Jörg S. Sachweh

Fibrin gel – advantages of a new scaffold in cardiovascular tissue engineering

OBJECTIVE The field of tissue engineering deals with the creation of tissue structures based on patient cells. The scaffold plays a central role in the creation of 3-D structures in cardiovascular tissue engineering like small vessels or heart valve prosthesis. An ideal scaffold should have tissue-like mechanical properties and a complete immunologic integrity. As an alternative scaffold the use of fibrin gel was investigated. METHODS Preliminary, the degradation of the fibrin gel was controlled by the supplementation of aprotinin to the culture medium. To prevent tissue from shrinking a mechanical fixation of the gel with 3-D microstructure culture plates and a chemical fixation with poly-L-lysine in different fixation techniques were studied. The thickness of the gel layer was changed from 1 to 3 mm. The tissue development was analysed by light, transmission and scanning electron microscopy. Collagen production was detected by the measurement of hydroxyproline. Injection molding techniques were designed for the formation of complex 3-D tissue structures. RESULTS The best tissue development was observed at an aprotinin concentration of 20 microg per cc culture medium. The chemical border fixation of the gel by poly-L-lysine showed the best tissue development. Up to a thickness of 3 mm no nutrition problems were observed in the light and transmission electron microscopy. The molding of a simplified valve conduit was possible by the newly developed molding technique. CONCLUSION Fibrin gel combines a number of important properties of an ideal scaffold. It can be produced as a complete autologous scaffold. It is moldable and degradation is controllable by the use of aprotinin.

Twenty years experience with pediatric pacing: epicardial and transvenous stimulation

OBJECTIVE Permanent cardiac pacing in children and adolescents is rare and often occurs by means of epicardial pacing. Based on two decades of experience, operative and postoperative data of patients with epicardial and transvenous pacing were analyzed retrospectively. METHODS Between October 1979 and December 1998, 71 patients (mean age, 5.3+/-4.2, range, 1 day-16.2 years; mean body weight, 18+/-12; range, 8-56 kg) underwent permanent pacemaker implantation. Indications were sinus node dysfunction and atrio-ventricular block following surgery for congenital heart disease (69%), or congenital atrioventricular block (31%). Pacing was purely atrial (1.4%), purely ventricular (73%), ventricular with atrial synchronization (5. 6%), or atrioventricular synchronized (20%). Epicardial pacing was established in 49 (69%), transvenous in 22 (31%) patients. Follow-up was 3.4+/-3.8 years (epicardial) and 3.0+/-4.0 years (transvenous). RESULTS Epicardial leads were implanted in younger patients (mean age: 4.5 vs. 7.0 years, P<0.05) and preferably after surgery induced atrioventricular block (78 vs. 46%, P<0.05). The youngest patient with transvenous pacing was 1.3 years old (weight, 8.5 kg). At implantation epicardial ventricular stimulation threshold at 1.0 ms was 1.07+/-0.46 vs. 0.53+/-0.31 V (transvenous) (P<0.05). The age-adjusted rate of lead-related reoperations was significantly higher in patients with epicardial leads (P<0.05), mainly due to increasing chronic stimulation thresholds resulting in early battery depletion. In three patients who received steroid-eluting epicardial leads initial low thresholds persisted after five month to one years. In two patients with recurrent epicardial threshold increase, steroid-eluting epicardial leads led to good acute and chronic thresholds after nine to 15 month. Two post-operative death (2.8%) were probably due to a dysfunction of the (epicardial) pacing system. CONCLUSIONS Transvenous pacing in the pediatric population is associated with a lower acute stimulation threshold and a lower rate of lead-related complications. If epicardial pacing is necessary (e. g. small body weight, special intracardiac anatomy (e.g. Fontan), impossible access to superior caval vein), steroid-eluting leads may be considered.

Anatomical risk factors for mortality and cardiac morbidity after arterial switch operation

BACKGROUND The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.

Tissue-Engineered Small-Caliber Vascular Graft Based on a Novel Biodegradable Composite Fibrin-Polylactide Scaffold

Small-caliber vascular grafts (< or =5 mm) constructed from synthetic materials for coronary bypass or peripheral vascular repair below the knee have poor patency rates, while autologous vessels may not be available for harvesting. The present study aimed to create a completely autologous small-caliber vascular graft by utilizing a bioabsorbable, macroporous poly(L/D)lactide 96/4 [P(L/D)LA 96/4] mesh as a support scaffold system combined with an autologous fibrin cell carrier material. A novel molding device was used to integrate a P(L/D)LA 96/4 mesh in the wall of a fibrin-based vascular graft, which was seeded with arterial smooth muscle cells (SMCs)/fibroblasts and subsequently lined with endothelial cells. The mold was connected to a bioreactor circuit for dynamic mechanical conditioning of the graft over a 21-day period. Graft cell phenotype, proliferation, extracellular matrix (ECM) content, and mechanical strength were analyzed. alpha-SMA-positive SMCs and fibroblasts deposited ECM proteins into the graft wall, with a significant increase in both cell number and collagen content over 21 days. A luminal endothelial cell lining was evidenced by vWf staining, while the grafts exhibited supraphysiological burst pressure (>460 mmHg) after dynamic cultivation. The results of our study demonstrated the successful production of an autologous, biodegradable small-caliber vascular graft in vitro, with remodeling capabilities and supraphysiological mechanical properties after 21 days in culture. The approach may be suitable for a variety of clinical applications, including coronary artery and peripheral artery bypass procedures.

Closure of atrial septal defects via limited right anterolateral thoracotomy as a minimal invasive approach in female patients

OBJECTIVE The closure of atrial septal defects via sternotomy is a low-risk and high-benefit procedure. Limited right anterolateral thoracotomy is an alternative approach with regard to cosmetic aspects. However, it is discussed that a lateral approach is not appropriate for more complex lesions and is associated with an increased incidence of phrenic nerve damage. METHODS AND RESULTS The perioperative and long-term outcomes (mean follow-up time: 73.2 months) of 87 female patients, mean age 20.4 years (range: 3-56 years), operated on for all types of atrial septal defects via limited right anterolateral thoracotomy between 1982 and 1993, were analysed retrospectively. Special features of the operation technique were a limited skin incision, protection of mammary gland tissue, prevention of phrenic nerve damage, and aortic cannulation in all patients. There were no intraoperative complications. Postoperative complications occurred in 12/87 patients including one rethoracotomy for postoperative bleeding and one late pericardial tamponade due to coumadine overdose. Follow-up was assessed by a survey obtained by the patients or their parents, and their family doctors in 79 patients (90.8%) Cardiac symptoms, mostly supraventricular arrhythmias, were observed in 13.9%. Echocardiography revealed mild tricuspid valve regurgitation (one patient) and mild mitral valve incompetence (one patient with ostium primum defect); there were no residual shunts. Cosmetic results were considered good and excellent in 87.3% and satisfactory in 8.9%. Three patients (3.8%) complained of a broad scar. Anaesthetic areas and optional scar pain were quite frequent (16.5%), whereas restriction of shoulder movement, breast asymmetry and scoliosis were rare. In summary, only one patient, suffering from intercostal neuralgia, would prefer sternotomy. CONCLUSION Limited right anterolateral thoracotomy has a high cosmetic acceptance and was proven to be safe and effective for closure of any kind of atrial septal defects. Therefore, it is recommended as standard approach for atrial septal defects especially in female patients. reserved.

Development of a composite degradable/nondegradable tissue-engineered vascular graft.

The present study aimed to determine the feasibility of constructing a reinforced autologous vascular graft by combining the advantages of fibrin gel as an autologous cell carrier material with the inherent mechanical strength of an integrated mesh structure. It was hypothesized that the mesh and dynamic culture conditions could be combined to generate mechanically stable and implantable vascular grafts within a shorter cultivation period than traditional methods. A two-step moulding technique was developed to integrate a polyvinylidene fluoride (PVDF) mesh (pore size: 1-2 mm) in the wall of a fibrin-based vascular graft (I.D. 5 mm) seeded with carotid myofibroblasts. The graft was cultured under increasing physiological flow conditions for 2 weeks. Histology, burst strength, and suture retention strength were evaluated. Cell growth and tissue development was excellent within the fibrin gel matrix surrounding the PVDF fibers, and tissue structure demonstrated remarkable similarity to native tissue. The grafts were successfully subjected to physiological flow rates and pressure gradients from the outset, and mechanical properties were enhanced by the mesh structure. Mean suture retention strength of the graft tissue was 6.3 N and the burst strength was 236 mm Hg. Using the vascular composite graft technique, the production of tissue engineered, small-caliber vascular grafts with good mechanical properties within a conditioning period of 14 days is feasible.

Aortopexy in severe tracheal instability: short-term and long-term outcome in 29 infants and children

BACKGROUND Tracheal instability is a hazardous situation after operation for esophageal atresia. In cases with life-threatening apneas, aortopexy is a therapeutic option. To assess efficacy, short-term and long-term outcome was analyzed retrospectively. METHODS Between 1985 and 2000, 29 patients (age, 1.5 months to 5.2 years) were operated on. A flaccid trachea after operation for esophageal atresia was the cause for life-threatening apneas in 27, and there was external vascular compression in 2 patients. The operative procedure consisted of ventropexy of the aortic arch to the sternum and ventral thoracic wall. RESULTS There was neither early nor late mortality. A reversible lesion of the phrenic nerve was observed in 2 patients, a pneumothorax in 3, and secondary wound healing in 1. In all but 1 patient symptoms improved markedly or disappeared within days or within the first 3 months postoperatively. An increased susceptibility to respiratory infections was observed in long-term follow-up. CONCLUSIONS Aortopexy can be performed with no mortality and low morbidity. Aortopexy is effective to prevent further life-threatening apneas, but does not prevent an increased susceptibility to respiratory infections.

A multicentre evaluation of the autograft procedure for young patients undergoing aortic valve replacement: update on the German Ross Registry

OBJECTIVES Conventional aortic valve replacement (AVR) in young, active patients represents a suboptimal solution in terms of long-term survival, durability and quality of life. The aim of the present work is to present an update on the multicentre experience with the pulmonary autograft procedure in young, adult patients. METHODS Between 1990-2013, 1779 adult patients (1339 males; 44.7 ± 11.6 years) underwent the pulmonary autograft procedure in 8 centres. All patients underwent prospective clinical and echocardiographic examinations annually. The mean follow-up was 8.3 ± 5.1 years (range 0-24.3 years) with a total cumulative follow-up of 14 288 years and 662 patients having a follow-up of at least 10 years. RESULTS The early (30-day) mortality rate was 1.1% (n = 19). Late (>30 day) survival of the adult population was comparable with the age- and gender-matched general population (observed deaths: 101, expected deaths: 91; P = 0.29). Freedom from autograft reoperation at 5, 10 and 15 years was 96.8, 94.7 and 86.7%, respectively, whereas freedom from homograft reoperation was 97.6, 95.5 and 92.3%, respectively. The overall freedom from reoperation was 94.9, 91.1 and 82.7%, respectively. Longitudinal modelling of functional valve performance revealed a low (<5%) probability of a patient being in higher autograft regurgitation grades throughout the first decade. Similarly, excellent homograft function was observed throughout the first 15 years. CONCLUSION The autograft principle results in postoperative long-term survival comparable with that of the age- and gender-matched general population and reoperation rates within the 1%/patient-year boundaries and should be considered in young, active patients who want to avoid the shortcomings of conventional prostheses.

Allergy to Pacemaker Silicone Compounds: Recognition and Surgical Management

Silicone is a widely used biomaterial. Contact allergy, particularly to silicone components of pacemaker coatings, is uncommon. We present a 12-year-old girl with a history of complex congenital heart disease and acquired complete heart block excluding transvenous lead placement. Contact allergy to silicone led to multiple surgical interventions until the etiology for recurrent pacemaker wound complications was discovered. The key to diagnosis was a specific manufacturers patch test. Complete removal of the former pacing system and placement of custom-made silicone free pacemaker components and epicardial use of silicone free transvenous leads were essential for successful therapy.

New Flexible Polymeric Heart Valve Prostheses for the Mitral and Aortic Positions

OBJECTIVE Current prosthetic heart valves necessitate permanent anticoagulation or have limited durability and impaired hemodynamic performance compared with natural valves. We report in vivo and in vitro results with new polymeric valve prostheses that have a special design for the mitral and aortic positions. The aims are improved durability and elimination of the need for permanent anticoagulation. METHODS The mitral and aortic prostheses (Adiam Life Science, Erkelenz, Germany) are made entirely of polycarbonate urethane (PCU). The bileaflet asymmetric mitral valve mimics natural, nonaxial inflow, which creates a left ventricular vortex, saving energy for systolic ejection of blood. The trileaflet aortic prosthesis has diminished pressure loss and reduced stress and strain peaks at the commissures. The valves were subjected to long-term in vitro testing and in vivo testing in a growing calf model (20 weeks; 7 mitral and 7 aortic valves) with comparison with 2 commercial bioprostheses (7 mitral, 2 aortic). Two-dimensional echocardiography was performed after implantation and prior to sacrifice with autopsy and valve examination. RESULTS In vitro durability of the PCU valves was proved up to 20 years. In vivo durability and hemodynamics were superior to those of all bioprostheses. Survival of PCU valves versus bioprostheses was 7 versus 2 mitral valves and 5 versus 0 aortic valves, respectively. Two animals with PCU aortic valves died of pannus overgrowth that caused severe left ventricular outflow tract obstruction without changes in the valves. Degeneration and calcification were mild (mitral) and moderate (aortic) in PCU valves but were severe in biological valves. There was no increased thrombogenicity of the PCU valves compared with bioprostheses. CONCLUSION The new flexible polymeric aortic and mitral valve prostheses were superior to current bioprostheses in animal testing.