A Preliminary Study On The Correlation Between Two Forms Of Iliac Vein Occlusion And Venous Thrombosis

Objective: 1. To explore the technical feasibility and reproducibility of establishing swine models of iliac vein occlusion(IVO) by use of two different ligation fashions.. 2. To evaluate the correlation between two forms of IVO and thrombosis in pursuit of better understanding of the mechanisms and pathogenesis for spontaneous thrombosis secondary to IVO.Methods: Twelve miniature swine were included in the study(six male, six female; age 16–20 weeks; weight 15–20 kg), and were randomly divided into two groups, each comprising six subjects: Group A and Group B. Each animal was placed in a supine position on a digital subtraction angiography(DSA) table followed by a sheath and catheter insertion into the left femoral vein, and a venogram was performed to visualize the iliac vein and inferior vena cava(IVC). The left low abdomen was incised, and the IVC and left CIV and EIV were carefully exposed and isolated. In Group A, the proximal end of the left CIV was ligated with 4–0 silk to model CIV occlusion(CIVO). For subjects in Group B, both the left CIV and EIV were ligated together with 4–0 silk to model CIV and EIV occlusion(CEIVO). The ligature sites were at the proximal end of left CIV and EIV. Finally, a venogram was repeated to confirm that the iliac vein(s) was occluded; the abdomen was closed, and the skin wassutured with 4–0 silk. During the ligation procedure, an invasive EIV blood pressure was measured before and after ligation of the iliac vein to calculate the pressure gradient across the occlusion. A venogram was repeated 7 and 14 days postoperatively for evaluating the angiographic details with respect to the occlusive segments, collateral vessels formation, blood flow reflux as well as evidences of thrombosis. Three animals per group were euthanised at 7 and 14 days after ligation. The left CIV and EIV were isolated and immediately fixed in formalin, and the venous tissue cross-sections(5μm) were stained with haematoxylin and eosin(H&E) routinely. Data are presented as the range(mean ± standard error of the mean). Intra-and inter-group comparisons of the venous blood pressure and pressure gradient across the occlusion were performed using the paired- or independent samples T test. X2 test or fisher exact test was used for comparison of the category variables between two groups, A value of P<0.05 was considered statistically significant.Results: 1. The technical success rate of the model was 100% in both groups. None of the animals died or experienced any procedure-related complications such as major haemorrhage or infection during the study period. 2. Angiographic results: Group A:The intraoperative venogram performed immediately after ligation showed complete occlusion of the left CIV. The dynamic venography demonstrated reflux within the EIV flowing into the IVC through the internal iliac vein(IIV)and ascending lumbar vein(ALV). The repeat venograms at 7 and 14 days revealed left CIV occlusion with well-developed collateral vasculature including the pelvic vein plexus and inferior epigastric vein. No signs of thrombosis were observed. Group B:The intraoperative venogram performed immediately after ligation showed complete occlusion of the left CIV and EIV. The IIV and ALV were not visible, and bloodstasis was observed within the EIV without drainage through collateral networks. At 7 days, the venogram revealed a filling defect in the EIV and femoral vein(FV) consistent with thrombosis. At 14 days, the EIV and FV were completely occluded in two subjects and partially occluded in one subject, indicating thrombus propagation. Group B: The invasive CIV blood pressure was 5-7mm Hg(6±0.49 mm Hg). The invasive EIV blood pressure before and after ligation was 6-8 mm Hg(7 ± 0.89 mm Hg) and 25-30 mm Hg(27 ±1.79 mm Hg), respectively. Before ligation, the pressure gradient between IVC and EIV was 0–1 mm Hg(0.80 ±0.25 mm Hg). After ligation, the pressure gradient across the occlusion was 20–23mm Hg(22±2.09 mm Hg), indicating a significant increase after ligation(P=0.000). Group B: The invasive CIV blood pressure was 5–7mm Hg(6 ±0.58 mm Hg). The invasive EIV blood pressure before and after ligation was 5–8 mm Hg(7.17±1.17 mm Hg) and 55–64 mm Hg(60.17±3.96 mm Hg), respectively. Before ligation, the pressure gradient between IVC and EIV was 0–1 mm Hg(0.75 ±0.27 mm Hg). After ligation, the pressure gradient across the occlusion was 50-59 mm Hg(55.36 ±1.89 mm Hg), indicating a significant increase(P=0.000). Additionally, the pressure gradient across the occlusion was significantly higher in Group B than in Group A(P=0.000). No difference was observed between the two groups in the invasive EIV blood pressure before ligation(P = 0.695). 3. Pathological examinations Group A: none of the animals showed intraluminal thrombosis. The venous endothelium was smooth without any leukocyte infiltration within vein wall. In Group B: intraluminal thrombosis was observed in all animals and was firmly adhered to the venous endothelium at 7 days. At 14 days, a moderately organized thrombus was observed. The venous endothelium and wall were thickened and showed severe lymphocytic infiltration. The changes were more apparent and severeat 14 days compared with those at 7 days.Conclusion: 1. The ligation of CIV alone or in combination of EIV ligation to create IVO model is technically safe. The two IVO models may differ significantly with respect to occlusive segment, collateral networks, as well as downstream thrombosis. 2. The CEIVO model had a higher prevalence of thrombosis than the CIVO model. This CEIVO model produces comparatively less collateral drainage, higher intra-venous pressure and greater inflammation that can contribute to the thrombosis prone to this type of model.