Formation of a stenotic fibrotic membrane at the distal anastomosis of bovine jugular vein grafts (Contegra) after right ventricular outflow tract reconstruction.
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Biomedical subjects
Publications and source records attributed to Alexander Kadner.
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OBJECTIVE: The objective of this study was to assess the safety of directly closing the septum primum during the correction of atrioventricular canal defects. METHODS: We performed a retrospective analysis of our experience with direct closure of the septum primum during the repair of atrioventricular canal defect. The series consisted of 28 consecutive patients presenting with a partial (15 patients) and complete (13 patients) atrioventricular canal defect. The cleft in the atrioventricular valve was closed completely in 25 patients and partially in 3 patients (those with a small left lateral leaflet). In complete atrioventricular canal, the ventricular septum defect was closed with a patch of polytetrafluoroethylene (Gore-Tex, W. L. Gore & Associates, Inc, Flagstaff, Ariz) or xenopericardium. Follow-up was complete and ranged from 3 to 21 months (median 11 months). RESULTS: There were no early or late deaths and no surgical complications. The septum primum defect was closed completely in all patients as assessed by echocardiography. All the patients were in sinus rhythmus, and none had even a temporary complete atrioventricular block. The surgical result and heart rhythm have remained stable over time. CONCLUSIONS: Direct closure of the septum primum is an easy, quick, and safe procedure during repair of atrioventricular defects.
BACKGROUND: Reducing the negative side effects associated with extracorporeal circulation is the major advantage of off-pump revascularization. However, side clamping of a calcified aorta for proximal anastomoses can cause emboli, resulting in neurologic damage. This problem has been addressed by introducing a mechanical anastomosis device (Symmetry, St Jude Medical) that allows vein-to-aorta anastomosis without manipulating the aorta. This report describes our experience with this device. METHODS: Between June 2001 and April 2002, 77 connectors (1.3 per patient) were deployed in 61 patients (51 men and 10 women; mean age, 68 +/- 8.6 years) undergoing off-pump coronary artery bypass grafting or beating-heart revascularization. Intraoperative quality assessment included transit-time flow measurement (Medistim) and indocyanine green-based angiography (Spy, Novadaq). RESULTS: The surgeons were meticulously trained in loading of the device. No postoperative neurologic deficits were detected. Fifty-three patients had an uneventful course. However, 8 (13.1%) patients with 12 implanted connectors were symptomatic within 8 months (1 day to 8 months). Angiography revealed significant (95%) stenosis or even occlusion of the proximal vein-to-aorta anastomosis at the level of all connectors. Four patients underwent reoperation (2 dilated-stented and 2 treated with drugs). CONCLUSION: On the basis of these observations, the routine use of the connector was halted at our institution. At the moment, the use of this therapy is reserved for patients with severely calcified aortas with no technical alternative. Further investigations appear necessary to evaluate the clinical patterns of this otherwise promising technology.
Harmonious reduction of the posterior annulus of the mitral valve can be a useful adjunct to obtain complete valve competence in case of annular dilatation. We present a technique with the use of two resorbable sutures that overlap over the middle third of the posterior annulus that was used in 10 children with good short-term results. Resorption of the sutures should permit subsequent normal growth of the mitral valve. If the primary cause of valvular regurgitation was corrected, it can be expected that the repair will remain stable after resorption of the sutures.
OBJECTIVES: Off-pump coronary artery bypass grafting may decrease operative morbidity when compared to on-pump bypass grafting; however, it is technically demanding and thus quality control is essential. This study assesses the clinical feasibility of a new, indocyanine green (ICG)-based imaging system (SPY; Novadaq Technologies; Toronto, ON, Canada) to monitor the quality of anastomoses and grafts in off-pump revascularization. SETTING: Thirty-eight consecutive patients undergoing nonemergent coronary artery bypass grafting without the use of extracorporeal circulation at two Swiss cardiac surgery clinics were included. On completion of bypass grafts, the quality of the grafts was assessed using the ICG-based imaging system. The imaging device comprises an 806-nm laser light source that is used to cause ICG to fluoresce and a near infrared-sensitive charged couple device videocamera that is used to capture the fluorescence images. ICG was administered through the central venous line, and images were acquired during the first pass of the ICG through the field of view. Graft flow (qualitative) and the quality of the grafts and anastomoses were assessed intraoperatively. RESULTS: Between March 2002 and September 2002, a total of 38 patients (26 men and 12 women; mean +/- SD age, 64.6 +/- 10.5 years; body mass index, 27.1 +/- 2.9) underwent surgery and imaging at two institutions. One hundred seven of 124 grafts (45 arteries and 62 veins) were analyzed. Seventeen grafts could not be assessed due to difficulties in positioning. The imaging system was easy to handle, and no adverse reactions to ICG were observed. Four of the 107 grafts imaged required revision (three anastomotic constrictions and one graft dissection). Each imaging sequence required approximately 1.25 to 2.5 mg of ICG. The images were equivalent to angiography without the need for radiographs and catheter insertion. In addition, the course of coronaries that would otherwise be difficult to locate in obese patients could be detected using the imaging system. Biochemical and ECG data demonstrated an absence of intraoperative or postoperative myocardial damage, and no liver enzyme elevation or renal dysfunction. CONCLUSIONS: This study supports the clinical utility of a ICG-based imaging system for the assessment of the quality of bypass grafts, which appears to be safe and simple to use.
BACKGROUND: Surgical closure of isolated ventricular septal defect (VSD) through partial inferior sternotomy offers the advantages of a much shorter, cosmetically superior skin incision, potentially improved sternal stability, a lower rate of infection, and less postoperative pain. We report our technique and results of use of inferior partial sternotomy for closure of isolated VSD in children. PATIENTS AND METHODS: From July 2002 to July 2003, 24 consecutive patients with a median age of 4.5 months (range, 1 month-4.5 years) underwent partial inferior sternotomy for isolated VSD closure. The length of the incision ranged from 4 to 6 cm. Special features of the approach included T incision of the lower sternum (from the fourth intercostal space to the xiphoid), establishment of cardiopulmonary bypass with central cannulation, aortic cross-clamping, and cardioplegic arrest. All VSDs were approached through right atriotomy. Perimembranous VSDs were exposed after detachment of the anterior leaflet of the tricuspid valve and were closed with a continuous suture. Muscular VSDs were approached directly. Perioperative and postoperative echocardiographic findings were available for all patients. Follow-up was complete. RESULTS: There was no mortality or significant surgical morbidity. Median cross-clamping and cardiopulmonary bypass times were 43 and 103 minutes, respectively. All patients were in sinus rhythm. Perioperative and postoperative echocardiography confirmed the absence of any residual defects in perimembranous VSDs and the presence of a trace residual VSD in 4 patients with muscular VSDs. Optimal healing of the partial sternotomy was obtained in all patients. CONCLUSIONS: Inferior partial sternotomy is less invasive than and cosmetically superior to full sternotomy. It provides excellent results when applied to isolated VSD with standard surgical techniques.
Recently the Symmetry Bypass System (SJM, St. Paul, MN) became available. Now the system is frequently applied for vein-graft to aorta anastomoses in off-pump coronary artery bypass operations. This report describes a complication associated with the use of the Symmetry Bypass System (SJM) in a patient undergoing a standard off-pump coronary artery bypass procedure. A novel imaging system (SPY, Novadaq, Toronto, Canada) was applied for intraoperative assessment of graft function, and this system immediately diagnosed the occlusion of the proximal mechanical anastomosis caused by a mobile atheromatous aortic plaque.
BACKGROUND: Detachment of the septal leaflet of the tricuspid valve has been described for better access to perimembranous ventricular septal defects. Detachment confined to the anterior leaflet is less known, although it provides a better exposure of the subaortic area and puts less jeopardy on the conduction tissues. METHODS: Data regarding 49 consecutive patients who had congenital perimembranous ventricular septal defect closure were retrospectively reviewed. Thirty-three patients (67%) underwent temporary detachment of the anterior leaflet of the tricuspid valve. The defect was closed with a Gore-Tex patch and a continuous suture. In 10 patients (29%), concomitant right ventricular outflow tract enlargement was performed. Follow-up was obtained in every patient (median time, 11 months; range, 2 to 26 months). RESULTS: No early or late death occurred. Closure of the ventricular septal defect was complete, with no more than trivial residual jet leaks found in perioperative echocardiography. All patients were in sinus rhythm. The tricuspid valve never showed more than mild insufficiency after repair. No patient showed subaortic obstruction. CONCLUSIONS: Detachment of the anterior leaflet of the tricuspid valve to expose the ventricular septal defect is a safe approach that allows rapid closure of the defect with a continuous suture and provides excellent results.
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OBJECTIVE: To study the early function of the bovine jugular vein (BJV) when used for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure. METHODS: Seventeen consecutive patients (median age, 12 years; range, 30 days to 40 years) who had undergone a Ross procedure with RVOT reconstruction using a BJV were reviewed. Nine patients had prior balloon valvotomy (n = 6) and/or surgical aortic valvotomy (n = 4). Additional procedures included a reduction-plasty of the ascending aorta (5 patients), a Konno procedure (2 patients), a mitral valve repair/replacement (2 patients), and others (3 patients). The size of the BJV ranged from 12 to 22 mm (median, 20 mm). RESULTS: There were no early or late deaths. None of the patients encountered any significant postoperative complications. The neo-aortic valve showed good function in all patients with no more than trivial insufficiency. At a median follow-up period of 11 months, the frequency of freedom from BJV graft dysfunction/reintervention/reoperation was 100%. One patient had moderate insufficiency of the BJV in a perioperative examination that regressed to mild insufficiency during follow-up. Overall, none of the patients had more than mild insufficiency at follow-up. Four patients showed a flow acceleration of more than 250 cm/s (equivalent to a gradient of 25 mm Hg) across the BJV, and the remaining patients had lower gradients. CONCLUSIONS: The BJV, when used to replace the pulmonary valve in the Ross procedure, showed excellent function in the early phase. The large size range and easy availability of this valved conduit are particularly attractive. Further followup is needed to determine the long-term results of its use.
BACKGROUND: We previously demonstrated the successful tissue engineering and implantation of functioning autologous heart valves based on vascular-derived cells. Human marrow stromal cells (MSC) exhibit the potential to differentiate into multiple cell-lineages and can be easily obtained clinically. The feasibility of creating tissue engineered heart valves (TEHV) from MSC as an alternative cell source, and the impact of a biomimetic in vitro environment on tissue differentiation was investigated. METHODS AND RESULTS: Human MSC were isolated, expanded in culture, and characterized by flow-cytometry and immunohistochemistry. Trileaflet heart valves fabricated from rapidly bioabsorbable polymers were seeded with MSC and grown in vitro in a pulsatile-flow-bioreactor. Morphological characterization included histology and electron microscopy (EM). Extracellular matrix (ECM)-formation was analyzed by immunohistochemistry, ECM protein content (collagen, glycosaminoglycan) and cell proliferation (DNA) were biochemically quantified. Biomechanical evaluation was performed using Instron(TM). In all valves synchronous opening and closing was observed in the bioreactor. Flow-cytometry of MSC pre-seeding was positive for ASMA, vimentin, negative for CD 31, LDL, CD 14. Histology of the TEHV-leaflets demonstrated viable tissue and ECM formation. EM demonstrated cell elements typical of viable, secretionally active myofibroblasts (actin/myosin filaments, collagen fibrils, elastin) and confluent, homogenous tissue surfaces. Collagen types I, III, ASMA, and vimentin were detected in the TEHV-leaflets. Mechanical properties of the TEHV-leaflets were comparable to native tissue. CONCLUSION: Generation of functional TEHV from human MSC was feasible utilizing a biomimetic in vitro environment. The neo-tissue showed morphological features and mechanical properties of human native-heart-valve tissue. The human MSC demonstrated characteristics of myofibroblast differentiation.
Auditory ERPs were recorded from eight tinnitus patients and 12 controls. Tone pips of 1000 and 2000 Hz, as well as the patient's tinnitus pitch (around 4000 Hz) were used. Controls received tone pips at 1000, 2000, and 4000 Hz. Tones were presented at 30, 36, 42, 48 and 54 dB/SL. The intensity dependence of the auditory N100 was calculated for each frequency in each group. Patients showed a steeper response to the tinnitus frequency than responses to the 4000 Hz tone in controls. In contrast, intensity-dependence to the 2000 Hz tones was significantly decreased in patients (two-tailed Wilcoxon-Mann-Whitney U-test, p < 0.05). Responses to the 1000 Hz tones were similar for both groups. This reduced intensity dependence is hypothesized to result from lateral inhibition arising from tinnitus related activity in the 4000 Hz isofrequency region.
BACKGROUND: Tissue engineering represents a promising approach to in vitro creation of living, autologous replacements with the potential to grow, repair, and remodel. Particularly in a congenital operation, there is a substantial need for such implantation materials. We previously demonstrated fabrication of completely autologous, functional heart valves on the basis of peripheral vascular cells. Presently the feasibility of creating pulmonary artery conduits from human umbilical cord cells was investigated. METHODS: Human umbilical cord cells were harvested and expanded in culture. Pulmonary conduits fabricated from rapidly bioabsorbable polymers were seeded with human umbilical cord cells and grown in vitro in a pulse duplicator bioreactor. Morphologic characterization of the generated neo-tissues included histology, transmission, and scanning electron microscopy. Characterization of extracellular matrix was comprised of immunohistochemistry. Extracellular matrix protein content and cell proliferation were quantified by biochemical assays. Biomechanical testing was performed using stress-strain and burst-stress tests. RESULTS: Histology of the conduits revealed viable, layered tissue and extracellular matrix formation with glycosaminoglycans and collagens I and III. Cells stained positive for vimentin and alpha-smooth muscle actin. Scanning electron microscopy showed confluent, homogenous tissue surfaces. Transmission electron microscopy demonstrated elements typical of viable myofibroblasts, such as collagen, fibrils, and elastin. Extracellular matrix proteins were significantly lower compared with native tissue; the cell content was increased. The mechanical strength of the pulsed constructs was comparable with native tissue; the static controls were significantly weaker. CONCLUSIONS: In vitro fabrication of tissue-engineered human pulmonary conduits was feasible utilizing human umbilical cord cells and a biomimetic culture environment. Morphologic and mechanical features approximated human pulmonary artery. Human umbilical cord cells demonstrated excellent growth properties representing a new, readily available cell source for tissue engineering without necessitating the sacrifice of intact vascular donor structures.
BACKGROUND: Tissue engineering of viable, autologous cardiovascular constructs with the potential to grow, repair, and remodel represents a promising new concept for cardiac surgery, especially for pediatric patients. Currently, vascular myofibroblast cells (VC) represent an established cell source for cardiovascular tissue engineering. Cell isolation requires the invasive harvesting of venous or arterial vessel segments before scaffold seeding, a technique that may not be preferable, particularly in pediatric patients. In this study, we investigated the feasibility of using umbilical cord cells (UCC) as an alternative autologous cell source for cardiovascular tissue engineering. METHODS: Human UCC were isolated from umbilical cord segments and expanded in culture. The cells were sequentially seeded on bioabsorbable copolymer patches (n = 5) and grown in vitro in laminar flow for 14 days. The UCC were characterized by flow cytometry (FACS), histology, immunohistochemistry, and proliferation assays and were compared to saphenous vein-derived VC. Morphologic analysis of the UCC-seeded copolymer patches included histology and both transmission and scanning electron microscopy. Characterization of the extracellular matrix was performed by immunohistochemistry and quantitative extracellular matrix protein assays. The tissue-engineered UCC patches were biomechanically evaluated using uniaxial stress testing and were compared to native tissue. RESULTS: We found that isolated UCC show a fibroblast-like morphology and superior cell growth compared to VC. Phenotype analysis revealed positive signals for alpha-smooth muscle actin (ASMA), desmin, and vimentin. Histology and immunohistochemistry of seeded polymers showed layered tissue formation containing collagen I, III, and glycoaminoglycans. Transmission electron microscopy showed viable myofibroblasts and the deposition of collagen fibrils. A confluent tissue surface was observed during scanning electron microscopy. Glycoaminoglycan content did not reach values of native tissue, whereas cell content was increased. The biomechanical properties of the tissue-engineered constructs approached native tissue values. CONCLUSIONS: Tissue engineering of cardiovascular constructs using UCC is feasible in an in vitro environment. The UCC demonstrated excellent growth properties and tissue formation with mechanical properties approaching native tissue. It appears that UCC represent a promising alternative autologous cell source for cardiovascular tissue engineering, offering the additional benefits of using juvenile cells and avoiding the invasive harvesting of intact vascular structures.
OBJECTIVE: Vascular-derived cells represent an established cell source for tissue engineering of cardiovascular constructs. Previously, cell isolation was performed by harvesting of vascular structures prior to scaffold seeding. Marrow stromal cells (MSC) demonstrate the ability to differentiate into multiple mesenchymal cell lineages and would offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. We studied the feasibility of using MSC as an alternative cell source for cardiovascular tissue engineering. METHODS: Human MSC were isolated from bone marrow and expanded in culture. Subsequently MSC were seeded on bioabsorbable polymers and grown in vitro. Cultivated cells and seeded polymers were studied for cell characterization and tissue formation including extracellular matrix production. Applied methods comprised flow cytometry, histology, immunohistochemistry, transmission (TEM) and scanning electron microscopy (SEM), and biochemical assays. RESULTS: Isolated MSC demonstrated fibroblast-like morphology. Phenotype analysis revealed positive signals for alpha-smooth muscle actin and vimentin. Histology and SEM of seeded polymers showed layered tissue formation. TEM demonstrated formation of extracellular matrix with deposition of collagen fibrils. Matrix protein analysis showed production of collagen I and III. In comparison to vascular-derived cell constructs quantitative analysis demonstrated comparable amounts of extracellular matrix proteins in the tissue engineered constructs. CONCLUSIONS: Isolated MSC demonstrated myofibroblast-like characteristics. Tissue formation on bioabsorbable scaffolds was feasible with extracellular matrix production comparable to vascular-cell derived tissue engineered constructs. It appears that MSC represent a promising cell source for cardiovascular tissue engineering.
Speech coding strategies for cochlear implants commonly use amplitude modulations of constant high rate pulses to differentially stimulate separate frequency channels in the cochlea. Thereby, time domain information in the fine structure of speech sounds, especially on transients, is largely lost. In gerbils with a single electrode cochlear implant was explored, whether upward and downward interval modulation of pulse trains can carry discriminable information. This question was pursued with unit recordings in primary auditory cortex (AI) and with behavioral discrimination training in a shuttle box. Units in AI showed multiple differences in the dynamic responses to the two directions of interval modulation and notably ON-response dominated patterns with increasing intervals and OFF-response dominated patterns with decreasing intervals of stimulation. In accordance with these neuronal correlates gerbils learned to distinguish the directions of interval modulation within 3 days, but only with certain specifications.
In cardiovascular tissue engineering, synthetic or biologic scaffolds serve as templates for tissue development. Currently used scaffolds showing toxic degradation and immunogenic reactions are still far from ideal. We present a new alternative method to develop completely autologous human tissue without using any scaffold materials. Human vascular cells of arterial and venous origin were cultured to form cell sheets over a 4 week period under standard conditions. Thereafter, cell sheets of each origin were folded and cultured in a newly developed frame device for an additional 4 weeks. Controls remained under standard culture conditions. Tissue development was evaluated by morphology and biochemical assays. The formation of multilayered cell sheets and production of extracellular matrix were observed in all groups. Folded and framed neo-tissue showed a solid structure, with increased matrix formation and tissue organization when compared with the control groups. DNA content indicated significantly lower cell proliferation, and hydroxyproline assay indicated significantly higher collagen content in the framed cell sheets. We present a new approach to the engineering of cardiovascular tissue without the use of biodegradable scaffold material. Three-dimensional, completely autologous human tissue may be developed on the basis of this structure, thus avoiding scaffold induced toxic degradation or inflammatory reaction.