Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock.
In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to evaluate the effect of a continuous infusion of live serogroup A streptococci (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony-forming units/kg per h] caused early signs of severe septicaemia in the pigs, with pulmonary hypertension, systemic hypotension, reduced cardiac output and liver hypoperfusion, ultimately leading to shock with a high mortality. There was a sequential and ordered activation of the coagulation, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold increase at 4 h). These findings are similar to changes observed during endotoxin infusion. This procoagulant state favours disseminated intravascular coagulation and microthrombus formation, ultimately threatening tissue viability.
Department of Surgery, Institute for Experimental Medical Research, Ullevaal University Hospital, Oslo, Norway. torunn.satre@ioks.uio.no
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Saetre
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Lindgaard
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Lyberg
D000818:Animals; D000990:Antithrombin III; D001777:Blood Coagulation; D002302:Cardiac Output; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D005342:Fibrinolysis; D006976:Hypertension, Pulmonary / Q000382:microbiology; D007022:Hypotension / Q000382:microbiology; D008099:Liver / Q000098:blood supply; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012703:Serotyping; D012772:Shock, Septic / Q000097:blood*; D013290:Streptococcal Infections / Q000097:blood* / Q000473:pathology; D013297:Streptococcus pyogenes / Q000145:classification / Q000302:isolation & purification; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator