title: Pulmonary endothelial injury and altered fibrinolysis after femur fracture in rabbits.
abstract: The pathophysiology of acute lung injury after long bone fracture may be associated with endothelial damage and altered fibrinolysis. Accordingly, we studied metabolic functions of pulmonary endothelial cells: 5-hydroxytryptamine (5-HT) uptake and angiotensin-converting enzyme (ACE) activity in anesthetized rabbits before and every 4 h after long bone fracture (n = 12) or sham (n = 6). To assess changes in fibrinolysis, we studied levels of plasminogen activator inhibitor (PAI), an inhibitor of the fibrinolytic cascade. All animals in the control group and only 6 of 12 animals in the long bone fracture group survived 12 h. 5-HT uptake was depressed after 8 h in both groups. By 12 h, however, 5-HT uptake in the long bone fracture group remained depressed, but returned to baseline in the control group. Conversely, ACE activity was unchanged in both groups. PAI levels were increased in both groups at 4 h. During the next 8 h, levels in the long bone fracture group continued to increase and remained elevated, whereas levels in the control group decreased and were not greater than baseline at 12 h. Initial PAI and 5-HT uptake changes may be related to surgical preparation of the rabbit. Prolonged depression of 5-HT uptake suggests that musculoskeletal trauma is associated with pulmonary endothelial damage. Finally, impaired fibrinolysis due to increased PAI may contribute to the pathogenesis of endothelial injury after long bone fracture.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh, Pennsylvania.
authors.forename: J J
authors.initials: JJ
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Moalli
authors.forename: C
authors.initials: C
authors.lastname: Calista
authors.forename: J H
authors.initials: JH
authors.lastname: Herndon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism / Q000503:physiopathology; D005264:Femoral Fractures / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005342:Fibrinolysis; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000097:blood; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000378:metabolism / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism
chemical_list: D015849:Plasminogen Inactivators; D012701:Serotonin; D007703:Peptidyl-Dipeptidase A