Objective: To observe the changes of thrombi and vessel intima in a rat model of venous thromboembolism (VTE).
Methods: Seventy-eight SD rats were randomly divided into deep vein thrombosis (DVT) group (n = 18), deep vein thrombosis-pulmonary thromboembolism (DVT-PTE) group (n = 54) and control group (n = 6). Rats in DVT and DVT-PTE groups were undergoing local blocking of left femoral artery with micro vessel clip to cause DVT. One, 4, and 7 days later 6 rats from DVT group were killed with their femoral veins observed by light and electron microscopy. Rats in DVT-PTE group underwent injection of the thrombi from left femoral vein solution in normal saline into the right femoral vein 1, 4, and 7 days after DVT formation to establish model of DVT-PTE. The 6 rats of each subgroup [D(n (1, 4, 7))P(n (1, 4, 7)) subgroups] were killed 1, 4, and 7 days after DVT-PTE formation respectively with their lungs observed by light and electron microscopy.
Results: (1) On day 1 after DVT, the successful rate of DVT was 100%. The positive thrombus rate in femoral veins on gross is lower on day 7 after DVT [42% (10/24)] than that on day 1 after DVT (chi(2) = 19.765, P < 0.01). The successful rates of DVT-PTE model were 100% (18/18), 83% (15/18), 44% (8/18) in the D(1)P(n), D(4)P(n) and D(7)P(n) subgroups respectively. The successful rate of DVT-PTE model is lower in the D(7)P(n) subgroups than that in the D(1)P(n) (chi(2) = 13.846, P < 0.01) and D(4)P(n) (chi(2) = 5.900, P < 0.05) subgroups. (2) One, 4, and 7 days after DVT, there were reddish, mixed, and organized thrombi in femoral veins. The thrombi in pulmonary arteries caused by the 4 or 7 days thrombi of DVT showed lower dissolubility than that from one day thrombi of DVT. The positive thrombus rate in pulmonary arteries on gross is higher in the D(4)P(n) and D(7)P(n) subgroups [73% (11/15) and 100% (8/8)] than that in the D(1)P(n) subgroups [39% (7/18, chi(2) = 3.915, P < 0.05; chi(2) = 8.474, P < 0.01)]. The ratio of vessel wall area and total vessel increased in D(1)P(7), D(4)P(4), D(7)P(4) and D(7)P(7) subgroups compared to the control group (P = 0.03, 0.00, 0.00, 0.011, respectively). (3) The junctures of femoral venous endothelial cells were ruptured and the intra-elastic layers were exposed on the 1(st) day, then the endothelial cells and intra-elastic layers became to disappear on the 7(th) day. The hyperplasia of pulmonary arterial intimal were observed on the 4(th) or the 7(th) day after the thrombi in pulmonary arteries caused by the 1 or 4 days thrombi of DVT. However, pulmonary arterial endothelial cells and intra-elastic layers maybe disappear on the 1(st) day after the thrombi in pulmonary arteries caused by the 7 days thrombi of DVT.
Conclusions: The age and nature of thrombi before the embolization are related to the outcome of emboli and pulmonary arterial intimal alterations. For intimal, there are the changes of hyperplasia, intra-elastic layers thickening and even disappearance in femoral veins and pulmonary arteries after VTE.