Joerg S. Sachweh

Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation

There is a clear clinical requirement for the design and development of living, functional, small-calibre arterial grafts. Here, we investigate the potential use of a small diameter, tissue-engineered artery in a pre-clinical study in the carotid artery position of sheep. Small-calibre ( approximately 5 mm) vascular composite grafts were molded using a fibrin scaffold supported by a poly(L/D)lactide 96/4 (P(L/D)LA 96/4) mesh, and seeded with autologous arterial-derived cells prior to 28 days of dynamic conditioning. Conditioned grafts were subsequently implanted for up to 6 months as interposed carotid artery grafts in the same animals from which the cells were harvested. Explanted grafts (n = 6) were patent in each of the study groups (1 month, 3 months, 6 months), with a significant stenosis in one explant (3 months). There was a complete absence of thrombus formation on the luminal surface of grafts, with no evidence for aneurysm formation or calcification after 6 months in vivo. Histological analyses revealed remodeling of the fibrin scaffold with mature autologous proteins, and excellent cell distribution within the graft wall. Positive vWf and eNOS staining, in addition to scanning electron microscopy, revealed a confluent monolayer of endothelial cells lining the luminal surface of the grafts. The present study demonstrates the successful production and mid-term application of an autologous, fibrin-based small-calibre vascular graft in the arterial circulation, and highlights the potential for the creation of autologous implantable arterial grafts in a number of settings.

Novel "biomechanical" polymeric valve prostheses with special design for aortic and mitral position: a future option for pediatric patients?

In children, systemic heart valve replacement with bioprostheses is associated with accelerated valve degeneration, and mechanical prostheses require permanent anticoagulation. Novel “biomechanical” polymeric valve prostheses (“bio” = flexible, “mechanical” = synthetic), solely made of polycarbonate urethane (PCU), were tested in vitro and in a growing animal (calf) model with the aim of improved durability without permanent anticoagulation. The trileaflet aortic prosthesis has diminished pressure loss and reduced stress and strain peaks. The asymmetric bileaflet mitral valve mimics natural nonaxial inflow. The valves underwent long-term in vitro testing and in vivo testing in growing calves for 20 weeks [mitral (7), aortic (7)] with comparison to different commercial bioprostheses [mitral (7), aortic (2)]. In vitro durability of PCU valves was proved up to 20 years. Survival of PCU valves versus bioprostheses was 7 versus 2 mitral and 5 versus 0 aortic valves, respectively. Two animals with PCU aortic valves died of pannus overgrowth causing left ventricular outflow tract obstruction. 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 to bioprostheses. The novel polymeric valve prostheses revealed superior durability compared to current bioprostheses in growing animal model without permanent anticoagulation and thus, may be a future option for pediatric patients.

Mechanical circulatory support in pediatric patients with the MEDOS assist device.

Mechanical circulatory support is successfully applied to patients with low cardiac output. The MEDOS-System provides pulsatile ventricular assistance for patients of all age groups, including neonates. We report our experience with seven consecutive pediatric patients with the MEDOS-VAD. The indication was bridge to transplantation in all patients. Mean age was 7.3 ± 6.5 years (range 0.75–16.9 years) and mean weight was 26.3 ± 21.7 kg (range 5.9–60 kg). Perioperative survival was 100%; complications occurred in six patients (86%; two cerebral embolism/bleeding, two rethoracotomy, two exchange of pump chamber due to thrombus formation after 4 and 9 days). Mean duration of support was 20.4 ± 10.8 days (range 6–38 days). Bilirubin decreased from 3.5 ± 2.6 mg/d to 2.1 ± 1.2 mg/d. Hospital mortality was three of seven patients who did not receive an organ offer in time. All patients who underwent subsequent heart transplantation (four of seven patients; 57%) were discharged from the hospital. Mechanical circulatory support with the MEDOS-System can be performed successfully in pediatric patients of any age. Secondary organ functions improve under this pulsatile circulatory assistance. Hemorrhage and thromboembolic events are the most frequent complications.

Prevention of Postoperative Pericardial Adhesions With TachoSil

BACKGROUND The prevention of the pericardial adhesions largely accountable for the technical difficulty and risk of injury inherent to resternotomy continues to gain in importance with the increasing frequency of reoperations. The hemostatic sponge TachoSil (Nycomed Austria GmbH, Linz, Austria), has shown promising results in adhesion prevention in several regions of the body. This study was designed to evaluate its effectiveness in the prevention of pericardial adhesions in comparison with the Gore-Tex (W. L. Gore and Assoc, Flagstaff, AZ) surgical membrane and a control. METHODS Twenty-four rabbits were distributed into 3 groups: TachoSil, Gore-Tex, or no barrier agent (control). After median sternotomy and pericardiotomy, the cardial surface was exposed to the aggravating effects of room air, irrigation, and gauze abrasion for one hour. A pericardial defect was created and repaired with one of the barrier agents, or left uncovered (control). Resternotomy was performed after 6 months for the evaluation of adhesion formation. RESULTS Significantly fewer macroscopic adhesions were observed with TachoSil than Gore-Tex in all regions (p < 0.05) excluding the coronary arteries, where the difference in favor of TachoSil did not achieve significance (0.05< p-value <0.10). TachoSil also demonstrated significantly fewer retrosternal adhesions than the control, as well as a universal non-significant trend of fewer adhesions in all regions. The limited lesions present in the TachoSil group were filmy in nature and removed with blunt dissection relatively easily. No significant differences were found between Gore-Tex and the control. Microscopically, the least pronounced fibrosis formation and inflammatory reaction was detected with TachoSil. CONCLUSIONS TachoSil is effective in the prevention of pericardial adhesions.

The Aachen miniaturized heart-lung machine--first results in a small animal model.

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth-weight newborns. Taking these considerations into account, the Aachen miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross-clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O(2) and CO(2)) may reduce circuit-induced complications during heart surgery in neonates.

Systemic mechanical heart valve replacement in children under 16 years of age

SummaryWe report the early and late outcome following left-sided mechanical heart valve replacement in children. Between 10/1981 and 02/2001, 27 children (13 male, mean age 7.2 ± 5.2 years, range 0.53–15.7 years) underwent mechanical mitral (MVR 16), aortic (AVR 9) or double valve replacement (DVR 2) with St. Jude Medical valves. Eighteen children (66.7%) had undergone previous cardiac surgery. Valve disease was congenital in 23, due to endocarditis in 2 and rheumatic in 2 patients. Concomitant cardiac surgery was performed in 12 patients (44.4%). Operative mortality was 3.7% (1/27). Perioperative complications were complete heart block (5) and myocardial infarction (1). Mean follow-up was 6.5±5.9 years (range 0.4–19 years, total 169.9 patient-years). There was one valve-related late death due to mitral valve thrombosis without phenprocoumon. Actuarial survival after 1, 5 and 10 years was 93, 93 and 93%. Late complications included endocarditis (2), minor hemorrhagic event (1) and stroke (1). Overall 10-year freedom from any anticoagulation-related adverse event under phenprocoumon was 91% (1.3%/patient year). Eight patients required reoperations: re-MVR (5; outgrowth of the prostheses (3), pannus overgrowth (2)), closure of paravalvular leak after AVR (2), and re- DVR (1; endocarditis). Actuarial freedom from reoperation after 1, 5 and 10 years was 96, 88 and 76%.ConclusionMechanical valve prostheses are a valuable option for left-sided heart valve replacement in pediatric patients with good results. Operative mortality and the incidence of any valve-related events as endocarditis, reoperation, thromboembolism or anticoagulation related bleeding is acceptable.

A Newly Developed Miniaturized Heart-Lung Machine—Expression of Inflammation in a Small Animal Model

Cardiopulmonary bypass may cause severe inflammatory reactions and multiorgan failure, especially in premature and low-weight infants. This is due in part to the large area of contact with extrinsic surfaces and the essential addition of foreign blood. Thus, we developed a new miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102mL (including arterial and venous lines) and tested it in a small animal model. Seven Chinchilla Bastard rabbits were perfused with the MiniHLM (dynamic priming volume 127mL). Seven animals serving as a control were perfused using Dideco Kids and a Stöckert roller pump (modified dynamic priming volume 149mL). The rabbits were anesthetized and sternotomized, followed by cannulation of the aorta and the right atrium. The aorta was clamped for 1h. Blood for examination of inflammation (TNF-α, IL-1β, IL-6, IL-8, and IL-10) and blood gas analysis were taken before skin incision, 5min before opening of the aorta, 15min after opening of the aorta, and 4 h after the initiation of cardiopulmonary bypass. The parameters of inflammation were expressed by means of the comparative C(T) method (ΔΔC(T) method). After gradual reduction of perfusion with the HLM, the heart was decannulated, and the sternum was closed. All rabbits were successfully weaned from cardiopulmonary bypass. Blood gas analysis was unremarkable in all cases. Foreign blood was not administered. Although statistical significance was not achieved, there was a reduced expression of inflammatory markers in the MiniHLM group. The newly developed MiniHLM prototype was tested successfully in a small animal model in terms of technical function and expression of inflammation. Upcoming tests with the industrially manufactured MiniHLM may reveal the advantages of the MiniHLM in comparison with the conventional HLM.

Ross Procedure in Neonates and Infants: A European Multicenter Experience.

BACKGROUND Infants and neonates with severe left ventricular outflow tract obstruction may require pulmonary autograft replacement of the aortic root. In this retrospective multicenter cohort study, we present our experience with the Ross procedure in neonates and infants with a focus on midterm survival and pulmonary autograft durability. METHODS A retrospective observational study was performed in 76 infants (aged less than 1 year) operated on in six congenital cardiac centers in The Netherlands and Germany between 1990 and 2013. RESULTS Patients had a pulmonary autograft replacement of the aortic valve with (68%) or without (32%) septal myectomy. Median patient age was 85 days (range, 6 to 347). Early mortality (n = 13, 17%) was associated with neonatal age, preoperative use of intravenous inotropic drugs, and congenital aortic arch defects. Five patients (9%) died during follow-up. Freedom from autograft reintervention was 98% at 10 years. Echocardiography demonstrated good valve function, with no or trace regurgitation in 73% of patients. Freedom from right ventricular outflow tract reintervention was 51% at 10 years. Univariable analysis demonstrated superior freedom from reintervention of pulmonary homografts compared with aortic homografts or xenografts. CONCLUSIONS Pulmonary autograft replacement of the aortic valve in neonates and infants is a high-risk operation but offers a durable neoaortic valve. Midterm durability reflects successful adaptation of the autograft to the systemic circulation. Late mortality associated with heart failure was an unexpected finding.

Pancarditis in a five-year-old boy affecting tricuspid valve and ventricular septum.

A five-year-old boy with a structurally normal heart and recent history of adenotomy and gastroenteritis presented with Staphylococcus aureus pancarditis including endocarditis of the tricuspid valve and abscess of the ventricular septum. Surgical treatment consisted of debridement of the valvar vegetations and of the septal abscess. A seven-day continuous mediastinal irrigation with iodine solution was conducted to eliminate local infection sites as well as to prevent from constrictive pericarditis. The patient recovered uneventfully and is in excellent clinical condition with no residues one year after surgery.

ENDOXY - Development of a Biomimetic Oxygenator-Test-Device.

Objective This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term therapy. Tissue engineering uses autologous cell sources to overcome the immunogenic barriers of biomaterials. Surface coating with endothelial cells might improve hemocompatibility and thus prevent immunogenic reactions of the body. In this study this concept is applied to endothelialise a gas-permeable membrane to develop a biomimetic oxygenator test-device (ENDOXY). Methods ENDOXY—a multifunctional test-system was developed to endothelialise a gas-permeable membrane suitable for cell culture and to test the cell retention under shear stress and to measure gas transfer through it. Results Successful endothelialisation of the membrane was achieved and cells showed characteristic endothelial morphologies. They stained positive for endothelial markers. The number of cells aligned with shear stress and cell retention after blood perfusing experiments was high. Gas transfer is observed via uncoated and endothelialised membranes. Conclusion The study showed promising results with regard to system design, endothelialisation, and cell retention under shear stress conditions. It strongly encourages further research into the system by testing different membrane materials to design a biomimetic membrane surface and pave way for a fully hemocompatible oxygenator.