Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism

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Abstract

Background

The experimental studies of venous thromboembolism (VTE) as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE.

Methods

Rats were allocated to the VTE (n=54) or control groups (n=9). The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis (DVT). One, four or seven-day-old thrombi were injected into the right femoral vein to induce DVT-pulmonary thromboembolism (DVT-PTE). The rats were sacrificed 1, 4 or 7 days later (Dn (1,4,7) Pn(1,4,7) subgroups (n=6)), and the lungs were examined using light and electron microscopy.

Results

On gross dissection, the rate of DVT formation was higher on day 1 (D1Pn: 100%, 18/18) than day 4 (D4Pn: 83%, 15/18; χ2=5.900, P=0.015) or day 7 (D7Pn: 44%, 8/18; χ2=13.846, P=0.000). On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D1Pn subgroup (39%, 7/18) than the D4Pn (73%, 11/15; χ2=3.915, P=0.048) and D7Pn subgroups (100%, 8/8; χ2=8.474, P=0.004); however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi.

Conclusions

This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.

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