Dataset Information

Esmolol indirectly stimulates vagal nerve activity in endotoxemic pigs.

ABSTRACT:

Background

There is an increasing interest in beta-blockade as a therapeutic approach to sepsis following consistent experimental findings of attenuation of inflammation and improved survival with beta1 selective antagonist. However, the mechanism of these beneficial effects remains very uncertain. Thus, this study is aimed at investigating the effects of a beta-1 selective blockade on sympathetic/parasympathetic activity in endotoxin-challenged pigs using heart rate variability. The hypothesis is that an adrenergic blockade could promote parasympathetic activity. Indeed, the increase of parasympathetic activity is a mechanism recently described as beneficial in septic states.

Methods

Fifty-one endotoxin-challenged pigs were studied. After 30 min of endotoxin infusion and 30 min of evolution without intervention, the pigs were randomly assigned the placebo or esmolol treatment and were observed for 200 min. Overall heart rate variability was assessed continuously, in the temporal domain by standard deviation of RR intervals (SDNN, ms),and in the frequency domain by spectral powers of low frequency (LF, ms²?×?10³/Hz) and high frequency (HF, ms²?×?10³/Hz) bands.

Results

Variations of power in these frequency bands were interpreted as putative markers of sympathetic (LF) and parasympathetic (HF) activity. In LPS treated animals, Esmolol did not increase SDNN, but instead decreased LF and increased HF power.

Conclusion

These spectral modifications associated to a beta-blocker treatment after an endotoxemic challenge are interpreted as a significant decrease of sympathetic activity and an indirect increase of vagal autonomic tone.

SUBMITTER: Aboab J

PROVIDER: S-EPMC6031554 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Esmolol indirectly stimulates vagal nerve activity in endotoxemic pigs.

Aboab Jerome J Mayaud Louis L Sebille Veronique V de Oliveira Rodrigo R Jourdain Merce M Annane Djillali D

Intensive care medicine experimental 20180704 1

<h4>Background</h4>There is an increasing interest in beta-blockade as a therapeutic approach to sepsis following consistent experimental findings of attenuation of inflammation and improved survival with beta1 selective antagonist. However, the mechanism of these beneficial effects remains very uncertain. Thus, this study is aimed at investigating the effects of a beta-1 selective blockade on sympathetic/parasympathetic activity in endotoxin-challenged pigs using heart rate variability. The hyp ...[more]

PMID: 29974363

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Project description:Vagal Nerve Stimulation (VNS) Therapy® is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are unclear. We hypothesized that one mechanism involves neuronal activity-dependent modifications of central nervous system excitatory synapses. To begin to test this hypothesis, we asked whether VNS modifies the activity of neurons in amygdala and hippocampus. Neuronal recordings from adult, freely moving rats revealed that activity in both amygdala and hippocampus was modified by VNS immediately after its application, and changes were detected following 1 week of stimulation. To investigate whether VNS modifies the proteome of excitatory synapses, we established a label-free, quantitative liquid chromatography-tandem mass spectrometry workflow that enables global analysis of the constituents of the postsynaptic density (PSD) proteome. PSD proteins were biochemically purified from amygdala/piriform cortex of VNS- or dummy-treated rats following 1-week stimulation, and individual PSD protein levels were quantified by liquid chromatography-tandem mass spectrometry analysis. We identified 1899 unique peptides corresponding to 425 proteins in PSD fractions, of which expression levels of 22 proteins were differentially regulated by VNS with changes greater than 150%. Changes in a subset of these proteins, including significantly increased expression of neurexin-1α, cadherin 13 and voltage-dependent calcium channel α2δ1, the primary target of the antiepileptic drug gabapentin, and decreased expression of voltage-dependent calcium channel γ3, were confirmed by western blot analysis of PSD samples. These results demonstrate that VNS modulates excitatory synapses through regulating a subset of the PSD proteome. Our study reveals molecular targets of VNS and point to possible mechanisms underlying its beneficial effects, including activity-dependent formation of excitatory synapses.

Dataset Information

Esmolol indirectly stimulates vagal nerve activity in endotoxemic pigs.

Background

Methods

Results

Conclusion

Publications

Esmolol indirectly stimulates vagal nerve activity in endotoxemic pigs.

Similar Datasets

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