Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but not inflammation

Abstract

Pulmonary coagulopathy and hyperinflammation may contribute to an adverse outcome in sepsis. The present study determines the effects of natural inhibitors of coagulation on bronchoalveolar haemostasis and inflammation in a rat model of endotoxaemia.Male Sprague-Dawley rats were randomised to treatment with normal saline, recombinant human activated protein C (APC), plasma-derived antithrombin (AT), recombinant human tissue factor pathway inhibitor (TFPI), heparin or recombinant tissue plasminogen activator (tPA). Rats were intravenously injected with lipopolysaccharide (LPS), which induced a systemic inflammatory response and pulmonary inflammation. Blood and bronchoalveolar lavage were obtained at 4 and 16 h after LPS injection, and markers of coagulation and inflammation were measured.LPS injection caused an increase in the levels of thrombin-AT complexes, whereas plasminogen activator activity was attenuated, both systemically and within the bronchoalveolar compartment. Administration of APC, AT and TFPI significantly limited LPS-induced generation of thrombin-AT complexes in the lungs, and tPA stimulated pulmonary fibrinolytic activity. However, none of the agents had significant effects on the production of pulmonary cytokines, chemokines, neutrophil influx and myeloperoxidase activity.Natural inhibitors of coagulation prevent bronchoalveolar activation of coagulation, but do not induce major alterations of the pulmonary inflammatory response in rat endotoxaemia.

Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model

“…Activation of coagulation and impairment of fibrinolysis have been found in ALI/acute respiratory distress syndrome as the result of many causes, including sterile inflammation as well as infection. 17,21,[39][40][41] From this point of view, TRALI may be regarded as part of the ALI/acute respiratory distress syndrome and not as a separate entity, as suggested previously. [5][6][7] In line with this, we recently found that TRALI contributes to mortality in critically ill patients, 7 suggesting that prognosis of TRALI is not as favorable as generally considered but rather may parallel ALI as the result of other causes, at least in certain patient populations.…”

ExoU-induced procoagulant activity inPseudomonas aeruginosa-infected airway cells

“…antithrombin and the protein C system) and fibrinolytic activity, caused by high levels of plasminogen activator inhibitor-1 and reduced levels of plasminogen activator activity, as described by CHOI and coworkers [24,25] in patients with ventilator-asociated pneumonia and experimental pneumonia in rats.…”

Nebulized Anticoagulants Limit Pulmonary Coagulopathy, But Not Inflammation, in a Model of Experimental Lung Injury

“…(12) Previous animal studies specifically targeting pulmonary coagulopathy showed systemic treatment with anticoagulants to attenuate pulmonary coagulopathy with lung injury. (13)(14)(15) However, systemic treatment with anticoagulants, of course, also affected systemic coagulation. In the present study we investigated the effect of locally administered anticoagulants on pulmonary procoagulant and proinflammatory responses to LPS in a rat model of sepsis-induced lung injury.…”