Quantifying the effect of locally delivered anticoagulant drugs: modification of an in vivo model of venous thrombosis.
Increasingly, attention is focusing on the local delivery of antiplatelet and fibrinolytic therapy as a means of preventing intravascular thrombosis. A simple, reproducible model of thrombosis, based upon vascular damage is needed to test these agents in vivo. We have therefore modified a rat vena cava model of venous thrombosis based upon vascular injury and stasis. Wistar rats are anaesthetised, the inferior cava dissected free and a segment isolated by slings distally above the iliacs and proximally above the left renal vein. All other tributaries are ligated. Vascular injury is induced by externally applying soft-jaw clamps for 5 min. Agents to be tested are introduced into the isolated segment via a left renal vein cannula left in situ for 15 min and then flushed from the cava. Blood is allowed to refill the segment, all remaining slings are tied and the animal left for 30 min before being killed. The cava is then opened and thrombus removed and weighed. Scanning electron microscopy of the cava after clamping shows areas of normal endothelium interspersed with areas of denuded endothelium and exposed subendothelial connective tissue. Histological and immunohistochemical staining indicates the thrombus is composed of red cells, platelets and fibrin. The model was validated by assessing the effects of 2 different doses of locally delivered tissue-type plasminogen activator (tPA). The mean weights of thrombus were [mg (SD)]: Control (saline; n = 8) 39.0 (8.73), tPA 0.01 mg/ml (n = 6) 45.5 (10.56) and tPA 1 mg/ml (n = 8) 3.5 (3.4). Comparing 1 mg/ml tPA vs. 0.01 mg tPA vs. control, p < 0.001 (Mann-Whitney test).(ABSTRACT TRUNCATED AT 250 WORDS)
Underwood
M J
MJ
Academic Department of Cardiology, Glenfield General Hospital, Leicester, UK.
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R
R
Gershlick
A H
AH
de Bono
D P
DP
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D003250:Constriction; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000188:drug therapy* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use; D014682:Vena Cava, Inferior / Q000473:pathology
D000925:Anticoagulants; D010959:Tissue Plasminogen Activator