Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts.

Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionality, the grafts were implanted as inferior vena cava interpositional conduits in mice. Modified vascular grafts displayed increased endothelial cell attachment and activity in vivo, according to microscopy techniques, histological results, and eNOS expression. Inner lumen diameter of the modified grafts was also better maintained than controls. Overall, while both functionalized grafts outperformed the unmodified control, grafts modified with anti-CD34Ab appeared to yield the most improved results compared to VEGF-loaded grafts.

Transforming growth factor beta expression by human vascular cells inhibits interferon gamma production and arterial media injury by alloreactive memory T cells.

Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)-γ and IL-17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF-ß, by regulatory lymphocytes is known to inhibit both the differentiation of naïve T cells into effector T cells and the development of arteriosclerosis in murine models. We investigated the role of TGF-ß on the alloreactivity of human effector memory T cells (Tem). Quiescent vascular cells, but not Tem, expressed TGF-ß. Blockade of TGF-ß activity in cocultures of CD4(+) Tem with allogeneic endothelial cells significantly increased IFN-γ, but not IL-17, secretion. Additionally, serologic neutralization of TGF-ß in immunodeficient mouse hosts of human coronary artery grafts into which allogeneic human T cells were adoptively transferred resulted in heavier medial infiltration by Tem, greater loss of medial smooth muscle cells and increased IFN-γ production within the grafts without significantly reducing either intimal injury or IL-17 production. Protective effects of TGF-ß may be limited by fewer TGF-ß-expressing vascular cells within the intimal compartment, by a reduction in the expression of TGF-ß by vascular cells in rejecting grafts, or possibly to less effective suppression of Tem than naïve T cells.

[Ross procedure with aortic replacement for aortic stenosis with ascending aortic aneurysm: report of a case].

Bicuspid aortic valve (BAV) is a common congenital heart disease, and it is well known to be a risk factor for ascending aortic dilatation and dissection. We here report a case of 34-year-old woman who underwent Ross procedure with ascending aortic replacement under the diagnosis of subaortic stenosis and ascending aortic aneurysm. She was pointed out to have heart murmur soon after the birth diagnosed as patent ductus arteriosus. The ductus was ligated when she was 3-years-old, however, heart murmur remained. Further examinations revealed that she also had aortic stenosis with BAV. During her 20-year-follow-up, subaortic stenosis and ascending aorta ectasia were also progressed. Pathological examinations of resected ascending aortic wall showed mucoid degeneration and laceration of collagen fibers, suggesting the fragility of dilated aortic wall with BAV.

Callus formation during healing of the repaired tendon-bone junction. A rat experimental model.

This study was undertaken to elucidate the mechanism of biological repair at the tendon-bone junction in a rat model. The stump of the toe flexor tendon was sutured to a drilled hole in the tibia (tendon suture group, n = 23) to investigate healing of the tendon-bone junction both radiologically and histologically. Radiological and histological findings were compared with those observed in a sham control group where the bone alone was drilled (n = 19). The biomechanical strength of the repaired junction was confirmed by pull-out testing six weeks after surgery in four rats in the tendon suture group. Callus formation was observed at the site of repair in the tendon suture group, whereas in the sham group callus formation was minimal. During the pull-out test, the repaired tendon-bone junction did not fail because the musculotendinous junction always disrupted first. In order to understand the factors that influenced callus formation at the site of repair, four further groups were evaluated. The nature of the sutured tendon itself was investigated by analysing healing of a tendon stump after necrosis had been induced with liquid nitrogen in 16 cases. A proximal suture group (n = 16) and a partial tenotomy group (n = 16) were prepared to investigate the effects of biomechanical loading on the site of repair. Finally, a group where the periosteum had been excised at the site of repair (n = 16) was examined to study the role of the periosteum. These four groups showed less callus formation radiologically and histologically than did the tendon suture group. In conclusion, the sutured tendon-bone junction healed and achieved mechanical strength at six weeks after suturing, showing good local callus formation. The viability of the tendon stump, mechanical loading and intact periosteum were all found to be important factors for better callus formation at a repaired tendon-bone junction.

[Partial anomalous pulmonary venous connection to the high portion of the superior vena cava associated with ventricular septal defect repaired with williams method using right atrial flap: report of a case].

A 3-year-old boy suffered from the poor body weight gain under the diagnosis of partial anomalous pulmonary venous connection (PAPVC) to the high portion of the superior vena cava (SVC) associated with ventricular septal defect (VSD) and intact atrial septum (IAS). Preoperative cardiac catheterization revealed the pulmonary to systemic flow ratio 2.6 and mean pulmonary arterial pressure of 21 mmHg. He successfully underwent surgical repair with Williams method using right atrial (RA) flap out and VSD patch closure. Postoperative course was uneventful and echocardiography demonstrated no obstruction at the both routes of neo-SVC and neo-right upper pulmonary venous return.

3D-Printed Biodegradable Polymeric Vascular Grafts.

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth.

[Aortic valve replacement for the patient with Osler-Rendu-Weber disease].

Osler Rendu-Weber (O-R W) disease (hereditary haemorrhagic telangiectasia) is characterized by an anormality of the peripheral blood vessels which often causes recurrent epistaxis. We presented a case of aortic valve replacement for the patient with O-R-W disease. A 75-year-old woman diagnosed as O-R-W disease with chest pain and dyspnea was admitted. Preoperative transthoratic echocardiography showed severe aortic valve stenosis (AS) with a pressure gradient (from left ventricle to ascending aorta) of 72.5 mmHg. Urgent aortic valve replacement (AVR) was performed after preoperative hormonal (estrogen-progesterone) therapy, that might be effective for bleeding from vascular ectasia. No hemorrhagic tendency was recognized and the postoperative course was uneventful.

[Comparison of right ventricular function between prevention and enlargement of pulmonary valve annulus after repair of tetralogy of Fallot; mid-term results].

Total of 41 patients with tetralogy of Fallot (TOF) who underwent intracardiac repair from 1993 to 1998 were divided into 2 groups: preservation (n = 14) or enlargement (n = 27) of the pulmonary valve annulus. The procedure was decided on the Z value of the annular size: above or under -2 SD of the standard value. Although postoperative right ventricular (RV) diastolic volume (RVEDV) and cardiothoracic ratio (CTR) were larger than the preservation group and pulmonary regurgitation (PR) existed in the enlargement group, RV pressure was decreased and central venous pressure (CVP) was low and RV contraction was preserved. The exercise capacity was also good and no significant arrhythmia was recognized. Our mid-term results showed that appropriate enlargement of the pulmonary valve annulus preserved good RV function in patients with TOF.

[Differences in postoperative course by preoperative left ventricular volume after closure of ventricular septal defect during early infancy].

A total of 38 early infants with ventricular septal defect (VSD) were divided into 2 groups by preoperative LVEDV. The group A (n=14, LVEDV>250% N) showed significantly longer period of intubation, cathecholamine drip, and hospitalization compared with the group B (n=28, LVEDV<250% N). At dischage, both groups showed significant lowered right ventricular (RV) pressure, but LVSF in the group A was significantly lower than that in the group B. The patients with larger left ventricular (LV) volume preoperatively were thought to be potential high-risk groups in cardiac and pulmonary function and their postoperative course was prolonged and recovery of LV function was worse. In such patients, special care is mandatory to do postoperative management and to decide timing of operation.

Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model.

Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.

Double switch operation for superior-inferior ventricles.

Superior-inferior ventricles are a rare cardiac malformation characterized by the two ventricles lying one above the other instead of side by side. Consequently, the interventricular septum that separates such ventricles is horizontal, and anomalies of the atrioventricular valves and the ventriculoarterial relations are almost always present. This complex anomaly is difficult to manage with an operation, so few cases have been reported. We describe a successful experience in which we performed a double switch operation, consisting of the Senning and Jatene procedures, for this rare malformation accompanied by double-outlet right ventricle [S,L,L]. This is the first report we have been able to locate of a double switch operation for superior-inferior ventricles.

[Aneurysm of the noncoronary sinus of valsalva associated with aortic regurgitation: report of a case].

A 39-year-old man has complained of palpitation and dyspnea since 8 months ago. With aortic regurgitation pointed out in another hospital, he was referred to our hospital for examination. Preoperative ultracardiography (UCG) showed a dilated noncoronary sinus of Valsalva and aortic regurgitation. A daughter aneurysm was found by aortography. There were 2 perforations and 1 pouch at the noncoronary sinus cusp (NCC). The noncoronary sinus of Valsalva was dilated and the orifice to the daughter aneurysm was noticed. The noncoronary sinus of Valsalva was obliterated by suturing a dacron patch on the orifice. The aortic valve was replaced with ATS 23 mm valve. Postoperative computed tomography (CT) showed clot formation outside the patch.

[A study of isolated tricuspid valve surgery late after left heart valve operation].

Management of severe tricuspid regurgitation late after left heart valve operation is controversial. There has been reluctance to the operation due to the high risk of repeat operation, coexistent right ventricular dysfunction and pulmonary hypertension. We investigated 6 cases of isolated tricuspid valve surgery (tricuspid valve replacement: 2, tricuspid valve plasty: 4) late after left heart valve operation. Before operation, these patients showed poor general condition (4 cases were NYHA III or IV) but good left ventricular function [mean ejection fraction (EF) 66 +/- 9.6%]. Hospital mortality was 0% and the mean mid-term actual event-free survival over 2 +/- 1.8 years was 80%. Most of patients demonstrated NYHA I and improvement of hepatomegaly after operation. There were many complications in 2 cases that had been performed previous operation more than 20 years before. In summary, the patient who complained symptoms due to right heart ventricular failure and showed good left ventricular function after left heart valve surgery should be considered to undergo tricuspid valve operation before the occurrence of other complications.

[Surgery for distal aortic arch aneurysm with a patent left internal mammary-to-coronary artery graft; report of a case].

We report a case of 62-year-old male who suffered from a distal aortic arch aneurysm developed 5 years after coronary artery bypass grafting (CABG). Preoperative angiography revealed a distal arch aneurysm and a patent left internal mammary artery (LIMA) graft. Graft replacement of the total aortic arch was performed using a 4 branched graft. After the re-median sternotomy, cardiopulmonary bypass was established with ascending aortic perfusion and right atrium (RA) drainage. Myocardial protection was achieved with root cold blood cardioplegia and LIMA continuous cold blood perfusion. Distal anastomosis was performed under selective cerebral perfusion and during deep hypothermic circulatory arrest. Postoperative course was satisfactory and the patient was discharged without complications.

[The effect of milrinone administrated before weaning from cardiopulmonary bypass in adult cardiac surgery].

We investigated the effect of milrinone (phoshphodiesterase III inhibitor) on postoperative hemodynamics in adult eighteen cardiac surgical patients (mean LVEF = 63%). Milrinone was administrated just after the aortic declamping during CPB. Comparing with control group, systemic vascular resistance decreased significantly and sufficient inotropic effect was sustained. In order to keep proper blood pressure much more cathechoramine dose was need when milrinone dose increased during this study. This is supposed that milrinone affected strong vasodilating effect and caused relative hypovolemic condition to the patient who showed good cardiac function. Milrinone causes best efficacy to the patient of poor cardiac function when he showed deconpensation or relatively hypervolemic hemodynamic condition.

[Cryopreservation of vascular mixed cell for tissue engineering in cardiovascular surgery].

Tissue engineering (TE) is a new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymer scaffold. Various vascular and valvular grafts have been tried to create with this TE approach. In clinical use of this technique, harvested and cultured cells have to keep viability until implantation as tissue engineered tissue. But few research for cryopreservation of vascular mixed cells has been performed. So, we investigated the proper method for cryopreservation of vascular mixed cells harvested from femoral artery and vein of dogs. Cells were cultured and divide into three groups, A: cryopreserving in 5% dimethylsulfoxide (DMSO), hydroxyethyl starch (HES), and fetal bovine serum (FBS) with -80 degrees C freezer; B: cryopreserving in 10% DMSO and FBS with programmed freezer; C: control (continuous culture in media). After rapid thawing at 40 degrees C, group A showed higher viability than group B with flow cytometry. The results means that vascular mixed cells can be successfully cryopreserved in the DMSO/HES mixture simply and inexpensively, without rate controlled freezing.

[Congenital supravalvular aortic stenosis; report of a case].

We experienced a successful surgical case of extended aortoplasty by means of Doty's method (two sinus reconstruction) for congenital supravalvular aortic stenosis (SAS). Case was 12-year-old boy, who had no complaint except heart murmur. The retrograde aortography demonstrated localized stenosis just above the aortic valve, and it was an hour-glass type. The preoperative peak systolic pressure gradient between the left ventricle and ascending aorta was 56 mmHg, which was improved postoperatively. This case showed excellent results. Doty's aortoplasty was favorable method for SAS without deformity of aortic valve and coronary obstruction.

[A case report of a coronary fistula from left coronary artery to left ventricle].

The patient is a 44-year-old man. He has had chest pain on effort since 1994, diagnosed as unstable angina in 1996. He was found to have three vessel disease on coronary angiography and was sent to TWMC for operation. CABG was performed for the right and left anterior descending arteries, and TMLR for the posteroinferior region because the left circumflex artery was fine and ungraftable. Both the grafts were patent and there was improved LV function. Interestingly, we found a coronary fistula running from the left coronary artery to the left ventricle. As far as we can tell from our literature searches, this is the first time that a coronary fistula has been found after TMLR.

[Total anomalous of pulmonary venous connection in infants less than 3 months old].

We examined the surgical results of total anomalous pulmonary venous connection (TAPVC) retrospectively in 6 infants, who were less than 3 months old and underwent a total repair at Ehime Prefectural Central Hospital between May, 1993 through May, 1998, in terms of the pre, peri, and postoperative management, the site of connection, and the surgical procedures. Aged at operation ranged from 1 day to 86 days (mean 39 days), and body weight ranged from 2.4 kg to 5.5 kg (mean 3.4 kg). All 6 patients had echocardiographic diagnosis and cardiac catheterization but one. In operative procedure, cut back method was done in a patient of paracardiac type of Darling's classification and posterior approach was used in total correction for 4 supracardiac and 1 infracardiac type. There were 3 hospital deaths who had poor conditions before operation, but no late deaths. Surgical results of TAPVC might have been improved with advances in non-invasive diagnosis by echocardiography, and pre and perioperative management. And we should take care of these patients of TAPVC in long term period to make sure that they have no pulmonary venous obstruction.