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Background: The ideal scaffold material for tissue engineered heart valves is discussed controversially. We evaluated acellularized xenogenic matrix constructs with and without seeding with autologous vascular cells in the pulmonary circulation in a sheep model., Methods: Porcine pulmonary valve conduits (n=16) were acellularized by trypsin/ EDTA incubation. Autologous myofibroblasts and endothelial cells were harvested from carotid arteries; xenogenic valve conduits (n=10) were repopulated with these autologous cells resulting in uniform cellular restitution of the pulmonary valve conduit surface. Using this method, we implanted autologous cell/xenogenic matrix constructs (XB) in ten animals. In six control animals acellularized/xenogenic matrix constructs (XA) were implanted. In each animal, cardiopulmonary bypass was used to resect the pulmonary valve and replace it with the xenogenic pulmonary valve conduits. The animals were killed after 6, 9 or 12 months. The explanted valves were examined histologically and biochemically., Results: After explantation XB showed severe cusp degeneration, which resulted in severe valvular regurgitation. In comparison, XA appeared macroscopically normal with preserved valvular function. The surface of XB were covered with an incomplete endothelial multilayer. The extracellular matrix (ECM) of XB showed pathological amounts of collagenous and elastic fibers as well as proteoglycan content combined with an increase cellularity. The XA were completely repopulated by an endothelial cell monolayer; the ECM was repopulated with a myofibroblast population comparable to native ovine heart valve tissue., Conclusions: Approaches to heart valve engineering based on acellularized/xenogenic matrices provide promising results and will hopefully led to the "ideal" valve substitute in clinical heart valve replacement.

Objectives: After a period of 5 to 10 years, biological heart valve prostheses undergo degenerative processes, which finally lead to dysfunction and complete destruction. Although many efforts have been made to identify underlying mechanisms, many questions remain unanswered. Here we evaluate immunological factors and their potential role in biological heart valve destruction., Patients and Methods: Allogeneic (n=10) and xenogeneic (n=3) aortic valvular prostheses, as well as aortic valves retrieved from transplanted human hearts, which had to be replaced because of chronic graft rejection (n=4) were analyzed. Aortic valves from human donor hearts (native) (n=4), which were considered not transplantable served as controls. Endothelial expression patterns of the following adhesion molecules were analyzed by immunohistochemistry: selectin family: ELAM-1, CD62, integrin family: VLA-1, -2, -3, -4, -5, and -6, immunoglobulin supergene family: PECAM-1, ICAM-1, and -2, and class I heavy chain proteins, complementary adhesion molecules: CD34, CD44 and the von Willebrand factor., Results: ELAM-1, ICAM-1 and -2, CD34, CD44 and class I heavy chain proteins, all molecules which play significant roles during inflammatory processes, showed stronger expression patterns in allogeneic and xenogeneic aortic heart valve prostheses compared to native or chronically rejected valves. Furthermore, the von Willebrand factor stained positive only on allogeneic and xenogeneic valves. Only mild differences were observed regarding the expression of integrin molecules and CD62., Conclusions: Immunological reactions play a major role in the degeneration of biological heart valve prostheses. This is underlined by observations made on aortic valves from chronically rejected cardiac grafts, which did not show any degenerative alterations. Thus, since immunosuppressive therapy after heart valve replacement is no reasonable alternative, novel and future approaches in "tissue engineering" will hopefully help avoid tissue degeneration, while preserving the advantage of biological tissue origin.

Endoaneurysmorrhaphy (EAR) in postinfarct ventricular aneurysms leads to excellent short-term results. However, the temporal response of EAR is widely unknown. Thus, the indication for surgical treatment of patients with ventricular aneurysms is not well defined. EAR was performed in 157 patients (6/1993-6/1999) with symptomatic ventricular aneurysms (median NYHA III). Factors influencing cardiac mortality and morbidity during follow-up were determined by univariate and multivariate analysis. Perioperative mortality was low: 5%. Mortality during follow-up was 3.3% per year, resulting in a 5-year survival rate of 78%. NYHA classification ameliorated significantly from the preoperative status compared to the follow-up period (median NYHA II; p < 0.001). Multivariate analysis identified preexisting arterial occlusive disease and advanced age (> 70 years) as significant factors influencing medium-term mortality. Implantation of the left internal mammary artery was associated with a better survival rate. Endoaneurysmorrhaphy can be performed with low perioperative mortality, will result in a significant amelioration of the cardiac clinical status and offers low medium-term mortality. Our data indicate that EAR seems to be the procedure of choice for patients with symptomatic ventricular aneurysms.

The long-term performance of two different types of flexible aortic prostheses was evaluated in 10 patients who received a stentless porcine prosthetic valve (group A) and in 18 patients who underwent aortic valve replacement with an aortic homograft (group B). In group A early postoperative angiography (5-16 days post surgery) revealed a mean gradient across the aortic prosthesis of 8 +/- 6 mmHg. Late postoperative Doppler echocardiography (3.2 +/- 0.9 years post surgery) suggested a mean gradient of 6 +/- 3 mmHg with a Doppler derived valve orifice area of 1.8 +/- 0.6 cm2. Color Doppler visualized mild prosthesis regurgitation in two of the 10 patients and two-dimensional imaging showed no significant leaflet calcification. In group B late postoperative Doppler echography (5.2 +/- 1.6 years post surgery) suggested a mean gradient of 11 +/- 14 mmHg with a mean graft orifice area of 1.8 +/- 0.5 cm2. Color Doppler revealed prosthesis regurgitation in 15 patients (severe 1, moderate 2, mild 12) and two-dimensional imaging visualized significant prosthesis leaflet calcification in two patients. The good hemodynamic function of a stentless porcine bioprosthesis which seems to be preserved for at least several years indicates that the use of the flexible aortic xenograft is worthwhile pursuing. The long-term performance of an aortic homograft is relatively poor and may be due to unsolved problems with regard to sterilizing and storing the valves.