Journal article

Publication year: 1999

Pages: 1566-1572

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Volume number: 19

Issue number: 6

ISSN: 1079-5642

DOI Link: https://doi.org/10.1161/01.ATV.19.6.1566

Publisher: American Heart Association

Abstract: 
The physiological inhibitor of thrombin, antithrombin III (ATIII, Kybernin P) was investigated for its antiinflammatory and anticoagulant effects in a pig model of septic shock. Pigs were infused with a dose of 0.25 mu g . kg(-1) . h(-1) of lipopolysaccharide (LPS) over a period of 3 hours. Animals developed systemic inflammation, disseminated intravascular coagulation (DIC), organ failure and cardiovascular abnormalities, namely pulmonary hypertension and systemic hypotension. Twenty septic pigs were allocated to 2 study groups, treated either with ATIII (n=10) or placebo (n=10). ATIII was administered as a 250-U/kg IV bolus infusion for 30 minutes (-60 to -30 minutes) followed by a single IV bolus of 125 U/kg (t=0) and a second 30-minute infusion of 250 U/kg (120 to 150 minutes). ATIII significantly prevented the development of a DIG; the increase in fibrin monomers (placebo, 11.4+/-9.1 reciprocal titers, at 6 hours) was completely overcome by ATIII (P<0.05). ATIII significantly prevented the increase in thromboxane (TXB2) levels, which were 809+/-287 pg/mL in the placebo and 420+/-174 pg/mL in the verum group after 6 hours (P<0.02). On the other hand, ATIII had no influence on TNF levels. In a lethal study with an increased dose of LPS (0.5 mu g . kg(-1) . h(-1)). A significant reduction in mortality was observed in the ATIII group (0 of 7) compared with the placebo group (4 of 6) (P<0.05, chi(2) test) a significant reduction of pulmonary hypertension (placebo, 42.0+/-11.1 mm Hg; ATIII, 23.6+/-7.5 mm Hg, P<0.05), but no effect on systemic hypotension, was noted in the ATIII group. It was thus concluded that modulation of the procoagulatory state by substitution of ATIII results in a late beneficial antiinflammatory effect in this model of septic shock.

Harvard Citation style: Dickneite, G. and Leithäuser, B. (1999) Influence of antithrombin III on coagulation and inflammation in porcine septic shock, Arteriosclerosis, Thrombosis, and Vascular Biology, 19(6), pp. 1566-1572. https://doi.org/10.1161/01.ATV.19.6.1566

APA Citation style: Dickneite, G., & Leithäuser, B. (1999). Influence of antithrombin III on coagulation and inflammation in porcine septic shock. Arteriosclerosis, Thrombosis, and Vascular Biology. 19(6), 1566-1572. https://doi.org/10.1161/01.ATV.19.6.1566