Ventilator–induced coagulopathy in experimental Streptococcus pneumoniae pneumonia

¹ Interdepartmental Division of Critical Care Medicine
² Interdepartmental Division of Critical Care Medicine; Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.); and Dept of Intensive Care
³ Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.); Dept of Intensive Care; and Dept of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
⁴ Dept of Pathology, University of Toronto, Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
⁵ Dept of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands

^* To whom correspondence should be addressed. E-mail: jack.haitsma{at}utoronto.ca.

	Abstract

Pneumonia, the main cause of acute lung injury, is characterized by a local proinflammatory response and coagulopathy. Mechanical ventilation (MV) is often required. However, MV can lead to additional injury so-called ventilator-induced lung injury (VILI). Therefore, we investigated the effect of VILI on alveolar fibrin turnover in Streptococcus pneumoniae pneumonia.

Pneumonia was induced in rats, followed 48 hours later by either lung–protective MV (lower tidal volumes (V_T) and positive end–expiratory pressure; LV_T–PEEP) or MV causing VILI (high V_T, zero-PEEP; HV_T–ZEEP) for 3 hours. Non–ventilated pneumonia rats and healthy rats served as controls. Thrombin anti–thrombin complexes (TATc), as a measure for coagulation, and plasminogen activator activity, as a measure of fibrinolysis, were determined in bronchoalveolar lavage fluid (BALF) and serum.

Pneumonia was characterized by local (BALF) activation of coagulation, resulting in elevated TATc–levels and attenuation of fibrinolysis compared to healthy controls. LV_T–PEEP did not influence alveolar coagulation nor fibrinolysis. HV_T–ZEEP did intensify the local procoagulant response: TATc–levels rose significantly and levels of the main inhibitor of fibrinolysis, plasminogen activator inhibitor (PAI)–1, increased significantly. HV_T–ZEEP also resulted in systemic elevation of TATc compared to LV_T–PEEP.

MV causing VILI increases pulmonary coagulopathy in an animal model of S. pneumoniae pneumonia and results in systemic coagulopathy.