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Hemodynamic changes and systemic activation of coagulation and fibrinolysis during controlled endotoxemia in pigs.
- Source :
-
Thrombosis research [Thromb Res] 2000 Jun 15; Vol. 98 (6), pp. 517-29. - Publication Year :
- 2000
-
Abstract
- In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.
- Subjects :
- Animals
Antifibrinolytic Agents metabolism
Blood Coagulation Factors drug effects
Blood Coagulation Factors metabolism
Blood Pressure drug effects
Cardiac Output drug effects
Endotoxemia metabolism
Endotoxins administration & dosage
Endotoxins pharmacology
Leukocyte Count drug effects
Platelet Count drug effects
Swine
Vascular Resistance drug effects
Blood Coagulation drug effects
Endotoxemia physiopathology
Fibrinolysis drug effects
Hemodynamics drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0049-3848
- Volume :
- 98
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Thrombosis research
- Publication Type :
- Academic Journal
- Accession number :
- 10899351
- Full Text :
- https://doi.org/10.1016/s0049-3848(00)00189-4