Thrombomodulin protects against lung damage created by high level of oxygen with large tidal volume mechanical ventilation in ratsReport as inadecuate




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Journal of Intensive Care

, 2:57

First Online: 01 October 2014Received: 10 June 2014Accepted: 17 September 2014

Abstract

BackgroundVentilator-induced lung injury VILI is associated with inflammatory responses in the lung. Thrombomodulin TM, a component of the coagulation system, has anticoagulant and anti-inflammatory effects. We hypothesized that the administration of recombinant human soluble TM rhsTM would block the development of lung injury.

MethodsLung injury was induced by high tidal volume ventilation for 2 h with 100% oxygen in rats. Rats were ventilated with a tidal volume of 35 ml-kg with pretreatment via a subcutaneous injection of 3 mg-kg rhsTM HV high tidal volume-TM or saline HV-SAL 12 h before mechanical ventilation. Rats ventilated with a tidal volume of 6 ml-kg under 100% oxygen with rhsTM LV low tidal volume-TM or saline LV-SAL were used as controls. Lung protein permeability was determined by Evans blue dye EBD extravasation.

ResultsLung injury was successfully induced in the HV-SAL group compared with the LV-SAL group, as shown by the significant decrease in arterial oxygen pressure PaO2, increased protein permeability, and increase in mean pulmonary artery pressure mPAP and ratio of mean pulmonary artery pressure to mean artery pressure Pp-Ps. Treatment of rats with lung injury with rhsTM HV-TM significantly attenuated the decrease in PaO2 and the increase in both mPAP and Pp-Ps, which was associated with a decrease in the lung protein permeability. Lung tissue mRNA expressions of interleukin IL-1α, IL-1β, IL-6, tumor necrosis factor-α, and macrophage inflammatory protein MIP-2 were significantly higher in HV than in LV rats. Rats with VILI treated with rhsTM HV-TM had significantly lower mRNA expressions of IL-1α, IL-1β, IL-6, and MIP-2 than those expressions in HV-SAL rats.

ConclusionsAdministration of rhsTM may prevent the development of lung injury created by high level of oxygen with large tidal volume mechanical ventilation, which has concomitant decrease in proinflammatory cytokine and chemokine expression in the lung.

KeywordsVentilator-induced lung injury Thrombomodulin Pulmonary hypertension Nitric oxide Electronic supplementary materialThe online version of this article doi:10.1186-s40560-014-0057-0 contains supplementary material, which is available to authorized users.

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Author: Yoshiaki Iwashita - Erquan Zhang - Junko Maruyama - Ayumu Yokochi - Yasuharu Yamada - Hirofumi Sawada - Yoshihide Mitani -

Source: https://link.springer.com/







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