Tissue-engineered vascular grafts form neovessels that arise from regeneration of the adjacent blood vessel.

We developed a tissue-engineered vascular graft composed of biodegradable scaffold seeded with autologous bone marrow-derived mononuclear cells (BMMCs) that is currently in clinical trial and developed analogous mouse models to study mechanisms of neovessel formation. We previously reported that seeded human BMMCs were rapidly lost after implantation into immunodeficient mice as host macrophages invaded the graft. As a consequence, the resulting neovessel was entirely of host cell origin. Here, we investigate the source of neotissue cells in syngeneic BMMC-seeded grafts, implanted into immunocompetent mouse recipients. We again find that seeded BMMCs are lost, declining to 0.02% at 14 d, concomitant with host macrophage invasion. In addition, we demonstrate using sex-mismatched chimeric hosts that bone marrow is not a significant source of endothelial or smooth muscle cells that comprise the neovessel. Furthermore, using composite grafts formed from seeded scaffold anastomosed to sex-mismatched natural vessel segments, we demonstrate that the adjacent vessel wall is the principal source of these endothelial and smooth muscle cells, forming 93% of proximal neotissue. These findings have important implications regarding fundamental mechanisms underlying neotissue formation; in this setting, the tissue-engineered construct functions by mobilizing the body's innate healing capabilities to "regenerate" neotissue from preexisting committed tissue cells.

Determining the fate of seeded cells in venous tissue-engineered vascular grafts using serial MRI.

A major limitation of tissue engineering research is the lack of noninvasive monitoring techniques for observations of dynamic changes in single tissue-engineered constructs. We use cellular magnetic resonance imaging (MRI) to track the fate of cells seeded onto functional tissue-engineered vascular grafts (TEVGs) through serial imaging. After in vitro optimization, murine macrophages were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and seeded onto scaffolds that were surgically implanted as inferior vena cava interposition grafts in SCID/bg mice. Serial MRI showed the transverse relaxation times (T(2)) were significantly lower immediately following implantation of USPIO-labeled scaffolds (T(2) = 44 ± 6.8 vs. 71 ± 10.2 ms) but increased rapidly at 2 h to values identical to control implants seeded with unlabeled macrophages (T(2) = 63 ± 12 vs. 63 ± 14 ms). This strongly indicates the rapid loss of seeded cells from the scaffolds, a finding verified using Prussian blue staining for iron containing macrophages on explanted TEVGs. Our results support a novel paradigm where seeded cells are rapidly lost from implanted scaffolds instead of developing into cells of the neovessel, as traditionally thought. Our findings confirm and validate this paradigm shift while demonstrating the first successful application of noninvasive MRI for serial study of cellular-level processes in tissue engineering.

Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients.

In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.

Local tenomodulin absence, angiogenesis, and matrix metalloproteinase activation are associated with the rupture of the chordae tendineae cordis.

BACKGROUND: Rupture of the chordae tendineae cordis (CTC) is a well-known cause of mitral regurgitation. Despite its importance, the mechanisms by which the CTC is protected and the cause of its rupture remain unknown. CTC is an avascular tissue. We investigated the molecular mechanisms underlying the avascularity of CTC and the correlation between avascularity and CTC rupture. METHODS AND RESULTS: We found that tenomodulin, which is a recently isolated antiangiogenic factor, was expressed abundantly in the elastin-rich subendothelial outer layer of normal rodent, porcine, canine, and human CTC. Conditioned medium from cultured CTC interstitial cells strongly inhibited tube formation and mobilization of endothelial cells; these effects were partially inhibited by small-interfering RNA against tenomodulin. The immunohistochemical analysis was performed on 12 normal and 16 ruptured CTC obtained from the autopsy or surgical specimen. Interestingly, tenomodulin was locally absent in the ruptured areas of CTC, where abnormal vessel formation, strong expression of vascular endothelial growth factor-A and matrix metalloproteinases, and infiltration of inflammatory cells were observed, but not in the normal or nonruptured area. In anesthetized open-chest dogs, the tenomodulin layer of tricuspid CTC was surgically filed, and immunohistological analysis was performed after several months. This intervention gradually caused angiogenesis and expression of vascular endothelial growth factor-A and matrix metalloproteinases in the core collagen layer in a time-dependent manner. CONCLUSIONS: These findings provide evidence that tenomodulin is expressed universally in normal CTC in a concentric pattern and that local absence of tenomodulin, angiogenesis, and matrix metalloproteinase activation are associated with CTC rupture.

Therapeutic angiogenesis using tissue engineered human smooth muscle cell sheets.

OBJECTIVE: Peripheral arterial disease (PAD) can have severe consequences on patient mortality and morbidity. In contrast to approaches using growth factor administration or isolated cell transplantation, we attempted to develop an alternative method for ischemic therapy using the transplantation of tissue engineered cell sheets with angiogenic potential. METHODS AND RESULTS: Human smooth muscle cell (SMC) and fibroblast cell (FbC) sheets were harvested from temperature-responsive culture dishes and transplanted into ischemic hind limbs of athymic rats. ELISA showed significantly increased in vitro secretion of angiogenic factors by SMCs in comparison to FbCs. Twenty-one days after transplantation, laser doppler analysis demonstrated significantly increased blood perfusion in the SMC group. Perfusion with Indian ink and immunohistochemistry also revealed significantly greater numbers of functional capillaries in the SMC group. Finally, cell tracing experiments revealed that some SMCs from the transplanted cell sheets migrated into the ischemic tissues, contributing to newly formed vessels. CONCLUSIONS: SMC sheet transplantation allows for controlled and localized delivery of cells that possess angiogenic potential directly to ischemic tissues. Through the secretion of angiogenic factors, as well as cell migration and integration with newly formed vessels, SMC sheet transplantation provides an effective method for the revascularization of ischemic tissues.

Two Cases of Aortic Root Replacement After Fontan Completion.

Aortic root dilatation is a well-known complication in patients with congenital aortic valve malformation, tetralogy of Fallot, or a double outlet right ventricle. We report two rare patients who underwent composite graft replacement of the aortic root with a mechanical valve, the so-called Bentall-type operation, after Fontan completion. The pathological examination on the resected aortic wall revealed mucoid degeneration in tunica media and elastic fiber fragmentation. Our report emphasizes the need for close observation of these patients over a long-term period.

Subaortic stenosis associated with systolic anterior motion.

Left ventricular outflow tract obstruction in children is classified according to the site of the obstruction into a supra-aortic type, valvular type, and subaortic type (subaortic stenosis). Subaortic stenosis, in turn, is classified into two major subtypes, i.e., a discrete type, which accounts for most cases and a tunnel type, and one minor subtype, the accessory mitral tissue type, which is rare. Systolic anterior motion (SAM) is a phenomenon that is commonly observed in hypertrophic cardiomyopathy. We report a rare case of subaortic stenosis associated with SAM, which was caused by cleft anterior mitral leaflet and an accessory papillary muscle. Surgical treatment was successful, and there were no complications.

Clinical results of staged repair with complete unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

OBJECTIVE: Our treatment strategy for pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collateral arteries is a staged repair that comprises the first complete unifocalization (UF) with 'unification' of intrapulmonary arteries and then the definitive repair. The purpose of this study is to evaluate the outcome of our staged repair strategy with complete UF and to determine the results of our current management strategy. METHODS: From 1982 to 2004, 113 consecutive patients were treated with staged repair at our institute. We evaluated the risk of definitive repair failure or death in the 3 years after definitive repair using logistic regression. Furthermore, we compared the early group (patients who underwent UF before December 1995) and the late group (patients who underwent UF after January 1996). RESULTS: The mean follow-up interval was 8.8 years (0.8 months to 23.3 years), and Kaplan-Meier-estimated overall survival rates after first UF were 80.9, 73.8, and 69.9% at 5, 10, and 15 years, respectively. Survival in patients with an absent central pulmonary artery (PA) was significantly lower than in those with a central PA (p<0.05), and the factor that was significantly associated with definitive repair failure or death in the 3 years after definitive repair was central PA morphology (p<0.05). Higher mean PA pressure after UF was detected in patients with hypoplastic central PA, compared with those without hypoplastic PA (30.9 mmHg vs 23.3 mmHg, p<0.05). In the late group, age (in years) at first UF (3.9 vs 8.4, p<0.01), second UF (4.3 vs 9.2, p<0.01), and definitive repair (5.8 vs 9.1, p<0.01) was significantly younger than in early group, and the survival rate after first UF in the late group was 96.2 and 91.3% at 3 and 7 years, respectively. Systolic right ventricular pressure and the pressure ratio between the right and the left ventricles after definitive repair in the late group were significantly lower than in the early group (53.6 mmHg vs 75.0 mmHg, p<0.01; 61.7% vs 75.9%, p<0.05). CONCLUSIONS: Hypoplastic central PA was a significant risk factor in this disease. The overall survival was improved by our current management strategy. Improved RV pressure after definitive repair appears to affect the long-term outcome.

Evaluation of tissue-engineered vascular autografts.

This study evaluated the endothelial function and mechanical properties of tissue-engineered vascular autografts (TEVAs) constructed with autologous mononuclear bone marrow cells (MN-BMCs) and a biodegradable scaffold using a canine inferior vena cava (IVC) model. MN-BMCs were obtained from a dog and seeded onto a biodegradable tubular scaffold consisting of polyglycolide fiber and poly(L-lactide-co-epsilon-caprolactone) sponge. This scaffold was implanted in the IVC of the same dog on the day of surgery. TEVAs were analyzed biochemically, biomechanically, and histologically after implantation. When TEVAs were explanted and stimulated with acetylcholine at 1 month, they produced nitrates and nitrites dose dependently. N(G)-nitro-L-arginine methylester significantly inhibited these reactions. With stimulation by acetylcholine, factor VIII-positive cells of TEVAs produced endothelial nitric oxide synthase proteins, and the ratio of endothelial nitric oxide synthase/s17 mRNA was similar among native IVC and TEVAs 1 and 3 months after implantation. TEVAs had biochemical properties and wall thickness similar to those of native IVC at 6 months after implantation, and tolerated venous pressure well without any problems such as calcification. The number of inflammatory cells in TEVAs and the ratio of CD4/s17 mRNA decreased significantly with time. These results indicate that TEVAs are a biocompatible material with functional endothelial cells and biomechanical properties and do not have unwanted side effects.

First evidence that bone marrow cells contribute to the construction of tissue-engineered vascular autografts in vivo.

BACKGROUND: Materials commonly used to repair complex cardiac defects lack growth potential and have other unwanted side effects. We designed and tested a bone marrow cell (BMC)-seeded biodegradable scaffold that avoids these problems. METHODS AND RESULTS: To demonstrate the contribution of the BMCs to histogenesis, we labeled them with green fluorescence, seeded them onto scaffolds, and implanted them in the inferior vena cava of dogs. The implanted grafts were analyzed immunohistochemically at 3 hours and subsequently at 2, 4, and 8 weeks after implantation using antibodies against endothelial cell lineage markers, endothelium, and smooth muscle cells. There was no stenosis or obstruction caused by the tissue-engineered vascular autografts (TEVAs) implanted into the dogs. Immunohistochemically, the seeded BMCs expressing endothelial cell lineage markers, such as CD34, CD31, Flk-1, and Tie-2, adhered to the scaffold. This was followed by proliferation and differentiation, resulting in expression of endothelial cells markers, such as CD146, factor VIII, and CD31, and smooth muscle cell markers, such as alpha-smooth muscle cell actin, SMemb, SM1, and SM2. Vascular endothelial growth factor and angiopoietin-1 were also produced by cells in TEVAs. CONCLUSIONS: These results provide direct evidence that the use of BMCs enables the establishment of TEVAs. These TEVAs are useful for cardiovascular surgery in humans and especially in children, who require biocompatible materials with growth potential, which might reduce the instance of complications caused by incompatible materials and lead to a reduced likelihood of further surgery.

The tissue-engineered vascular graft using bone marrow without culture.

OBJECTIVE: To overcome the shortcomings of current vascular grafts, tissue-engineering methods have been applied to cardiovascular regions. We previously reported the creation of a tissue-engineered vascular graft by using vascular mixed cells. However, the cost and manpower for harvesting and culturing the cells was too burdensome. To overcome these drawbacks, we have developed a new method for creating a tissue-engineered vascular graft by using bone marrow cells, which can be obtained easily and used immediately, without cell culture. METHODS: Biodegradable polymers seeded with different types of cells (group V, cultured venous cells; group B, bone marrow cells without culture; and group C, non-cell-seeded graft [as control]) were implanted into the inferior venae cavae of dogs. The grafts were explanted at 4 weeks and assessed histologically and biochemically. RESULTS: In the histologic examination, a regular layer of Masson-staining collagen fiber and a layer of factor VII-stained endothelial and ant-alpha-smooth muscle cell antigen-immunoreactive cells stained in groups V and B like native vascular tissue, whereas no such stained regular lining was detected in group C. A 4-hydroxyproline assay in group C showed significantly lower levels than in groups V and B or native tissue ( P < .05). The DNA content of the tissue-engineered vascular graft tended to be higher in group C than in groups V and B or in native tissue. CONCLUSIONS: In the creation of tissue-engineered vascular grafts, the method of using bone marrow cells seems to be useful and superior to that of using vascular cells because bone marrow cells can be used directly, without culture.

Midterm clinical result of tissue-engineered vascular autografts seeded with autologous bone marrow cells.

OBJECTIVE: Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source. The aim of the study was to assess the safety and feasibility of this technique for creating vascular tissue under low-pressure systems such as pulmonary artery or venous pressure. METHODS: Since September 2001, tissue-engineered grafts seeded with autologous bone marrow cells have been implanted in 42 patients. The patients or their parents were fully informed and had given consent to the procedure. A 5-mL/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. The polymer tube serving as a scaffold for the cells was composed of a copolymer of l -lactide and -caprolactone (50:50). This copolymer is degraded by hydrolysis. The matrix is more than 80% porous, and the diameter of each pore is 20 to 100 microm. Polyglycolic acid woven fabric with a thickness of 0.5 mm was used for reinforcement. Twenty-three tissue-engineered conduits (grafts for extracardiac total cavopulmonary connection) and 19 tissue-engineered patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median 5.5 years). All patients underwent a catheterization study, computed tomographic scan, or both, for evaluation after the operation. The patients received anticoagulation therapy for 3 to 6 months after surgery. RESULTS: Mean follow-up after surgery was 490 +/- 276 days (1.3-31.6 months, median 16.7 months). There were no complications such as thrombosis, stenosis, or obstruction of the tissue-engineered autografts. One late death at 3 months after total cavopulmonary connection was noted in patient with hypoplastic left heart syndrome; this was unrelated to the tissue-engineered graft function. There was no evidence of aneurysm formation or calcification on cineangiography or computed tomography. All tube grafts were patent, and the diameter of the tube graft increased with time (110% +/- 7 % of the implanted size). CONCLUSION: Biodegradable conduits or patches seeded with autologous bone marrow cells showed normal function (good patency to a maximum follow-up of 32 months). As living tissues, these vascular structures may have the potential for growth, repair, and remodeling. The tissue-engineering approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. Longer follow-up is necessary to confirm the durability of this approach.

Successful application of pulmonary arterial patch for coronary angioplasty late after arterial switch operation.

Pulmonary artery is infrequently utilized as a material for coronary patch angioplasty in children. We applied a pulmonary arterial patch for coronary angioplasty on an 8-year-old boy with total occlusion of the left main coronary artery late after an arterial switch operation. The pulmonary arterial patch was easy to handle and the immediate result after the operation was satisfactory.

The influence of pH strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease: results of a randomized trial and real-time monitoring.

OBJECTIVE: The optimal pH strategy during hypothermic cardiopulmonary bypass remains controversial. Systemic pulmonary collateral circulation may develop in patients with cyanotic anomalies. The purpose of this study was to evaluate the effect of pH strategies on cerebral oxygenation and systemic pulmonary collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. METHODS: Forty cyanotic patients (age > 1 year) with heart disease were prospectively randomized into 2 groups. Group 1 (n = 19, 14.3 +/- 1.5 kg) underwent hypothermic cardiopulmonary bypass with alpha-stat strategy and group 2 (n = 21, 12.5 +/- 0.9 kg) with pH-stat. Cardiopulmonary bypass was established with pump-assisted drainage. Cerebral oxygenation was assessed by near-infrared spectroscopy and the systemic pulmonary collateral circulation was calculated by pump flows [% systemic pulmonary collateral circulation = perfusion flow - drainage flow)/perfusion flow x 100]. Lactate was measured as an index of systemic anaerobic metabolism. RESULTS: There were no significant differences in preoperative hematocrit, oxygen saturation, Qp/Qs, cardiopulmonary bypass duration, minimum temperatures, perfusion flow and pressure, urine output, and depth of anesthesia between the groups. Oxyhemoglobin signal and tissue oxygenation index of near-infrared spectroscopy monitoring were significantly lower in group 1 compared with group 2 (P =.008 and P <.0001, respectively), suggesting inadequate cerebral oxygenation with alpha-stat. Deoxygenated hemoglobin signal was significantly higher in group 1 relative to group 2 (P <.0001). The % systemic pulmonary collateral circulation was significantly lower in group 2 compared with group 1, suggesting a reduced pulmonary collateral circulation with pH-stat (P <.0001, average; group 1, 20.1% +/- 1.2%; group 2; 7.7% +/- 0.7%). Serum lactate was significantly lower in group 2 (P <.0001). CONCLUSIONS: The pH-stat strategy results in an improved environment, including sufficient cerebral oxygenation, decreased systemic pulmonary collateral circulation, and lower lactate level during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. Future studies should investigate the long-term neurological outcome.

Extracardiac total cavopulmonary connection using a tissue-engineered graft.

OBJECTIVE: Extracardiac and lateral tunnel total cavopulmonary connection are currently 2 major options for patients with a single ventricle physiology. However, each procedure has some disadvantages over the other. We developed a new technique of extracardiac total cavopulmonary connection using a tissue-engineered graft to overcome some of the disadvantages previously associated with both the extracardiac and lateral tunnel procedures. METHODS: Between February 2001 and October 2002, 8 patients underwent an extracardiac total cavopulmonary connection using a tissue-engineered graft in our institution. Collected bone marrow cells (1 x 10(8) mononucleocytes) from a patient (approximately 1-4 mL/kg body weight) were seeded onto a biodegradable scaffold composed of polycaprolactone-polylactic acid copolymer reinforced with woven polylactic acid. After a 2- to 4-hour cultivation, the seeded scaffold was implanted as an extracardiac conduit during the total cavopulmonary connection operation. RESULTS: There were no hospital or late deaths. At a mean follow-up of 13.4 months (range 4-25 months), all patients are alive and asymptomatic with no need for repeat surgery. A postoperative catheter examination or computed tomography showed all tissue-engineered grafts to be patent and revealed no stenosis, obstruction, or aneurysmal change in the 8 patients. CONCLUSION: We believe that extracardiac total cavopulmonary connection using a tissue-engineered graft has the potential to overcome some of the disadvantages previously associated with extracardiac or lateral tunnel total cavopulmonary connection. However, an extended follow-up period is required to clarify the long-term clinical outcome for the tissue-engineered graft.

Successful application of tissue engineered vascular autografts: clinical experience.

Foreign materials often used in cardiovascular surgery may cause unwanted side effects and reduced growth potential. To resolve these problems, we have designed a tissue-engineering technique that utilizes bone marrow cells (BMCs) in clinical treatments. To obtain tissue-engineered material, we harvested saphenous vein samples from patients, which were then minced, cultured and seeded onto a biodegradable scaffold. The first operation was performed in May 1999 as previously described (N. Engl. J. Med. 344 (7) (2001) 532) and this method was repeated on two other patients. From November 2001, we used aspirated BMCs as the cell source, which were seeded onto the scaffold on the day of surgery. This method was applied in 22 patients. There was no morbidity such as thrombogenic complications, stenosis or obstruction of tissue-engineered autografts, and no mortality due to these techniques. These results indicate that BMCs seeded onto a biodegradable scaffold to establish tissue-engineered vascular autografts (TEVAs) is an ideal strategy, and present strong evidence for the justification and validity of our protocol in clinical trials of tissue engineering.

Surgery for unilateral absence of pulmonary artery using autologous tissue.

A 7-year-old girl with unilateral absence of the pulmonary artery underwent autologous tissue limited reconstructive surgery. The proximal portion of the artery was reconstructed by rotating a reverse U-shaped cut opposite the pulmonary arterial wall and covering the anterior surface with autologous pericardium. Follow-up catheterization at 5.8 years after surgery revealed no stenosis. This procedure could become one of the preferred methods for this unusual clinical condition.

Effects of autologous platelet concentrate reinfusion after open heart surgery in patients with congenital heart disease.

BACKGROUND: Plasma pheresis and reinfusion of platelet-rich plasma has not been shown to reduce blood loss in cardiac patients. Recently, freshly prepared autologous platelet concentrates (PC) can be made from patient's blood and has a higher concentration than conventional platelet rich plasma. In this study, the effects of autologous PC reinfusion were examined after open heart surgery in patients with congenital heart disease. METHODS: Eight patients with noncyanotic congenital heart disease, who underwent open heart surgery and reinfusion of autologous PC, were classified as the PC group. Eight other patients with noncyanotic congenital heart disease, who underwent only open heart surgery, were defined as the control group. Ages ranged from 2 to 24 years and were not significantly different between the two groups (9.3 +/- 5.1 years in the PC group and 12.6 +/- 7.9 years in the control group, p = 0.33). In the PC group, blood was collected from the femoral vein through a 6F catheter introducer; 9 to 20 U (13.0 +/- 5.4 U, 0.42 +/- 0.22 U/kg) of autologous PC were prepared and were reinfused after protamine administration. The time course of platelet counts was examined until postoperative day 7. Aggregation responses to adenosine diphosphate; (4 micromol/L and 8 micromol/L), collagen (1 micromol/L and 5 micromol/L), and epinephrine (5 micromol/L and 10 micromol/L) were evaluated after induction of anesthesia (individual references), after protamine administration, at the end of the operation; these responses were shown as recovery ratios. RESULTS: Blood loss during surgery in the PC group was significantly less than in the control group (4.8 +/- 3.0 mL/kg versus 7.8 +/- 1.7 mL/kg, p = 0.044). Similarly blood loss on postoperative day 1 in the PC group was significantly less than in the control group (3.6 +/- 1.2 mL/kg versus 7.2 +/- 3.1 mL/kg, p = 0.013). The platelet counts in the PC group were larger than those in the control group until postoperative day 5, after reinfusion of prepared autologous PC. The recovery ratios of the aggregation responses to adenosine diphosphate, collagen, and epinephrine after protamine administration were not significantly different between the two groups. However, recovery in the PC group after reinfusion of the prepared autologous PC was greater than in the control group. CONCLUSIONS: Reinfusion of the freshly prepared autologous PC was followed by good aggregation responses and low blood loss in patients with noncyanotic congenital heart disease after open heart surgery. This procedure may be useful in pediatric open heart surgery without blood transfusion or with little administration of homologous blood products.

Valvular repair for atrioventricular regurgitation in complex anomalies in modified Fontan procedure with reference to a single ventricle associated with a common atrioventricular valve.

Between January 1985 and October 1998, 169 of 372 patients who underwent a modified Fontan procedure had atrioventricular valve regurgitation (AVVR) that ranged in degrees from 1 to 4. Concomitant repair for AVVR was performed in the majority of cases. All but 12 patients had the AV valve repaired, mainly by circular annuloplasty; none had valve replacement. Although mortality was significantly higher in the AVVR cases (21 of 169 [12%]) than in the cases without AVVR (eight of 203 [3.9%]; P <.007, chi-square), actuarial survival in the AVVR cases was 83% at 5 years, 81% at 10 years, and 73% at 12 years. The degree of AVVR before surgery was 1.62 +/- 0.73 on average; 82 cases had more than grade 2 regurgitation. There was a significant decrease to 0.54 +/- 0.61 (P <.0001) after surgery in long-term survivors. Cases with AVVR can be treated with reasonable risk provided proper repair of the valve is performed. Circular annuloplasty is a simple and uniformly effective method with which to control regurgitation, even for the common AV valve. Copyright 1999 by W.B. Saunders Company