Masato Mutsuga

Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering

Background: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. Methods: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. Results: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (α-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. Conclusion: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering.

Hybrid versus open repair of aortic arch aneurysms: comparison of postoperative and mid-term outcomes with a propensity score-matching analysis

OBJECTIVES Operative strategies for repairing aortic arch aneurysms should be re-evaluated following recent technical advances. METHODS Of 364 patients who underwent aortic arch repair between 2002 and 2014, 58 were high-risk subjects who received isolated hybrid arch repair (HAR) via median sternotomy (type I n = 32, type II n = 1 and type III n = 25). During this period, excluding patients with type A dissection or extensive aneurysms, 124 patients received isolated open arch repair via median sternotomy. The patients in the HAR and open arch repair groups were compared. A propensity score-matching analysis was applied to adjust for baseline risk factors. RESULTS The patients in the HAR group were older (77 years ± 6 vs 69 ± 9, P < 0.0001), exhibited a greater rate of malignancy (21 vs 4.8%, P = 0.0022) and had higher logistic EuroSCORE values (31 ± 18 vs 20 ± 15, P < 0.0001) than those in the open arch repair group. Following propensity score matching creating 38 matched pairs, the differences in preoperative risk diminished. Operative complications, including the mortality rate (2.6 vs 0%), were similar between the groups. Apart from the lower rates of cardiopulmonary bypass (CPB) and circulatory arrest, there was no apparent superiority of HAR with respect to patient recovery. The mean follow-up duration was 52.5 months, during which the rate of freedom from aortic events in the HAR and open arch repair groups was 79 and 99% at 24 months, respectively (P < 0.0001). CONCLUSIONS HAR achieves equivalent short-term results to standard open arch repair, with a decreased need for CPB. However, considering the inferior mid-term outcomes of this procedure, its indications should be limited to high-risk patients.

A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber

OBJECTIVE We developed a novel sustained drug-eluting device using tacrolimus-eluting biodegradable nanofiber to prevent anastomotic stricture and evaluated the effects in a rat abdominal aortic anastomosis model. METHODS In vitro and in vivo tacrolimus release tests for tacrolimus-eluting biodegradable nanofiber were performed to confirm its sustained release. To verify the prevention of anastomotic stricture, tacrolimus-eluting biodegradable nanofiber was placed around the end-to-end anastomosis of abdominal aorta in rats. Five rats were allocated to the following 5 groups: (1) control without tacrolimus-eluting biodegradable nanofiber, (2) 5 mg of nanofiber only (0 wt% of tacrolimus), (3) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.04 wt% of tacrolimus, (4) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.1 wt% of tacrolimus, and (5) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 1.0 wt% of tacrolimus. Morphometric and histologic analyses including immunohistochemistry were performed in each of the groups 2 weeks after the operation. RESULTS The tacrolimus-eluting biodegradable nanofiber gradually released tacrolimus for at least 1 month in vitro and in vivo. The ratio of intimal area was significantly reduced in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group compared with the other groups (0.26, 0.24, 0.25, 0.21, and 0.08 in control, 0 wt%, 0.04 wt%, 0.1 wt%, and 1.0 wt%, respectively, P < .05). The cells, which constitute intimal hyperplasia, were positive for smooth muscle actin and SMemb, and factor VIII revealed that endothelial cells covered the surface of the aortic lumen even in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group in immunohistochemistry. CONCLUSION Tacrolimus-eluting biodegradable nanofiber reduced neointimal hyperplasia and preserved endothelialization. This device may be useful in the prevention of anastomotic stricture.

Pseudoaneurysm from the mitral-aortic intervalvular fibrosa following endocarditis

A rare case of a pseudoaneurysm from the mitral-aortic intervalvular fibrosa following bacterial endocarditis in a 17-year-old male is presented. Destructive infection secondarily involved the mitral-aortic intervalvular fibrosa. Perforation of this portion resulted in the formation of the pseudoaneurysm situated at the base of the left ventricle between the aorta and the left atrium. With echocardiography, computed topography, angiography, and magnetic resonance imaging (MRI), a pseudoaneurysm was diagnosed. MRI especially revealed detailed information and the extension of pseudoaneurysm. Our patient underwent resection of the pseudoaneurysm, reconstruction of left ventricular outflow with glutaraldehyde-preserved bovine pericardium, and replacement of the aortic valve. His postoperative course was uneventful. No recurrence of endocarditis was detected in the following year.

Spinal cord protection during a thoracoabdominal aortic repair for a chronic type B aortic dissection using the aortic tailoring strategy

This study evaluated the clinical advantage of a novel technique to reconstruct a true lumen with aortic wall tailoring for aortic repair (aortic tailoring) or the reimplantation of intercostal arteries (vascular tube) in a chronic type B aortic dissection. Thirty-three consecutive extended thoracoabdominal aortic repairs have been performed for chronic type B dissection since 2000. The novel strategy was applied in 17 cases since 2004 including eight cases of aortic repair (group A) and nine cases of a vascular tube (group B). The other 16 cases were graft interposition in five and no reimplantation in 11 for group C. There were no surgical deaths in either group A or B, and only one late death in group C. No patients sustained transient or permanent paraplegia in group A and B, while three cases of paraplegia occurred in group C (18.8%). All of the intercostal arteries were well preserved in group A and an average of 9.8 intercostal arteries for nine patients were reimplantated in group B. The present technique can optimally preserve the intercostal arteries maximally and showed an excellent surgical mortality and morbidity, especially with regard to the protection of the spinal cord.

Development of novel drug-eluting biodegradable nano-fiber for prevention of postoperative pulmonary venous obstruction

Pulmonary venous obstruction (PVO) after correction of total anomalous pulmonary venous connection (TAPVC) frequently occurs due to intimal-hyperplasia and the required re-operation. We have developed a novel sustained-release drug delivery system, using Tacrolimus-eluting biodegradable nano-fiber (TEBN). It consists of nano-scale fiber composed of biodegradable polymer and Tacrolimus. This study evaluated the effects of TEBN for prevention of venous anastomotic stricture in a rat model to apply to PVO operation. Tacrolimus was incorporated into poly (L-lactide-co-glycolide). The venous stricture model was made by rat inferior vena cava anastomosis. The IVC anastomosis was covered with TEBN with 1.0 wt% Tacrolimus (n=12) or without TEBN as a control (n=12), and evaluated histologically at 1, 2, and 4 weeks after operation. The ratio of intimal area was significantly reduced in the TEBN group compared with the control group (ratio; 1 week: 0.43+/-0.26 vs. 0.07+/-0.04, P=0.04, 2 weeks: 0.39+/-0.19 vs. 0.05+/-0.02, P=0.01, 4 weeks: 0.31+/-0.15 vs. 0.09+/-0.04, P=0.03, control vs. TEBN, respectively). Histological findings showed endothelialization along the inner surface of the vein even in TEBN. The TEBN reduced intimal hyperplasia and preserved endothelialization even in a venous stricture. These results suggested that this strategy might be useful for prevention of recurrent PVO after TAPVC correction.

Extended total arch replacement via the L-incision approach: single-stage repair for extensive aneurysms of the aortic arch

OBJECTIVES Total arch replacement via the L-incision approach (a combination of left anterior thoracotomy and upper median sternotomy) can be used to achieve more extensive replacement. METHODS In the period between 2002 and 2014, 279 total arch replacement procedures were performed. After excluding cases of acute aortic dissection and cases involving concomitant, hybrid or frozen elephant trunk procedures, patients who underwent isolated total arch replacement via an L-incision (n = 29) and via median sternotomy (n = 143) were identified and the data pertaining to their cases were analysed. RESULTS Operative mortality was higher in the L-incision group than in the median sternotomy group (6.9 vs 2.1%); however, the difference was not statistically significant. The L-incision group displayed a higher rate of respiratory complications, including pneumonia (28 vs 7.0%, P = 0.0034), the need for tracheostomy (17 vs 2.1%, P = 0.0038) and pulmonary haemorrhage (6.9 vs 0%, P = 0.028). The rate of paraplegia was similar between the groups (0 vs 1.4%, P = 1.00), despite the wider range replaced via the L-incision approach (7.3 ± 1.5 vs 4.7 ± 0.8 anatomical zones, P < 0.001). The rates of other complications and functional recovery were similar. The long-term survival (73 vs 84% at 5 years) and aortic event-free rates (94 vs 96% at 5 years) were similar in both groups. CONCLUSIONS A combination of left anterior thoracotomy and upper median sternotomy can be applied to the single-stage repair of extended aneurysms with acceptable results in appropriately selected patients.

Strategy of Cardiovascular Surgery for Patients With Dementia as Evaluated by Mini-Mental State Examination

BACKGROUND The strategy for cardiovascular surgery in dementia patients is controversial, so we aimed to investigate whether preoperative dementia and its severity might affect the outcomes of cardiovascular surgery by evaluating with the Mini-Mental State Examination (MMSE). Methods and Results: The study group comprised 490 patients undergoing cardiovascular surgery. Their preoperative cognitive status was evaluated using the MMSE, and analysis was performed to compare the patients with MMSE score <24 (dementia group, n=51) or MMSE score 24-30 (non-dementia group, n=439). Furthermore, the effect of the severity of dementia was analyzed with a cut-off MMSE score of 19/20. Risk factors for surgical outcomes were explored using multivariate logistic regression analysis. Hospital mortality was 11.8% in the dementia group and 2.1% in the non-dementia group (P=0.002). Regarding the postoperative morbidities, the incidence of cerebrovascular disorder (P=0.001), pneumonia (P=0.039), delirium (P=0.004), and infection (P=0.006) was more frequent in dementia group. Among the patients with MMSE <20, hospital mortality was as high as 25%, and the rate of delirium was 58%. Multivariate logistic regression analysis revealed that MMSE score <24 (P=0.003), lower serum albumin (P=0.023) and aortic surgery (P=0.036) were independent risk factors for hospital death. CONCLUSIONS Preoperative dementia affects the outcomes of cardiovascular surgery with regard to hospital death and delirium. The surgical indication for patients with MMSE <20 might be difficult, but surgery with an appropriate strategy should be considered for patients with MMSE <24.

The changes of aortic diameter after aortic repair with aortic tailoring technique for chronic type B aortic dissection.

OBJECTIVES Aortic repair with aortic tailoring of the false lumen can preserve the true lumen and intercostal arteries naturally. It is a useful surgical strategy to prevent paraplegia. However, aortic remodelling of tailored segments in a late phase after surgery is another concern. This study investigates the destiny of aortic remodelling of tailored aorta. METHODS From June 2004 to April 2013, 21 consecutive patients underwent aortic tailoring operation for chronic type B aortic dissecting aneurysm. The mean age at operation was 60 ± 10 years (range, 43-77). The tailored aortic segments were followed by serial CT scanning with the mean follow-up period of 46 ± 32 months (range, 2-103). RESULTS There were no operative deaths but paraplegia in 1, stroke in 1 and reversible renal failure in 2 patients. There were two late deaths: one due to pneumonia and the other due to aneurysmal rupture of the abdominal aorta. Eighteen patients revealed a completely thrombosed false lumen and no expansion of the tailored aorta, with it remaining less than 40 mm in diameter during follow-up. However, 3 cases were associated with a patent false lumen and 2 cases revealed aortic events. The aortic event-free rate at 5 years was 95 ± 5.1% in all patients and 66 ± 27% in patients in the patent false lumen group. CONCLUSIONS Aortic tailoring is a useful surgical technique for chronic type B aortic dissection. Paraplegia and ischaemia of other visceral organs could less likely occur. Patients with a completely thrombosed false lumen revealed no aortic events; however, a patent false lumen was associated with a high risk of aortic events.

Hemorrhagic Pericardial Cyst Complicated with Constrictive Pericarditis: A Case Report

Pericardial cysts are rare abnormalities and are usually asymptomatic. Although several case reports on their diagnosis and treatment have been published, those on hemorrhagic pericardial cysts remain limited. We herein report the case of a 70-year-old man with a hemorrhagic pericardial cyst complicated with constrictive pericarditis 2 years after the initial diagnosis.