No interplay between the pathways mediating coagulation and inflammation in tissue factor-induced disseminated intravascular coagulation in rats.
OBJECTIVE
Previous reports have suggested an interplay between the pathways mediating coagulation and inflammation in endotoxemia and sepsis. The present study was designed to examine whether cross-signaling between the pathways mediating coagulation and inflammation occurs, as suggested by the pattern of cytokine production observed following tissue-factor (TF)-induced disseminated intravascular coagulation (DIC).


METHODS
Prospective, comparative, experimental study.


METHODS
Laboratory at a university hospital.


METHODS
Male Wistar rats, aged 6-7 wks, and weighing 160-170 g.


METHODS
Male Wistar rats were administered TF (3.75 units/kg every 4 hrs), TF, and tranexamic acid (TA; 50 mg/kg every 4.5 hrs) or lipopolysaccharide (30 mg/kg every 4 hrs) via the tail vein, and blood was sampled at 0, 4, 8 and 12 hrs.


RESULTS
Subsequent alterations in thrombin-antithrombin complex and fibrinogen levels, as well as platelet counts, indicated that the severity of both types of experimental DIC (TF-induced and lipopolysaccharide-induced) was similar with respect to hemostatic activation and development of consumption coagulopathy. In lipopolysaccharide-induced DIC, a sharp increase in plasma tumor necrosis factor levels was observed at 4 hrs, after which a sharp decline was noted. Plasma levels of interleukin-6 were markedly increased at 4 hrs, after which a sustained elevation was observed for the duration of the experimental period (tumor necrosis factor, 1270 +/- 280, 180 +/- 40, and 120 +/- 30 pg/mL at 4, 8 and 12 hrs, respectively; interleukin-6, 5810 +/- 1320, 4850 +/- 730, and 5230 +/- 1280 pg/mL at 4, 8 and 12 hrs, respectively). On the other hand, tumor necrosis factor and interleukin-6 were not detected following TF-induced DIC (0 +/- 0 at 4, 8, and 12 hrs for both tumor necrosis factor and interleukin-6). In the TF+TA group, significant increases in tumor necrosis factor and interleukin-6 were observed, compared with the TF group.


CONCLUSIONS
There is no overt interplay between the pathways mediating coagulation and inflammation in TF-induced DIC, as observed in lipopolysaccharide-induced DIC.
Ontachi
Yasuo
Y
Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan.
Asakura
Hidesaku
H
Takahashi
Yoko
Y
Hayashi
Tomoe
T
Arahata
Masahisa
M
Kadohira
Yasuko
Y
Maekawa
Mio
M
Omote
Mika
M
Yoshida
Tomotaka
T
Yamazaki
Masahide
M
Morishita
Eriko
E
Miyamoto
Ken-ichi
K
Nakao
Shinji
S
D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000503:physiopathology*; D006490:Hemostatics / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000933:Antifibrinolytic Agents; D016207:Cytokines; D006490:Hemostatics; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014148:Tranexamic Acid; D013925:Thromboplastin