Effects of inhaled plasminogen activator on the balance between coagulation and fibrinolysis in traumatized pigs.
A profibrinolytic state is normal in the alveoli, but this may change as a result of trauma, possibly leading to fibrin deposition, a characteristic of acute lung injury/acute respiratory distress syndrome. Therefore, the present study investigated in a double-blind, placebo-controlled manner the effect of severe trauma on the alveolar fibrinolytic/coagulation balance, and the effect here-upon of inhalation of single-chain urokinase plasminogen activator (scu-PA) in pigs. The study shows an increased concentration of scu-PA in the bronchoalveolar lavage fluid of the treated animals in association with an increased plasmin-dependent fibrinolytic activity without increased systemic fibrinolytic activity, the transient increase in the concentration of scu-PA in the plasma being minimal. In conclusion, the study shows that activatable scu-PA can be nebulized to the lower respiratory tract and can increase the alveolar fibrinolysis without any significant systemic effects.
Münster
A-M B
AM
Department of Thrombosis Research, University of Southern Denmark, Esbjerg, Denmark. KBAR@ribeamt.dk
Rasmussen
L
L
Sidelmann
J
J
Ingemann Jensen
J
J
Bech
B
B
Gram
J
J
D000280:Administration, Inhalation; D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid; D004353:Drug Evaluation, Preclinical; D005342:Fibrinolysis / Q000187:drug effects; D010919:Placebos; D011650:Pulmonary Alveoli / Q000473:pathology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000517:prevention & control; D013552:Swine; D015912:Thrombolytic Therapy; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014947:Wounds and Injuries / Q000150:complications* / Q000188:drug therapy
D000933:Antifibrinolytic Agents; D010919:Placebos; D014568:Urokinase-Type Plasminogen Activator