[Reconstruction of pulmonary blood flow in the Norwood procedure; Blalock-Taussig shunt; from bench to surgery].

Although the right-ventricle to pulmonary artery( RV-PA) shunt as a source of pulmonary blood supply of Norwood procedure has improved early outcomes, disadvantages including right ventricular dysfunction or arrhythmias have been reported. So it has been still remained controversial whether BT shunt or RV-PA conduit should be selected. We examined the influence of Blalock-Taussig( BT) shunt size on regulation of the pulmonary blood flow in experimental model of a univentricular heart to determine the specific guidelines regarding suitable shunt size in the Norwood procedure. The canine univentricular heart model with the ratio of shunt size to body weight (SS/BW) of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio( Qp/Qs)and arterial PCo2, but those with SS/BW of 1.1 to 1.4 did not. Similar phenomena were shown with the grouped data on relationship between the Qp/Qs and inspired oxygen fraction. These findings imply that when SS/BW is 0.8 to 1.1, the Qp/Qs is controllable by physiologic respiratory manipulations. In the context of our clinical experiences, SS/BW of 0.9 to 1.0 is considered a useful index for suitable BT shunt in the Norwood procedure.

Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.

BACKGROUND AND OBJECTIVES: To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact. METHODS: Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated. RESULTS: The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy. DISCUSSION: Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.

Development of acquired intrapulmonary venous anastomosis contributing to establishment of Fontan circulation.

Pulmonary venous (PV) obstruction is associated with a poor prognosis, as well as a high risk of recurrence, following surgical treatment. It can also interfere with the successful completion of Fontan circulation in patients with complex congenital heart disease. A case of a patient who had right isomerism (also known as asplenia syndrome), total anomalous pulmonary venous connection (TAPVC), and a single right ventricle is presented. Although bilateral total occlusion of the inferior PVs was identified postoperatively, the formation of the anastomosis and collateral vessels into the superior and middle PVs enabled successful completion of Fontan circulation. Anastomoses and collateral flow of the PVs were found largely in the interlobar pleura and not in the lung parenchyma.

Appropriate Surgical Treatment of Symptomatic Primary Varicose Veins Decreases Systemic Inflammatory Biomarkers.

Objective: To evaluate the relationship between systemic inflammatory biomarkers and efficacy of surgical treatment of primary varicose veins of the lower extremities. Methods: Total 12 patients who underwent endovenous laser ablation or stripping of varicose veins and six healthy subjects were enrolled. Structural and molecular changes of varices were assessed by immunohistochemical staining with anti-monocyte chemotactic protein-1 (MCP-1). MCP-1 and interleukin-6 (IL-6) levels in systemic antecubital blood were measured before and at 12 weeks after treatment. Results: Immunohistochemical staining revealed prominent manifestation of MCP-1-positive endothelial cells in the walls of varices. Preoperative serum MCP-1 and IL-6 levels in the patients were significantly higher than those in the control (166±12 pg/mL vs 99±10 pg/mL, p=0.003; 5.1±0.95 pg/mL vs 0.0±0.0 pg/mL, p=0.001, respectively). The values were significantly correlated with the severity of chronic venous insufficiency (CVI). Postoperative serum MCP-1 level significantly decreased compared with the preoperative level (152±10 pg/mL vs 166±12 pg/mL, p=0.048). The values after endovenous laser ablation did not significantly decrease compared with those after stripping. Conclusion: Varicose veins with CVI increase inflammatory biomarker levels in the local tissue and systemic blood. Appropriate treatment of symptomatic varicose veins decreases inflammatory biomarker levels.

Pseudoaneurysm of the thoracoabdominal aorta caused by a severe migration of an anterior spinal device.

BACKGROUND CONTEXT: Case report. PURPOSE: To describe the case of pseudoaneurysm of the thoracoabdominal aorta caused by the severe migration of an anterior spinal device 5 years after surgery. STUDY DESIGN/SETTING: Case report. METHODS: A 70-year-old woman was referred to us because of migrated anterior spinal devices and a pseudoaneurysm of the thoracoabdominal aorta. This patient had undergone anterior corpectomy and spinal fusion from Th12 to L2 because of delayed palsy after a burst fracture using a smooth rod Kaneda device (SRK) with bioactive ceramic (apatite-wollastonite containing glass ceramic) at a local hospital. She had persistent low back pain after the surgery. RESULTS: Five years after the initial surgery, the patient was referred to us because of increasing of her low back pain and the migrated SRK devices shown on plain X-ray films. An enhanced computed tomography scan taken in our hospital clearly showed a pseudoaneurysm of the thoracoabdominal aorta surrounding the SRK devices. The pseudoaneurysm was resected, the aortic defect was repaired with an artificial patch, and the migrated SRK devices were removed. CONCLUSIONS: The pseudoaneurysm of the aorta can occur secondary to a migrated anterior spinal fixation device and can be successfully treated by revision anterior surgery with vascular repair and implant removal.

A successful transatrial repair in redo surgery of postinfarction inferoposterior ventricular septal rupture.

A successful transatrial repair in redo surgery of postinfarction posterior ventricular septal rupture (VSR) was performed after an infarct exclusion technique through left ventriculotomy incision of the infarcted area. For the infarct lesion, this approach provides excellent results with sufficient closure of the VSR and prevention of the ventricular remodeling for five years. A right atrial approach for postinfarction posterior VSR is very useful for avoiding any further ventriculotomy in an already impaired ventricle, securing a stable suture, and preserving the left ventricular geometry and function.

Long-term Results After Open Mitral Commissurotomy for a One-Month-Old Infant With Mitral Stenosis.

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.

Effects of Transplanted Human Cord Blood-Mononuclear Cells on Pulmonary Hypertension in Immunodeficient Mice and Their Distribution.

OBJECTIVES: To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. METHODS: MCT was administered to BALB/c Slc-nu/nu mice, and PH was induced in mice 4 weeks later. Fresh hUCB-MNCs harvested from a human donor after her delivery were injected intravenously into those PH mice. The medial thickness of pulmonary arterioles, ratio of right ventricular to septum plus left ventricular weight (RV/S+LV), and ratio of acceleration time to ejection time of pulmonary blood flow waveform (AT/ET) were determined 4 weeks after hUCB-MNC transplantation. To reveal the incorporation into the lung, CMTMR-labeled hUCB-MNCs were observed in the lung by fluorescent microscopy. DiR-labeled hUCB-MNCs were detected in the lung and other organs by bioluminescence images. RESULTS: Medial thickness, RV/S+LV and AT/ET were significantly improved 4 weeks after hUCB-MNC transplantation compared with those in mice without hUCB-MNC transplantation. CMTMR-positive hUCB-MNCs were observed in the lung 3 hours after transplantation. Bioluminescence signals were detected more strongly in the lung than in other organs for 24 hours after transplantation. CONCLUSIONS: The results indicate that hUCB-MNCs are incorporated into the lung early after hUCB-MNC transplantation and improve MCT-induced PH. J. Med. Invest. 64: 43-49, February, 2017.

Efficacy and Optimal Timing of Endovascular Treatment for Type B Aortic Dissection.

OBJECTIVES: To determine the efficacy and the optimal timing of thoracic endovascular aortic repair (TEVAR) for closing the primary entry in uncomplicated patients with chronic type B aortic dissection and a patent false lumen (FL). METHODS: Thirteen patients underwent TEVAR for aortic dissection between 2008 and 2012. These patients had chronic dissection with a patent FL and expansion of the aorta. Early TEVAR was performed for five patients within 1-7 months from the index dissection (TEVAR-EC group) and delayed TEVAR was performed for eight patients within 1-16 years (TEVAR-DC group). Changes in the diameters and volumes of the true lumen (TL) and FL and the aortic remodeling were assessed by multidetector computed tomography for 3 years after TEVAR. RESULTS: The reduction rate of FL in the thoracic aorta was notably higher in the TEVAR-EC group than in the TEVAR-DC group regardless of the presence or absence of distal retrograde flow. There was a significant TL expansion despite different timings of TEVAR. CONCLUSIONS: Early TEVAR resulted in good prognosis and preferable aortic remodeling in uncomplicated patients with chronic type B aortic dissection and a patent FL, and we recommend early TEVAR within seven months after the index dissection.

Suitable shunt size for regulation of pulmonary blood flow in a canine model of univentricular parallel circulations.

OBJECTIVE: We examined the influence of shunt size on regulation of the pulmonary blood flow in a canine model of a univentricular heart because specific guidelines regarding suitable shunt size in the Norwood operation remain undetermined. METHODS: Beagle dogs (n = 8) 3 to 7 months old and weighing 3.0 to 5.0 kg were used. Atrial septectomy and patch closure of the tricuspid valve were performed, and a systemic-pulmonary arterial shunt was created by interposing a 3.5- or 4.0-mm graft between the right subclavian artery and main pulmonary artery. After cardiopulmonary bypass, hemodynamic variables including pulmonary and systemic blood flow were measured consecutively according to physiologically respiratory manipulations. The ratio of shunt size to body weight ranged from 0.80 to 1.33 mm/kg (1.08 +/- 0.16 mm/kg). RESULTS: Each dog with a ratio of shunt size to body weight of 0.8 to 1.1 showed significant negative correlation between the pulmonary/systemic blood flow ratio and arterial Pco(2), but those with a ratio of shunt size to body weight of 1.1 to 1.4 did not. Consequently each dog with a ratio of shunt size to body weight of 0.8 to 1.0 got adequate systemic flow, whereas a ratio of 1.0 to 1.4 resulted in inadequate systemic flow and acidic status. Similar phenomena were shown with the grouped data on relationship between the pulmonary/systemic blood flow ratio and inspired oxygen fraction. CONCLUSIONS: These findings imply that when the ratio of shunt size to body weight is 0.8 to 1.1, the pulmonary/systemic blood flow ratio is controllable by physiologic respiratory manipulations. Larger shunts make pulmonary blood flow excessive and uncontrollable. We recommend that a ratio of shunt size to body weight of 0.9 to 1.0 be considered a useful index for suitable systemic-pulmonary arterial shunt in the Norwood operation.

Iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass.

It may be difficult to access a route to deliver a stent-graft for abdominal aortic aneurysm in high-risk patients with bilateral iliofemoral occlusive disease. These two patients underwent both endovascular aortic aneurysm repair by a modified iliac access conduit technique and sequential ipsilateral iliofemoral artery bypass using the conduit, which provided excellent results. The iliac access conduit facilitates endovascular aortic aneurysm repair and ipsilateral iliofemoral bypass of high-risk patients with abdominal aortic aneurysm and bilateral iliofemoral occlusive disease.

Techniques and results in the management of multiple muscular trabecular ventricular septal defects.

The management of patients with multiple muscular trabecular ventricular septal defects (VSDs) remains controversial. In the past two decades, innovative techniques including a right ventricular apical infundibulotomy and transcatheter, intraoperative and perventricular device closure have been exploited, and essential right atrial approach and limited apical left ventriculotomy have also been refined. However, specific management guidelines for this difficult disease have not been established. In this article, the benefits and drawbacks of each technique are reviewed and discussed. Primary repair for infants with multiple muscular trabecular VSDs was associated with good late outcomes. The right atrial approach was satisfactory for all muscular VSDs, excluding apical defects that were well seen through a limited apical ventriculotomy. Surgical closure of apical defects could be achieved safely and completely in early infancy through a limited apical left ventriculotomy or a right ventricular apical infundibulotomy. Further follow-up and prudent evaluations of ventriculotomy-associated morbidities are needed. Pulmonary artery banding should be limited to a small infant with complex associated defects. Percutaneous device closure, the most desirable option, is impractical due to limitations between the delivery system and access route. Intraoperative device closure appears less successful than device closure in the catheterization laboratory. Perventricular device closure has a significant advantage of being a non-bypass procedure approach. A less invasive strategy for "true" Swiss cheese septum is needed. All may have an important role, and results obtained by using these techniques are encouraging. These hybrid approaches will promise future success on management guidelines of multiple muscular trabecular VSDs.

Delayed-onset severe heparin-induced thrombocytopenia after total arch replacement under cardiopulmonary bypass.

An extremely rare case with delayed-onset heparin-induced thrombocytopenia (HIT) is described. A 46-year-old man underwent arch replacement for aortic dissection under cardiopulmonary bypass and initial exposure of unfractionated heparin. In post operative 7 days, persistent atrial fibrillation was occurred, so a continuous infusion of heparin (10000 IU/day) and Vitamine K antagonist (Warfarin) taking was started for preventing thrombosis. By 32 days after the operation, his platelet count had fallen (3×10(3)/µL) and oral hematoma and ecchymoma of bilateral lower legs were occurred. The value of HIT antibodies and the IgG antibody was 2.485 and 1.586 on 32-postoperative day, respectively. Heparin was immediately discontinued, and argatroban administrated. Platelet exceeded above 100×10(3)/µL on 12 days of the therapy. To our knowledge, few cases of delayed-onset severe HIT associated with CPB surgery have been reported in Japan.

Usefulness of central venous oxygen saturation monitoring during bidirectional Glenn shunt.

A PediaSat™ oximetry catheter (PediaSat: Edwards Lifesciences Co., Ltd., Irvine, CA, U. S. A.), which facilitates continuous measurement of central venous oxygen saturation (ScvO2), may be useful for surgery for pediatric congenital heart disease. We used PediaSat during a bidirectional Glenn shunt. The patient was a 13-month-old boy. Under a diagnosis of left single ventricle (pulmonary atresia, right ventricular hypoplasia, atrial septal defect) and residual left aortic arch/left superior vena cava, a modified right Blalock-Taussig shunt was performed. Cyanosis deteriorated, so a bidirectional Glenn shunt was scheduled. After anesthesia induction, a 4.5 Fr double-lumen (8 cm) PediaSat was inserted through the right internal jugular vein for continuous ScvO2 monitoring. Furthermore, the probe of a near-infrared, mixed blood oxygen saturation-measuring monitor was attached to the forehead for continuous monitoring of the regional brain tissue mixed blood oxygen saturation (rSO2) (INVOS™ 5100C, Covidien; Boulder, CO, U. S. A.). Blockage of the right pulmonary artery and right superior vena cava decreased the oxygen saturation, ScvO2, and rSO2, but increased the central venous pressure. Although changes in ScvO2 were parallel to those in rSO2, the former showed more marked changes. A combination of ScvO2 and rSO2 for monitoring during Glenn shunt may be safer.

Autologous peripheral blood-derived mononuclear cells induced by erythropoietin improve critical ischemic limbs.

PURPOSE: Efficient and secure collection of CD34+ cells are crucial for the angiogenic therapies. We have developed autologous peripheral blood-mononuclear cell (MNC) transplantation induced by erythropoietin (rhEPO) for critical ischemic limbs. METHODS: Seven patients, including five with arteriosclerosis obliterans, one with Buerger's disease and one with progressive systemic sclerosis, underwent ten cell therapies. The first administration of rhEPO was performed two weeks before apheresis, and the second administration and blood donation were performed one week before apheresis to activate bone marrow. MNCs including CD34+ cells, isolated from peripheral blood by apheresis, were immediately injected intramuscularly into ischemic limbs. RESULTS: The number of peripheral blood-CD34 + cells had significantly increased from 1.32 ± 0.83/microL, before the rhEPO induction, to 1.86 ± 0.94/microL, before the apheresis. The number of transplanted MNCs ranged between 0.5 × 10(9) and 16.5 × 10(9), and that of CD34+ cells, between 0.1 × 10(6) and 12.7 × 10(6), accounting for 0.02%-0.1% of MNCs. There were no serious complications. Finger ulcers with Buerger's disease were significantly improved one month after the transplantations, but the same or other ulcer(s) appeared 2-6 months later. Three patients had an improvement in rest pain, and one patient extended maximum pain-free walking distance. CONCLUSIONS: Erythropoietin-induced autologous peripheral blood-MNC transplantation is a useful and safe alternative for ischemic limbs.

Functional restoration of endothelial cells of the cryopreserved heart valve.

PURPOSE: Although several approaches have been tried to improve the durability of cryopreserved valves, cellular restoration after thawing remains to be investigated. The aim of our study was to assess the functional restoration of endothelial cells of cryopreserved heart valves by in vitro culture for an alternative step to improving longevity. METHODS: Cryopreserved human umbilical vein endothelial cells (HUVECs) and porcine aortic cusps were cultivated for 14 days after thawing. Then the cellular activity of the enzymes cytosolic esterase and mitochondrial dehydrogenase was measured. The cellular viability of cryopreserved cusps was also assessed using confocal laser scanning microscopy. RESULTS: The number of viable HUVECs decreased markedly after cryopreservation and thawing but recovered to pre-cryopreservation level after 14 days of culture. In contrast, the enzyme activity of the cryopreserved porcine aortic cusps showed recovery at 7 days of in vitro tissue culture after thawing. Confocal laser scanning microscopy findings showed that the cellular cytosolic esterase activity of cryopreserved cusps deteriorated after thawing but displayed considerable recovery by day 14 of culture. CONCLUSION: The functional recovery of endothelial cells in cryopreserved heart valves seems to require tissue culture of at least 14 days. Ex vivo endothelial restoration of cryopreserved heart valves may add to heart valve durability.

Successful early resection of cardiac papillary fibroelastomas.

Two adult patients with previous transient cerebral ischemic attacks (TIAs) or chest oppression were referred for further investigation. A swaying pedicled tumor was detected in the left atrium of the former patient and in the left coronary cusp of the latter by echocardiography. The TIA, or angina-like attack, was anticipated to be caused by thromboembolism of the tumor. Both patients underwent tumor extirpation. The histological findings demonstrated that both tumors were benign papillary fibroelastoma limited to the endocardium/endothelium layer. In conclusion, early surgical resection of a cardiac papillary fibroelastoma should be performed.

Ezetimibe monotherapy ameliorates vascular function in patients with hypercholesterolemia through decreasing oxidative stress.

AIM: Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent. However, anti-atherogenic effects of ezetimibe have not been fully elucidated. Therefore, the objective in this study was to clarify the vascular protective effects of ezetimibe in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 20 patients with hypercholesterolemia (group E), and 20 age- and sex-matched patients with hypercholesterolemia were followed as controls (group C). Difference in metabolic profiles and cardiovascular surrogate markers before ezetimibe treatment and after 12 weeks of ezetimibe treatment were statistically evaluated. RESULTS: Ezetimibe treatment significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and malondialdehyde-modified low-density lipoprotein (MDA-LDL). In addition, the values of body mass index, body weight, waist circumference, plasma HbA1c and urinary albumin were significantly decreased in group E compared to those in group C. On the other hand, high-density lipoprotein cholesterol (HDL-C) and adiponectin levels were significantly increased in group E compared to those in group C. The values of brachial-ankle pulse wave velocity (ba-PWV), mean arterial blood pressure (m-ABP), and % of flow-mediated dilation (FMD) were significantly improved in group E. Furthermore, ultrasonic studies demonstrated amelioration of the vascular stiffness of common carotid arteries in group E but not in group C. These vascular protective effects of ezetimibe were statistically correlated with the decreased values of MDA-LDL and MDA-LDL-to-LDL-C ratio but not with those of LDL-C. CONCLUSION: Ezetimibe has a lipid lowering-independent vascular protective effect in patients with hypercholesterolemia through decreasing oxidative stress.

Assessment of systemic-pulmonary collateral arteries in children with cyanotic congenital heart disease using multidetector-row computed tomography: comparison with conventional angiography.

BACKGROUND: The present study aimed to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of systemic-pulmonary collateral (SPC) arteries in children with congenital heart disease associated with reduced pulmonary blood flow. METHODS: Forty-eight consecutive patients (mean age 9+/-5 months; range, 0-30 months) underwent MDCT angiography of the thorax with a 16-detector row scanner prior to cardiac catheterization and operation. Conventional angiographic findings were used as a gold standard for the detection of SPC vessels. Findings on CT angiograms, including CT scans, maximum intensity projections, and three-dimensional volume-rendered images, were used to evaluate depiction of SPC arteries. Quantification of measurements at the SPC artery diameter was evaluated independently on MDCT and conventional invasive angiography. RESULTS: Among the 48 patients, 115 SPC arteries were identified with conventional angiography, and 94 SPC arteries were identified with MDCT. In 89 (77%) vessels, concordant findings were observed with both modalities, with adequate depiction in 53 vessels and suboptimal depiction in 36 vessels. In 26 (23%) vessels, MDCT was unable to identify SPC arteries. Further, CT angiography resulted in the false-positive identification of vessels in 5 cases. There was an excellent correlation between MDCT- and conventional angiography-based measurement of SPC vessel diameter (R(2)=0.83), although a systematic overestimation was observed with MDCT (bias 0.19+/-0.74 mm). CONCLUSIONS: This study demonstrates that MDCT is a potentially useful tool, which may have implications for planning percutaneous interventions and surgical repair in the future.