Experimental Model of Large Pulmonary Embolism Employing Controlled Release of Subacute Caval Thrombus in Swine

Abstract

Purpose We aimed to develop a catheter based model of large pulmonary embolism in swine based on in situ venous thrombus formation. Materials and Methods Ten Yorkshire swine underwent transjugular implantation of a retrievable inferior vena cava (IVC) filter. A thrombin and collagen mixture was injected into a confined space created by two inflated balloons proximal and distal to the IVC filter. Animals were survived for 7±3 days to allow the thrombus to organize in situ. The caval thrombus was released upon transcatheter retrieval of the IVC filter and embolized into the main and branch pulmonary arteries. The severity of pulmonary embolism was scored by digital subtraction angiography (Miller index). At necropsy thrombi were recovered and analyzed by histopathology. Results Large pulmonary embolism was induced in all animals (average Miller index score of 15±5). Two animals developed saddle embolus with bilateral pulmonary artery occlusion and five developed proximal occlusion of either the left or right pulmonary arteries. Nevertheless no animal exhibited significant hemodynamic compromise. Large tubular thrombi were explanted in the size range of 5–10 cm long and .5–1 cm wide. Histology indicated an organized thrombus with infiltration of white blood cells and fibrin deposition. Conclusions Large caval thrombi can be formed in vivo and released at a predetermined time to induce large pulmonary embolism in a large animal model. This may help developing and testing new therapeutic approaches for pulmonary embolism.

A porcine in‐vivo model of acute pulmonary embolism

“…An experimental model of a more chronic thrombus created in vivo in the inferior vena cava has been developed. 22 In this chronic model, it was, however, not possible to control the size of the thrombus, thereby creating a large variance in the model. Furthermore, the model is time-consuming and logistically challenging.…”

“…There are overall very few in vivo models of acute PE and, to our knowledge, none that fulfills all of the criteria above. 14 – 22 …”

Establishment of a canine model of acute pulmonary embolism with definite right ventricular dysfunction through introduced autologous blood clots

“…Previous studies have induced major PE in a large animal model using autologous blood clots either through in situ thrombus formation [14] or by injecting in vitro incubated clots through the jugular or femoral vein [15,20,21]. The disadvantage of the former technique is that it is difficult to control the size of the thrombus and the severity of the pulmonary artery embolization, and it is easy to cause hemodynamic collapse in the animals.…”

“…Several experiments inducing massive PE in large animal models have been reported before [13][14][15]. However, the subjects were unstable owing to the risk of hemodynamic collapse, and right ventricular function was not evaluated.…”

Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

“…There are numerous other studies that have focused on nonfatal PE and chronic thromboembolic pulmonary hypertension (CTEPH). [ 15 16 17 ] However, there are limited reports on PTE leading to CA. Furthermore, although PTE patients are known to exhibit, a marked disturbance in the stoichiometric balance between hemodynamics and respiration,[ 18 19 20 ] the mechanisms and pathophysiology of CA caused by PTE remain unclear.…”