Inflammatory and procoagulant mediator interactions in an experimental baboon model of venous thrombosis.
Theoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 micrograms/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP-1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Wakefield
T W
TW
Jobst Research Laboratories, Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0329.
Greenfield
L J
LJ
Rolfe
M W
MW
DeLucia
A
A
Strieter
R M
RM
Abrams
G D
GD
Kunkel
S L
SL
Esmon
C T
CT
Wrobleski
S K
SK
Kadell
A M
AM
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001772:Blood Cell Count; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D010215:Papio; D010447:Peptide Hydrolases / Q000378:metabolism; D011486:Protein C / Q000037:antagonists & inhibitors; D013924:Thrombophlebitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D015850:Interleukin-6; D016209:Interleukin-8; D011486:Protein C; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases