Activation of vagovagal reflex prevents hepatic ischaemia–reperfusion‐induced lung injury via anti‐inflammatory and antioxidant effects

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Abstract
New Findings: What is the central question of this study? Does vagus nerve stimulation have protective effects against both direct liver damage and distant lung injury in a rat model of hepatic ischaemia–reperfusion? What is the main finding and its importance? Vagus nerve stimulation provides protection through anti‐inflammatory and anti‐oxidative stress effects, possibly achieved by the vagovagal reflex. Hepatic ischaemia–reperfusion (I/R) is not an isolated event; instead, it can result in remote organ dysfunction. The aim of this study was to investigate whether vagus nerve stimulation (VNS) can alleviate hepatic I/R‐induced lung injury and to explore the underlying mechanism. Thirty male Sprague–Dawley rats were randomly allocated into five groups (n = 6 each): the sham group (without I/R or VNS), the I/R group (hepatic I/R) and three different VNS treatment groups (hepatic I/R plus VNS). The hepatic I/R group was subjected to occlusion of the portal vein and hepatic artery for 1 h, followed by 6 h of reperfusion. The intact afferent and efferent cervical vagus nerves were stimulated throughout the I/R process. During VNS, cervical neural activity was recorded. At the end of the experiment, liver function, the wet‐to‐dry lung weight ratio, histology of the liver and lung and inflammatory/oxidative indices were evaluated. We found that VNS significantly mitigated lung injury, as demonstrated by alleviation of pulmonary oedema and pathological alterations, by limiting inflammatory cytokine infiltration and increasing antioxidant capability. This proof‐of‐concept study suggested that VNS might protect patients from lung injury induced by hepatic I/R related to various circumstances.

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