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 th e coagulation cascade and might regulate the cytokine network. We test ed the possibility that a combined supplementation using these two inh ibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation paramet ers, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli end otoxin (lipopolysaccharide). Four groups were studied: control lipopol ysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same dose s). The endotoxin infusion resulted in a typical hypokinetic shock wit h disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressur e 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 TNF alpha 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 t he ATIII-PC group. We conclude that in this acute endotoxic model, a c ombined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNF alpha levels, independently from the anticoagulant actions of these inhibitors.