thromboplastin and Endocarditis

High-altitude hypoxia causes a hypercoagulable state. In our previous study on the blood coagulation system in rats, nonbacterial thrombotic endocarditis (NBTE) developed after 4-12 weeks' exposure to the equivalent of 5500 m in altitude. We hypothesized that TF (tissue factor)-producing cells in the cardiac valves might be induced by the hypobaric hypoxic environment (HHE) and then trigger NBTE. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-12 weeks. We measured TF activity in the plasma and studied morphological changes in the mitral valves using immunohistochemical and immunoelectrical methods for TF protein and in situ hybridization for TF mRNA. After 4 weeks or more of exposure to HHE, 28 of the 56 surviving rats had developed NBTE. After 4-8 weeks' exposure to HHE, the plasma TF activity level was significantly higher than in control rats. There was a significant correlation between plasma TF activity and the incidence of NBTE. After 1 weeks' exposure to HHE, immunoreactivity for TF protein was detected in foamy macrophages and stromal cells in the cardiac valves. In rats with NBTE, TF protein was present in foamy macrophages and spindle stromal cells and focally present in the extracellular matrix. TF mRNA was detected in some foamy macrophages within the thrombus, TF protein was localized to the rough endoplasmic reticulum and plasma membrane of many macrophages, some fibroblasts, and a few endocardial cells. TF is associated with the pathogenesis of the NBTE induced by exposure to HHE. The accumulation of TF-producing macrophages during exposure to HHE may be responsible for initiating thrombus formation.

Topics: Animals; Atmosphere Exposure Chambers; Atmospheric Pressure; Endocarditis; Hypoxia; Immunoenzyme Techniques; In Situ Hybridization; Male; Microscopy, Immunoelectron; Mitral Valve; Myocardium; Rats; Rats, Wistar; RNA, Messenger; Thromboplastin; Thrombosis

In vitro infection of cultured human cardiac valve endothelium (HCVE) with Staphylococcus aureus was used as a model to study potential mechanisms of vegetation formation in infective endocarditis. S. aureus was observed to adhere to and be ingested by HCVE. Infection for 8 h resulted in increased levels of procoagulant activity in HCVE, shown to be tissue factor by a specific assay. Mean activity in infected HCVE was 662 +/- 149 (mU/10(5) HCVE +/- 1 SD) versus 221 +/- 78 in control HCVE; surface-expressed activity was 57 +/- 25 in infected monolayers and undetectable (less than or equal to 10) in controls. Bacteria alone had no activity. These results suggest that endothelium may have a functional role in the pathogenesis of S. aureus endocarditis and may provide one potential mechanism for activating coagulation to initiate vegetation formation on a colonized cardiac valve.

Topics: Cell Survival; Culture Techniques; Endocarditis; Endothelium; Heart Valves; Humans; Microscopy, Electron; Staphylococcal Infections; Thromboplastin; Time Factors

Topics: Aged; Aortic Valve; Disseminated Intravascular Coagulation; Endocarditis; Hernia, Inguinal; Humans; Hyaline Membrane Disease; Infant, Newborn; Intestine, Small; Kidney; Lung; Male; Postoperative Complications; Shwartzman Phenomenon; Thromboplastin