| Abstract | One of the aims of research in the area of thrombosis has been to design an effective anticoagulant that would function in a predictable and direct manner. In evaluating the role of coagulation in sepsis we used factor Xa blocked in the active center with [5-(dimethylamino)1-naphthalenesulfonyl]-glutamylglycylarginyl+ ++ chloromethyl ketone (DEGR-Xa). We infused 1 mg/kg of DEGR-Xa together with LD100 concentrations of Escherichia coli (4 x 10(10) organisms/kg) into five baboons. As controls, we infused E coli alone into five baboons. The inflammatory, coagulant, and cell injury responses to E coli of both the treated and control groups were lethal and were similar in every respect except for the complete inhibition of the consumption of fibrinogen in the DEGR-Xa group. The half life of DEGR-Xa was approximately 10 hours and 2 hours, as determined by isotopic and enzyme-linked immunosorbent assays, respectively. These results for the first time demonstrate that, although coagulation occurs in E coli sepsis, fibrin formation per se did not influence the lethal outcome in this model. These results also show the effectiveness of DEGR-Xa as an anticoagulant and raise the possibility that it could serve as an alternative to anticoagulants currently in use. |
| Authors | F B Taylor Jr, A C Chang, G T Peer, T Mather, K Blick, R Catlett, M S Lockhart, C T Esmon
(Affiliation: Cardiovascular Biology Research, Oklahoma Medical Research Foundation, Oklahoma City 73104.)
|
| Journal | Blood
(Blood)
Vol. 78
Issue 2
Pg. 364-8
(Jul 15 1991)
ISSN: 0006-4971 UNITED STATES |
| PMID | 2070073
(Publication Type: In Vitro, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Amino Acid Chloromethyl Ketones
- Dansyl Compounds
- Tumor Necrosis Factor-alpha
- dansylglutamyl-glycyl-arginine chloromethyl ketone
- Factor Xa
|
| Topics |
- Amino Acid Chloromethyl Ketones
(administration & dosage, chemical synthesis, therapeutic use)
- Animals
- Blood Coagulation
- Blood Pressure
- Cattle
- Dansyl Compounds
- Disseminated Intravascular Coagulation
(prevention & control)
- Escherichia coli Infections
(complications, physiopathology)
- Factor Xa
(administration & dosage, chemical synthesis, therapeutic use)
- Female
- Heart Rate
- Humans
- Infusions, Intravenous
- Male
- Papio
- Platelet Count
- Shock
(prevention & control)
- Tumor Necrosis Factor-alpha
(analysis)
|
