Research Article: Hypercapnia attenuates ventilator-induced lung injury through vagus nerve activation1

Date Published: November 25, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em
Cirurgia

Author(s): Wenfang Xia, Guang Li, Zhou Pan, Qingshan Zhou.

http://doi.org/10.1590/s0102-865020190090000002

Abstract

To investigate the role of vagus nerve activation in the protective effects
of hypercapnia in ventilator-induced lung injury (VILI) rats.

Male Sprague-Dawley rats were randomized to either high-tidal volume or
low-tidal volume ventilation (control) and monitored for 4h. The high-tidal
volume group was further divided into either a vagotomy or sham-operated
group and each surgery group was further divided into two subgroups:
normocapnia and hypercapnia. Injuries were assessed hourly through
hemodynamics, respiratory mechanics and gas exchange. Protein concentration,
cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid
(BALF), lung wet-to-dry weight and pathological changes were examined. Vagus
nerve activity was recorded for 1h.

Compared to the control group, injurious ventilation resulted in a decrease
in PaO2/FiO2 and greater lung static compliance, MPO
activity, enhanced BALF cytokines, protein concentration, cell count, and
histology injury score. Conversely, hypercapnia significantly improved VILI
by decreasing the above injury parameters. However, vagotomy abolished the
protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced
efferent vagus nerve activity compared to normocapnia.

These results indicate that the vagus nerve plays an important role in
mediating the anti-inflammatory effect of hypercapnia on VILI.

Partial Text

Mechanical ventilation (MV) is the primary means of treating acute respiratory
distress syndrome (ARDS)1. MV improves airway injury and oxygenation, but can cause or aggravate lung
injury leading to ventilator-induced lung injury (VILI)2. Lung protection ventilation strategies such as reducing tidal volume and
increasing positive end-expiratory pressure (PEEP) levels can increase the survival
rate in ARDS patients3. However, these measures can lead to elevated PaCO2, resulting in
hypercapnia (HPC) which has previously been considered an adverse side effect of
lung protection ventilation strategies. However, recent studies have shown that HPC
can have a protective effect on multiple organs, and that the application of
hypercapnia can improve ALI/ARDSs4. In addition, hypercapnic acidosis can directly attenuate experimental acute
lung injuries induced by ischemia-reperfusion5, free radicals6, endotoxins7, systemic sepsis8, and VILI both ex vivo and in vivo9. These studies indicate that hypercapnic acidosis may reduce lung injury
through the inhibition of the nuclear factor-κB inhibitor IκBα and the reduction of
cytokines through anti-inflammatory mechanisms10.

All animal procedures adhered to the Guide for the Care and Use of Laboratory
Animals, and were performed in accordance with the ethics committee of the Wuhan
University.

The main findings of this study are as follows: (1) Injurious MV for 4 h is
associated with pulmonary edema, increased levels of BALF inflammatory cytokines
TNF-α and IL-8, neutrophil counts, MPO activity, and structural damage. (2)
Therapeutic hypercapnia retained the lung wet-to-dry weight ratio, BALF protein
content, TNF-α and IL-8 levels, and lung injury score to control level. (3) Vagotomy
after VILI abolished the protective effects of hypercapnia. Our data suggest that
hypercapnia plays an important role in the protection of VILI through the activation
of the vagus nerve.

The vagus nerve is at least partially responsible for the anti-inflammatory effects
of HPC on VILI. These findings will facilitate further investigation of potential
therapeutic approaches for VILI and other inflammatory diseases. Our findings,
together with previous research, suggest that the cholinergic anti-inflammation
pathway may be a mechanism for the attenuation of VILI. Further studies are needed
to better understand the complex protective mechanism of HPC on VILI.

 

Source:

http://doi.org/10.1590/s0102-865020190090000002

 

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