An Experimental Model for the Study of Venous Thrombosis in Vivo

The lack of a satisfactory in vivo experimental model has probably been responsible for the delay in the clinical application of recent advances in in vitro research on thrombosis. This paper describes a model in which thrombosis is initiated by an electrical stimulus. The thrombus produced has the histological and biochemical features of human deep vein thrombosis (DVT).

The minimum stimulus necessary to induce thrombosis was first determined by passing a fixed current for timed intervals along the femoral veins of 10 rabbits. Thrombi were seen 24 hours later if the total charge passed exceeded a threshold value of 25 millicoulombes. With this small current, no endothelial changes were visible immediately after the passage of the charge on light or scanning electron microscopy. At 24 hours a mural thrombus formed, which had fully cross-linked fibrin and histological features resembling human DVT.

In the second series of experiments, the sequence of changes occurring in thrombus production was investigated in 3 groups of 18 rabbits each. After passage of the critical charge along the femoral vein in each animal, veins were removed at fixed intervals, the contralateral vein acting as a control. The veins were examined by scanning electron-microscopy (Group I), transmission electron-microscopy (Group II) and light microscopy (Group III), The earliest changes were detectable at 5 minutes and consisted of the laying down of an organised structure of criss-crossing fibrin strands with small platelet clumps at fibrin intersections. Later the fibrin structure spread towards the lumen; platelet clumps fused and a coralline thrombus was formed by 24 hours. The significance of these changes will be discussed.