Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock.
Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysaccharide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFalpha levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFalpha levels, independently from the anticoagulant actions of these inhibitors.
Fourrier
F
F
Réanimation Polyvalente and Equipe de recherche JE 2084, Hôpital R. Salengro, Centre Hospitalier Régional Universitaire, Université Lille 2, France.
Jourdain
M
M
Tournoys
A
A
Gosset
P
P
Mangalaboyi
J
J
Chopin
C
C
D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D011486:Protein C / Q000032:analysis / Q000494:pharmacology*; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy*; D013552:Swine
D016207:Cytokines; D011486:Protein C; D000990:Antithrombin III; D005340:Fibrinogen; D010100:Oxygen