Fluid-induced lung injury—role of TRPV4 channels

Shailesh Bihari, Dani Dixon, Mark Lawrence, Dylan De Bellis, Claudine Bonder, David Dimasi, Andrew Bersten

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)


    Administration of bolus intravenous fluid is associated with respiratory dysfunction and increased mortality, findings with no clear mechanistic explanation. The objective of this study was to examine whether bolus intravenous (i.v.) fluid administration results in acute lung injury in a rat model and further, to examine whether this injury is associated with transient receptor potential vallinoid (TRPV)4 channel function and endothelial inflammatory response. Healthy male Sprague-Dawley rats were administered 60 ml/kg 0.9% saline i.v. over 30 min. Manifestation of acute lung injury was assessed by lung physiology, morphology, and markers of inflammation. The role of TRPV4 channels in fluid-induced lung injury was subsequently examined by the administration of ruthenium red (RR) in this established rat model and again in TRPV4 KO mice. In endothelial cell culture, permeability and P-selectin expression were measured following TRPV4 agonist with and without antagonist; 0.9% saline resulted in an increase in lung water, lavage protein and phospholipase A 2, and plasma angiopoietin-2, with worsening in arterial blood oxygen (PaO 2), lung elastance, surfactant activity, and lung histological injury score. These effects were ameliorated following i.v. fluid in rats receiving RR. TRPV4 KO mice did not develop lung edema. Expression of P-selectin increased in endothelial cells following administration of a TRPV4 agonist, which was ameliorated by simultaneous addition of RR. Bolus i.v. 0.9% saline resulted in permeability pulmonary edema. Data from ruthenium red, TRPV4 KO mice, and endothelial cell culture suggest activation of TRPV4 and release of angiopoietin 2 and P-selectin as the central mechanism.

    Original languageEnglish
    Pages (from-to)1121-1134
    Number of pages14
    Issue number9
    Early online date2017
    Publication statusPublished - 1 Sep 2017


    • 0.9% saline, angiopoietin 2, P-selectin
    • Fluids
    • Lung injury
    • Lung mechanics
    • Surfactants
    • TRPV4


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