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.
Saetre
T
T
Department of Surgery, Institute for Experimental Medical Research, Ullevaal University Hospital, Oslo, Norway. torunn.satre@ioks.uio.no
Lindgaard
A K
AK
Lyberg
T
T
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