Preliminary report of a thoracic duct-to-pulmonary vein lymphovenous anastomosis in swine: A novel technique and potential treatment for lymphatic failure

Abstract

Objective: The thoracic duct is the largest lymphatic vessel in the body, and carries fluid and nutrients absorbed in abdominal organs to the central venous circulation. Thoracic duct obstruction can cause significant failure of the lymphatic circulation (i.e., protein-losing enteropathy, plastic bronchitis, etc.). Surgical anastomosis between the thoracic duct and central venous circulation has been used to treat thoracic duct obstruction but cannot provide lymphatic decompression in patients with superior vena cava obstruction or chronically elevated central venous pressures (e.g., right heart failure, single ventricle physiology, etc.). Therefore, this preclinical feasibility study sought to develop a novel and optimal surgical technique for creating a thoracic duct-to-pulmonary vein lymphovenous anastomosis (LVA) in swine that could remain patent and preserve unidirectional lymphatic fluid flow into the systemic venous circulation to provide therapeutic decompression of the lymphatic circulation even at high central venous pressures.

Methods: A thoracic duct-to-pulmonary vein LVA was attempted in 10 piglets (median age 80 [IQR 80-83] days; weight 22.5 [IQR 21.4-26.8] kg). After a right thoracotomy, the thoracic duct was mobilized, transected, and anastomosed to the right inferior pulmonary vein. Animals were systemically anticoagulated on post-operative day 1. Lymphangiography was used to evaluate LVA patency up to post-operative day 7.

Results: A thoracic duct-to-pulmonary vein LVA was successfully completed in 8/10 (80.0%) piglets, of which 6/8 (75.0%) survived to the intended study endpoint without any complication (median 6 [IQR 4-7] days). Initially, 2/10 (20.0%) LVAs were aborted intraoperatively, and 2/10 (20.0%) animals were euthanized early due to post-operative complications. However, using an optimized surgical technique, the success rate for creating a thoracic duct-to-pulmonary vein LVA in six animals was 100%, all of which survived to their intended study endpoint without any complications (median 6 [IQR 4-7] days). LVAs remained patent for up to seven days.

Conclusion: A thoracic duct-to-pulmonary vein LVA can be completed safely and remain patent for at least one week with systemic anticoagulation, which provides an important proof-of-concept that this novel intervention could effectively offload the lymphatic circulation in patients with lymphatic failure and elevated central venous pressures.

Keywords: Congenital heart disease; Fontan procedure; Lymphatic failure; Lymphatic flow disorder; Lympho-venous anastomosis; Lymphovenous anastomosis.

Figure 1:

Thoracic Duct and Pulmonary Vein Dissection. A) After a right thoracotomy, the thoracic duct is dissected from the level of the right inferior pulmonary vein to the diaphragm using electrocautery. All adventitia surrounding the thoracic duct should be preserved to maintain its integrity for LVA creation. B) The right pulmonary vein is mobilized circumferentially and dissected towards the lung parenchyma, which reduces the likelihood of LVA kinking once the lung is reinflated. Once heparin is administered and allowed to circulate, the pulmonary vein is clamped while keeping its posterior wall exposed at the site of the intended thoracic duct-to-pulmonary vein LVA. Ao: aorta; Es: esophagus; LN: lymph node; PV: area of dissection for exposing the right inferior pulmonary vein; VC: vertebral column.

Figure 2:

Right Inferior Pulmonary Venotomy and Preparing the Thoracic Duct Conduit. A) With a side-biting clamp applied to the right inferior pulmonary vein, a small stab incision is made with a scalpel and the venotomy is extended 4–5 mm along the length of the pulmonary vein with scissors (arrow). The venotomy is widened by excising a small piece of tissue (1 mm) to provide a larger stoma at the site of the intended thoracic duct-to-pulmonary vein LVA. B) The mobilized thoracic duct is transected near the level of the right inferior pulmonary vein, and its free lumen end is beveled at a 45-degree angle and incised caudally to create a hood that is equal in size to the venotomy (arrow).

Figure 3:

Legend-Sizing the Thoracic Duct for Creation of the Lymphovenous Anastomosis. A) After dissecting, mobilizing, and transecting the thoracic duct near the level of the right inferior pulmonary vein, it must be sized appropriately to reduce slack and minimize the risk of kinking once the lymphovenous anastomosis is completed and the lung is reinflated. B) The thoracic duct should be straightened and measured precisely so that it will meet the pulmonary vein with minimal tension. Ao: aorta; Az: azygous vein; Pl: pleura; TD: thoracic duct.

Figure 4:

Creation of a Thoracic Duct-to-Pulmonary Vein Lymphovenous Anastomosis. A) The thoracic duct-to-pulmonary vein LVA is created by direct anastomosis between the thoracic duct and the posterior aspect of the right inferior pulmonary vein using an end-to-side technique and either a single running suture (8–0 polypropylene) or multiple interrupted sutures (9–0 nylon) under a high-powered surgical microscope (Leica Microsystems, Wetzlar, Germany). The first stitch is placed at the apex of the venotomy, and suturing continues clockwise along the posterior wall of the pulmonary vein until the LVA is completed. B) After the LVA is completed and clamps are removed from the thoracic duct and pulmonary vein, clear lymphatic fluid should be seen freely flowing through the thoracic duct and into the pulmonary vein (thin arrows). C) A small amount blood is expected to regurgitate into the thoracic duct from the pulmonary vein (thick arrow) with positive-pressure ventilation and atrial contractions since the newly established lymphovenous junction lacks an outlet valve that is normally present near the native confluence between the thoracic duct and innominate vein. PV: right inferior pulmonary vein; TD: thoracic duct.

Figure 5:

Thoracic Duct-to-Pulmonary Vein Lymphovenous Anastomosis with Unobstructed Lymphatic Fluid Flow. A) Thoracic duct-to-pulmonary vein LVA (arrow) patency was confirmed by lymphangiography up to post-operative day 7. B) Digital subtraction imaging provides better visualization of contrast flowing unobstructed through the LVA and being briskly washed away with pulmonary blood flow into the systemic circulation.

Figure 6:

Post-Operative Complications After Thoracic Duct-to-Pulmonary Vein Lymphovenous Anastomosis. A-B) The first animal that had a thoracic duct-to-pulmonary vein LVA completed did not receive post-operative systemic anticoagulation. The animal initially recovered well but became acutely ataxic on POD 4 and was euthanized due to concerns about a stroke. Necropsy revealed a large mobile thrombus (arrow) within the LVA that extended into the right inferior pulmonary vein. All subsequent animals were systemically anticoagulated beginning on POD 1, and there were no further thromboembolic complications. C-D) The second LVA that was completed utilized an end-to-end technique with a small pulmonary vein. The animal was extubated and recovered well in the immediate post-operative period but developed hemoptysis on POD 1 and was euthanized due to concerns for pulmonary hemorrhage. Necropsy revealed a large area of congestion and necrosis in the right lower lobe that was not compatible with survival. As a result, all future LVAs were created using an end-to-side technique to ensure that pulmonary vein blood flow was not jeopardized, and there were no further post-operative complications.