016-2247-5

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