Pulmonary Valve Conduit Research Articles

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Tissue Engineering of Pulmonary Heart Valves on Allogenic Acellular Matrix Conduits

Background —Tissue engineering using in vitro–cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. Methods and Results —Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (α-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. Conclusions —The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Pulmonary ventricular outflow reconstruction with a size-reduced cryopreserved pulmonary valve allograft: mid-term follow-up.

Surgical reduction of pulmonary allografts is being performed because of the shortage of allografts of suitable size for pediatric use. However, the outcome of size-reduced pulmonary allografts for pulmonary conduits is unknown. In the present study, cryopreserved pulmonary allografts harvested from adults at the time of kidney donation were size-reduced and used in 4 children, 2 with pulmonary atresia and ventricular septal defect and 2 with atrioventricular discordance, pulmonary atresia and ventricular septal defect. They all had undergone right and/or left modified Blalock-Taussig shunt operations with a 5-mm synthetic graft prior to the reparative operations. They underwent definitive repair with a size-reduced cryopreserved pulmonary allograft valved conduit and were followed up for 2-5 years. Postoperative echocardiographic and cineangiographic assessments revealed excellent function of the pulmonary bicuspidalized valves with a minimal pressure gradient and no, or only trivial, regurgitation. Although the long-term result of a cryopreserved bicuspid pulmonary valved conduit remains unknown, the remodeled bicuspid pulmonary allograft conduits showed excellent hemodynamic characteristics in mid-term follow-up and appear to be a reasonable alternative to other types of conduits when an appropriate-sized allograft is not available.

Use of a bovine jugular vein graft with natural valve for right ventricular outflow tract reconstruction: A one-year animal study

Objective: We evaluated a bovine jugular vein graft with a natural trileaflet valve for right ventricular outflow tract reconstruction in a canine study for an entire year. Methods: Heparinized bovine jugular vein grafts with a natural valve cross-linked with a hydrophilic polyepoxy compound of 18 to 20 mm in internal diameter were implanted in the right ventricular–pulmonary arterial position in eight dogs, and the main natural pulmonary artery was ligated. Anticoagulants were not used after implantation. Five grafts were retrieved on day 182 after implantation and the other three grafts on days 196, 375, and 385, respectively, and were inspected by macroscopic and microscopic observation. Cardiac catheterization, followed by angiography and echocardiography, was done just before graft retrieval. Results: No graft kinking or regurgitation of the valve was observed. Echocardiography showed natural valve motion without thickening of the leaflets. Blood pressure in the conduits ranged from 18/9 to 31/4 mm Hg, in the right ventricle from 18/4 to 40/0 mm Hg, and the gradient varied from 0 to 14 mm Hg. The explanted conduits maintained their original shape, softness, and pliability with good coaptation of valves, without calcification or degenerative changes, except for one leaflet with slight deformation. In microscopic observation, endothelial cells lined the luminal surface of the conduit except for the areas adjacent to the valve. Conclusion: The graft worked perfectly as a right ventricular–pulmonary arterial valved conduit without anticoagulant therapy for a long time. J Thorac Cardiovasc Surg 1997;114:224-33

Balloon expandable stent implantation in stenotic right heart valved conduits

Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model was used, in which the pulmonary artery was ligated and a right ventricular to pulmonary artery 14 mm bioprosthetic Dacron valved conduit implanted.In five baboons, at an average of 40 months after valved conduit implantation, fibrointimal stenosis at the valve site resulted in narrowing and a mean transconduit pressure gradient of 49 mm Hg (range 33 to 65). A tubular slotted steel stent (1.2 cm long) was deployed within the valved conduit after inflation of an 8 to 15 mm diameter balloon catheter that was introduced through the femoral vein. A stent was delivered to all valved conduits; however, in two baboons, balloon undersizing resulted in stent dislodgment. In the remaining three baboons, the transconduit gradient was reduced by 59% (49 to 20 mm Hg) and right ventricular systolic pressure decreased acutely by 35% (77 to 50 mm Hg).It is concluded that stent deployment is feasible in right ventricular to pulmonary artery stenotic valved conduits and may result in significant hemodynamic improvement. However, successful stent delivery is critically dependent on the proper selection of stent length and balloon diameter.

Doppler evaluation of homograft valved conduits in children

To assess the flow characteristics of homograft valved conduits in the immediate postoperative period, 69 children with 71 homograft conduits underwent 2-dimensional and Doppler echocardiographic examination at 1 to 40 days (mean 8) after surgery. Of the 71 conduits studied, 19 were aortic and 52 were pulmonary homograft valved conduits. Two aortic homograft valved conduits were inserted in the aortic position, whereas all remaining homografts were placed in the pulmonary position. On the immediate postoperative echocardiogram, 25 (35%) of the conduit valves had no regurgitation and 44 (62%) had 1+ (mild) regurgitation. Two pulmonary valved conduits (3%) in the pulmonary position had 2+ (moderate) regurgitation and right ventricular dimensions >95% for body surface area. The peak velocity across the homograft valve was normal (<1.3 m/s) in 58 valves (82%). In the remaining 13 valves, peak velocity ranged from 1.4 to 2.6 m/s. No homograft valve had a peak velocity >2.6 m/s in the immediate postoperative period. To assess the fate of homograft valved conduits in the intermediate-term follow-up period, 38 children with 38 conduits had a repeat echocardiogram at 6 to 25 months (mean 15 ± 6) after surgery. Of the 38 conduits examined, 10 (26%) had no regurgitation, 25 (66%) had 1+ regurgitation and 3 (8%) had 2+ regurgitation. Progression of the amount of regurgitation occurred in 11 (29%) patients. At the follow-up examination, peak velocity was ≤1.4 m/s across 34 conduit valves, between 1.4 and 2.6 m/s across 3 valves and >2.6 m/s across 1 valve. This latter patient had a 3.2-m/s jet across the proximal insertion of the conduit and no further increase across the valve itself. Thus, no patient had evidence of conduit valve stenosis. Of the 38 patients, 9 had Doppler evidence of obstruction at the conduit insertion (8 at the distal end and 1 with the aforementioned proximal obstruction). Most obstructions were of mild to moderate severity and only 2 patients (5%) had severe conduit stenosis. Thus, in the immediate postoperative period, normally functioning homograft valved conduits frequently have mild regurgitation (62%) and rarely have moderate or severe regurgitation (3%), with peak velocities reaching <2.6 m/s. In the inpatients, 9 had Doppler evidence of obstruction at the conduit insertion (8 at the distal end and 1 with the aforementioned proximal obstruction). Most obstructions were of mild to moderate severity and only 2 patients (5%) had severe conduit stenosis. Thus, in the immediate postoperative period, normally functioning homograft valved conduits frequently have mild regurgitation (62%) and rarely have moderate or severe regurgitation (3%), with peak velocities reaching <2.6 m/s. In the intermediate follow-up period, homograft valved conduits may develop an additional degree of regurgitation (29%), frequently continue to have conduit peak velocities <2.6 m/s (97%) and uncommonly develop hemodynamically significant obstruction, usually at the ends of the conduit (5%).