Animal model of acute deep vein thrombosis

To develop an animal model of acute deep vein thrombosis (DVT).

In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n = 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n = 3), or at 100 U/min (n = 3). Saline was administered in the opposite leg. After the animals were killed, the mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min.

All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p = 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1. 32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens.

Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution.