Activity and transport of antithrombin during acute limb ischemia.
Antithrombin (AT III), a major circulating anticoagulant, may be influenced by ischemia-induced changes in microvascular integrity and contribute to localized hypercoagulability. In a nonheparinized intact canine hindlimb model we determined AT III activity by chromogenic substrate assay (S-2238); coagulation changes with fibrinogen, activated partial thromboplastin time (aPTT), and prothrombin time (PT); and transvascular exchange by lymph-to-plasma total protein concentration ratio. Femoral venous plasma and lymph samples were assayed during 1 hour of steady state (C), 6 or 8 hours of aortoiliac occlusion (I), and 1 or 3 hours of reperfusion (R). Four groups were studied: GI, sham operated (n = 5); GII, moderate ischemia (n = 7), arterial pressure 30% to 45% C, GIII, 6 hours of severe ischemia (n = 7), arterial pressure 5% to 20% C; and GIV, 8 hours of severe ischemia (n = 5), arterial pressure 5% to 20% C. All parameters varied near baseline in the control group and the group with moderate ischemia. Fibrinogen decreased after 3 hours of ischemia in GIII from 218 +/- 38 to 175 +/- 46 mg/dl (mean +/- SEM) and in GIV from 254 +/- 39 to 201 +/- 44 mg/dl (p less than 0.005) as aPTT and PT increased. All parameters returned to baseline on R in GIII only. Plasma AT III decreased in GIV from 89% +/- 4.6% to 53.6% +/- 16.2% (p less than 0.005) after 3 hours and remained low during late I and R.(ABSTRACT TRUNCATED AT 250 WORDS)
Burke
P E
PE
St. Vincent's Hospital, Dublin, Ireland Republic.
Harvey
C F
CF
Phythian
C L
CL
Gervin
C A
CA
Greenfield
L J
LJ
D000208:Acute Disease; D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000378:metabolism*; D001692:Biological Transport; D001777:Blood Coagulation; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000097:blood*; D008196:Lymph / Q000032:analysis / Q000378:metabolism; D008297:Male; D013997:Time Factors
D001798:Blood Proteins; D000990:Antithrombin III