Generation of mediators by limited proteolysis during blood coagulation and fibrinolysis--its pathogenetic role in the adult respiratory distress syndrome (ARDS)
Neuhof, H.; Seeger, W.; Wolf, H.R.
Resuscitation 14(1-2): 23-32
Products of blood coagulation and fibrinolysis, which are generated by limited proteolysis are able to effect the pulmonary circulation and gas exchange by biochemically mediated actions. Thrombin, fibrin and its degradation products provoke functional and morphological changes in the vessel wall. Fibrinopeptides, fibrin monomers and fibrin(ogen) degradation products induce vascoconstriction and vascular leakage. The vasoconstricting action of fibrin monomers is mediated by thromboxane A2 (TXA2) which is synthetized in the lung tissue itself. Thromboxane synthesis is stimulated by fibrin monomers only in the pulmonary circulation and not in the systemic circulation. Besides their vascular effects, fibrin monomers disturb the function of the surfactant components and increase the surface tension in surfactant monolayers. Proteinase inhibition as a general prophylactic and therapeutic concept with adult respiratory distress syndrome (ARDS) has to include the system of blood coagulation and fibrinolysis predominantly to prevent or stop the generation of products which are able to induce pulmonary vasoconstriction, vascular leakage and impairment of pulmonary gas exchange.