Hideki Oshima

Novel Small-Caliber Vascular Grafts With Trimeric Peptide for Acceleration of Endothelialization

BACKGROUND Both rapid endothelialization and the prevention of intimal hyperplasia are essential to improve the patency of small-caliber vascular grafts (SCVGs). Using the peptide array based screening system, we identified the peptide CAG (cysteine-alanine-glycine), which has a high affinity for endothelial cells and a low adhesive property for smooth muscle cells (SMCs). In this article, we report an in vivo analysis of novel vascular grafts that were constructed with a biodegradable polymer (poly-ε-caprolactone [PCL]) containing CAG peptide. METHODS The novel SCVG, which measured 0.7 mm in diameter and 7 mm in length, was fabricated using the electrospinning technique. Carotid arterial replacement was performed on Sprague-Dawley rats using SCVGs with (group CAG) or without CAG (group C). Histologic and biochemical assessments were performed at 1, 2, and 6 weeks after implantation. RESULTS The ratio of endothelialization was significantly higher in group CAG compared with group C (CAG versus C, 64.4±20.0% versus 42.1±8.9% at 1 week; p=0.017; 98.2±2.3% versus 72.7±12.9% at 2 weeks; p=0.001; and 97.4±4.6% versus 76.7±5.4% at 6 weeks; p<0.001). Additionally, Western blot analysis showed that the level of endothelial nitric oxide synthase (eNOS) at 1 week in group CAG was significantly higher than that in group C (CAG versus C, 1.20±0.37 versus 0.34±0.16; p=0.013), and that α-smooth muscle actin (ASMA) at 6 weeks in group CAG was significantly lower than that in group C (CAG versus C, 0.89±0.06 versus 1.25±0.22; p=0.04). CONCLUSIONS The graft with CAG promoted rapid endothelialization and the potential for inhibition of intimal hyperplasia.

Outcome of Pericardiectomy for Constrictive Pericarditis in Japan: A Nationwide Outcome Study

BACKGROUND We evaluated the current results and the predictors of in-hospital complications for a pericardiectomy procedure for constrictive pericarditis in Japan. METHODS A total of 346 patients who underwent isolated pericardiectomy for constrictive pericarditis nationwide between 2008 and 2012 were identified from the Japan Adult Cardiovascular Surgery Database. RESULTS The patients were a mean age of 65.7 ± 11.7 years. The operative approach was through a median sternotomy in 90% of the patients. Cardiopulmonary bypass was used in 28.9%. The operative mortality rate was 10.0%, and the composite operative mortality or major morbidity (stroke, reoperation for bleeding, need for mechanical ventilation for more than 24 hours postoperatively due to respiratory failure, renal failure with newly required dialysis or mediastinitis) was 15.0%. Logistic regression analysis revealed that the predictive factors for composite operative mortality or major morbidity were preoperative chronic lung disease (odds ratio [OR], 4.75; p < 0.001), New York Heart Association functional class IV (OR, 3.85; p < 0.001), previous cardiac operation (OR, 2.68; p = .006), preoperative renal failure (OR, 2.62; p = .014), and cardiopulmonary bypass during the operation (OR, 2.46; p = .015). The frequency of using cardiopulmonary bypass was 2.9% in the patients treated through a left thoracotomy approach vs 31.8% in the patients treated through a median sternotomy approach (p < 0.0001). CONCLUSIONS Pericardiectomy is associated with high morbidity and mortality rates. Careful consideration should be given to these risk factors in the process of patient selection and perioperative management.

Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse

BackgroundMesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses. We previously reported that intra-abdominal implantation of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy attenuated angiotensin II (AngII)-induced aortic aneurysm (AA) growth in apolipoprotein E-deficient (apoE−/−) mice through anti-inflammation effects. However, cell delivery by laparotomy is invasive; we here demonstrated the effects of multiple intravenous administrations of BM-MSCs on AngII-induced AA formation.MethodsBM-MSCs were isolated from femurs and tibiae of male apoE−/− mice. Experimental AA was induced by AngII infusion for 28 days in apoE−/− mice. Mice received weekly intravenous administration of BM-MSCs (n=12) or saline (n=10). After 4 weeks, AA formation incidence, aortic diameter, macrophage accumulation, matrix metalloproteinase (MMP)’ activity, elastin content, and cytokines were evaluated.ResultsAngII induced AA formation in 100% of the mice in the saline group and 50% in the BM-MSCs treatment group (P < 0.05). A significant decrease of aortic diameter was observed in the BM-MSCs treatment group at ascending and infrarenal levels, which was associated with decreased macrophage infiltration and suppressed activities of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin content of aortic tissues. In addition, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 significantly decreased while insulin-like growth factor-1 and tissue inhibitor of metalloproteinases-2 increased in the aortic tissues of BM-MSCs treatment group.ConclusionsMultiple intravenous administrations of BM-MSCs attenuated the development of AngII-induced AA in apoE−/− mice and may become a promising alternative therapeutic strategy for AA progression.

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.

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.

Therapeutic potential of bone marrow-derived mesenchymal stem cells in formed aortic aneurysms of a mouse model

OBJECTIVES An aortic aneurysm (AA) is caused by atherosclerosis with chronic inflammation. Mesenchymal stem cells (MSCs) have potential anti-inflammatory properties. In this study, we examined whether an already-formed AA can be treated by intravenous injection of bone marrow-derived (BM)-MSCs in a mouse model. METHODS AA was induced in apolipoprotein E-deficient mice by angiotensin II-infusion for 28 days through sub-cutaneous osmotic mini-pumps. After that, 1 × 10(6) BM-MSCs (in 0.2 ml saline) or 0.2 ml saline as a control was injected via the tail vein. Mice were sacrificed at 2 (saline group n = 10, BM-MSC group n = 10), 4 (saline group n = 6, BM-MSC group n = 7) or 8 weeks (saline group n = 5, BM-MSC group n = 6) after injection. The aortic tissues of each group were dissected. Aortic diameter, elastin content, matrix metalloproteinase (MMP)-2 and -9 enzymatic activity and cytokine concentrations were measured, as was macrophage infiltration, which was also evaluated histologically. RESULTS The incidence of AA in the BM-MSC group was reduced at 2 weeks (BM-MSC 40% vs saline 100%, P < 0.05), and aortic diameter was reduced at 2 and 4 weeks (2 weeks: 1.40 vs 2.29 mm, P < 0.001; 4 weeks: 1.73 vs 2.32 mm, P < 0.05). The enzymatic activities of MMP-2 and -9 were reduced in the BM-MSC group at 2 weeks (active-MMP-2: 0.28 vs 0.45 unit/ml, P < 0.05; active-MMP-9: 0.16 vs 0.34 unit/ml, P < 0.05). Inflammatory cytokines were down-regulated in the BM-MSC group (interleukin-6: 2 weeks: 1475.6 vs 3399.5 pg/ml, P < 0.05; 4 weeks: 2184.7 vs 3712.8 pg/ml, P < 0.05 and monocyte chemotactic protein-1: 2 weeks: 208.0 vs 352.7 pg/ml, P < 0.05) and insulin-like growth factor (IGF)-1 and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated in the BM-MSC group at 2 weeks (IGF-1: 4.7 vs 2.0 ng/ml, P < 0.05; TIMP-2: 9.5 vs 4.0 ng/ml, P < 0.001). BM-MSC injection inhibited infiltration of M1 macrophages and preserved the construction of elastin. CONCLUSIONS Our results suggest that BM-MSCs might be an effective treatment for AA. Further investigation is necessary to optimize the injected dosage and the frequency of BM-MSCs to prevent a transient effect.

Primary aortic intimal sarcoma

Aortic intimal angiosarcoma is extremely rare, and the prognosis of patients with a tumor is unfavorable even if they have undergone surgery. We treated a patient with primary intimal angiosarcoma of the aortic arch who underwent an operation. The tumor originated from the inner wall of the aortic arch on the lesser curve. In order to remove the tumor completely, the entire aortic arch from the ascending to the middle of descending aorta was resected through an L-shape skin incision. On histologic examination, an undifferentiated intimal sarcoma was diagnosed. It grew into the aortic lumen while spreading along the aortic intima, focally infiltrating the media. The postoperative course was uneventful. Postoperative CT performed at 6, 12 and 18 months after surgery showed no local recurrence or metastasis. According to some reports endoarterectomy has been performed to treat this type of tumor, since the malignant cells are thought to be limited to the luminal surface. However, we favor aortic resections and graft interpositions rather than an endoarterectomy because the tumor could have invaded the media.

A bioresorbable osteosynthesis device can induce an earlier sternal fusion after median sternotomy

OBJECTIVES We examined the impact of the bioresorbable osteosynthesis sternal pin (Super Fixsorb 30) on sternal healing after median sternotomy. METHODS Sixty-three patients who underwent aortic surgery through median sternotomy between January 2006 and March 2009 were analysed. Sternal pins were utilized in 36 patients in addition to the standard closure of the sternum with Ethibond sutures (Group A), and 27 patients received no pins with the standard Ethibond sternal closure (Group B). The occurrence of transverse sternal dehiscence, anterior-posterior displacement and complete fusion of the sternum were evaluated by a computed tomography scan. The cross-sectional cortical bone density area (CBDA) of the sternum was examined to evaluate the osteoconductivity of the sternal pin over a 12-month period. RESULTS There was no sternal displacement (0%) observed in Group A at discharge. Meanwhile, five displacements (18.5%) were observed in Group B (P = 0.007). The complete sternal fusion rates at 12 months postoperatively were 100% in Group A, and 21.6% in Group B (P < 0.001). A significant increase in the CBDA was observed in Group A (P < 0.001; between CBDA at discharge and 12 months postoperatively). CONCLUSIONS The Super Fixsorb 30 sternal pin reduced an anterior-posterior sternal displacement and facilitated an earlier sternal fusion. The pin may have the potential to promote osteogenesis.

Predictors of early graft failure after coronary artery bypass grafting for chronic total occlusion

OBJECTIVES Little is known regarding the transit-time flow measurement (TTFM) variables in grafts anastomosed to chronically totally occluded vessels (CTOs). We aimed to establish the TTFM cut-off values for detecting graft failure in bypass grafts anastomosed to chronically totally occluded arteries and clarify the relationship between early graft failure and the grade of collateral circulation/regional wall motion of the CTO territory. METHODS Among 491 patients who underwent isolated coronary artery bypass grafting (CABG) from 2009 to 2015, 196 cases with CTOs underwent postoperative coronary angiography within 1 month after CABG. Two hundred and forty-one CTOs in all patients were examined. Thirty-two CTOs (13%) were not bypassed and 214 conduits were anastomosed to CTOs and underwent intraoperative TTFM. Arterial conduits and saphenous vein grafts (SVGs) were used in 102 and 112 cases, respectively. Among the arterial conduit procedures that were performed, 78 involved the left internal thoracic artery (LITA), 10 involved the right internal thoracic artery (RITA) and 14 involved the right gastroepiploic artery (rGEA). Any graft showing Fitzgibbon type B or O lesions on angiography was considered to be a failing graft. RESULTS The insufficiency rates for LITA, RITA, rGEA and SVG procedures were 5.1, 10, 14.3 and 7.1%, respectively. The TTFM variables recorded in failing grafts had a significantly lower mean flow (Qmean) and higher pulsatility index (PI) compared with patent grafts. Furthermore, akinetic or dyskinetic wall motion in the territory of bypassed CTOs was observed at a significantly higher rate in failing grafts. A multivariable regression analysis and receiver operating characteristic analysis revealed good predictors of early graft failure as follows: a Qmean value of < 11.5 ml/min for arterial conduits, a PI value of >5.85 and akinetic/dyskinetic wall motion in the CTO territory for SVGs. The Rentrop collateral grade was not associated with early graft failure. CONCLUSIONS The Qmean value and PI value by the TTFM are useful to detect early graft failure in conduits anastomosed to CTOs. The collateral grade is not associated with graft failure; however, bypass grafting to CTOs with akinetic/dyskinetic wall motion should be carefully considered.

The treatment of infectious aneurysms in the thoracic aorta; our experience in treating five consecutive patients.

The surgical strategy for infected thoracic aortic aneurysms (ITAA) remains controversial. Effective antibiotic therapy is mandatory and surgical intervention is indicated only to prevent an aneurysmal rupture. In-situ reconstruction through an aseptic route is ideal; however, urgent surgery is often required in the uncontrolled infectious phase. Five patients were recently treated surgically for ITAA. They were all males with a mean age of 61.2 (range: 58-66) years. Two patients were operated on urgently in the active infectious phase due to impending aneurysmal rupture. A total arch reconstruction with an extra-anatomical bypass between the ascending aorta and both femoral arteries in one and an extended aortic arch resection with an in-situ graft reconstruction were performed in the other. The other three patients underwent in-situ graft reconstructions in the controlled infectious phase. Four patients had multiple aneurysms, including nine saccular or nodular aneurysms. Short-interval computed tomography (CT) re-examinations revealed a rapid enlargement of the aneurysms and confirmed the diagnosis. All patients successfully survived and are doing well without any evidence of a recurrent aortic infection. The surgical strategy for ITAA should be determined on a case-by-case basis under a careful follow-up with short-interval CT re-examinations.