[Nonbacterial Thrombotic Endocarditis Caused by Antiphospholipid Antibody Syndrome:Report of a Case].

A 73-year-old woman with multiple episodes of cerebral infarction was diagnosed with nonbacterial thrombotic endocarditis( NBTE) and antiphospholipid antibody syndrome. Transesophageal echocardiography revealed highly mobile tumors both in the mitral and the aortic valve, and the patient underwent aortic and mitral valve replacement. Pathologically, tumor of the mitral valve was a thrombus, and that of the aortic valve was a papillary fibroelastoma. Early after surgery, a recurrent thrombus was found in the left atrium, but no organ embolization ensued, and the patient had no adverse event for six months thereafter. Surgery is indicated only in limited cases of NBTE, because postoperative anticoagulation therapy is hard to manage and clinical outcome is poor.

[Turner Syndrome Requiring Two Open Heart Surgeries:Report of a Case].

A 55-year-old woman was diagnosed with Turner syndrome following amenorrhea at age 20. Since then, hormone replacement therapy has been used in the obstetrics and gynecology department, but follow-up for cardiovascular disease has not been performed. At age 44, she was taken to our hospital for the first time because of acute aortic dissection and rupture, and urgently underwent total arch replacement. At age 55, she needed aortic valve and ascending aortic replacements for aortic regurgitation, ascending aortic aneurysm, and heart failure caused by the bicuspid aortic valve. Cardiovascular manifestation in Turner syndrome patients is common, and close follow-up using imaging studies may predict emergency diseases that critically affect patient's life. Medical professionals should inform patients and families of the value of follow-up.

Preservation of the infected thoracic aortic endograft with thoracoscopic drainage and continuous irrigation.

The gold standard for aortic endograft infection includes the excision of infected endograft, debridement, and reconstruction. However, these methods are not always the best option for patients with poor clinical status. We assessed the suitability of alternative methods for managing aortic endograft infection. The patient was a 72-year-old man whose previous abdominal surgeries provoked recurrent cholangitis. The patient had also undergone thoracic endovascular aortic repair (TEVAR). One month after the TEVAR, he was readmitted with high-grade fever and diagnosed with endograft infection. Due to his frail condition, we chose a less invasive and conservative strategy; thoracoscopic drainage with endograft preservation, followed by continuous irrigation. He recovered well, and has survived more than 2 years after the drainage procedure. In unstable patients or those with severe comorbidities who cannot tolerate endograft excision, thoracoscopic drainage with endograft preservation is less invasive, and can be a bridging or temporary solution.

Efficacy of Two-Dimensional Perfusion Angiography for Evaluations after Infrapopliteal Bypass Surgery for Critical Limb Ischemia.

Two-dimensional perfusion angiography (2DPA) is utilized in hybrid operating rooms. 2DPA produces color map images and functional parameters to provide more robust visual and quantitative evaluations than conventional angiography. Its efficacy was suggested in five patients following bypass surgery; unexpected results were obtained in one patient, leading to a decision to perform surgical re-anastomosis. Furthermore, we found that the general anesthesia eliminates body movements that tend to disrupt 2DPA results. 2DPA was more useful during surgical revascularization than conventional angiography and provided more detailed information.

Postoperative Dysphagia in Debranching Thoracic Endovascular Aortic Repair with Retroesophageal Carotid-Carotid Bypass.

A carotid-carotid bypass is commonly used in debranching thoracic endovascular aortic repair. When the bypass graft is placed in the retroesophageal position, the esophagus may be compressed by the graft from behind. Therefore, dysphagia may occur postoperatively as a serious complication. To avoid this issue, we recommend placing the bypass graft below the cricoid cartilage.

Uremic Toxins Affect the Imbalance of Redox State and Overexpression of Prolyl Hydroxylase 2 in Human Adipose Tissue-Derived Mesenchymal Stem Cells Involved in Wound Healing.

Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions. Consistent with the uremic-treated AT-MSCs, there was a definite imbalance of redox state and high expression of ROS in CKD-AT-MSCs isolated from early-stage CKD patients. In addition, a transplantation study clearly revealed that nAT-MSCs promoted the recruitment of inflammatory cells and recovery from ischemia in the mouse flap model, whereas CKD-AT-MSCs had defective functions and the wound healing process was delayed. Of note, the expression of prolyl hydroxylase domain 2 (PHD2) is selectively increased in CKD-AT-MSCs and its inhibition can restore the expression of HIF-1α and the wound healing function of CKD-AT-MSCs. These results indicate that more studies about the functions of MSCs from CKD patients are required before they can be applied in the clinical setting.

Endoleak detection after endovascular aneurysm repair using unenhanced MRI with flow suppression technique: Feasibility study in comparison with contrast-enhanced CT.

OBJECTIVES: To evaluate the feasibility of unenhanced motion-sensitized-driven equilibrium (MSDE)-prepared balanced turbo field echo (BTFE) sequences for detecting endoleaks after endovascular aneurysm repair (EVAR). METHODS: Forty-six patients treated with EVAR for aortic and/or iliac arterial aneurysms underwent contrast-enhanced CT and MSDE-prepared BTFE sequences with and without flow suppression. Two independent observers reviewed these sequences and their subtraction images and assigned confidence levels for detecting endoleaks. Relative contrast values were calculated by dividing signal intensities by those of paraspinal muscles. CT provided the reference standard. RESULTS: CT showed types I and II endoleaks in one and ten patients, respectively. Areas under receiver operating characteristic curves were 0.92 and 0.97 for observers 1 and 2, respectively. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of both observers were 91 (10/11), 91(32/35), 91 (42/46), 77 (10/13) and 97 % (32/33), respectively. Relative contrast values of endoleaks and flowing blood significantly decreased by flow suppression on MSDE-prepared BTFE images (P = 0.002 and P < 0.0001 respectively), and were significantly higher than those of the excluded aneurysms on subtraction images (P = 0.003 and P = 0.001, respectively). CONCLUSIONS: Unenhanced MSDE-prepared BTFE sequences are feasible for detecting endoleaks. KEY POINTS: • Flow suppression significantly reduces endoleak signals on MSDE-prepared BTFE images. • Subtraction images of MSDE-prepared BTFE sequences ± flow suppression demonstrate endoleaks. • MSDE-prepared BTFE sequences indicate high diagnostic values (>90 %) except PPV (77 %). • MSDE-prepared BTFE sequences need further refinement to reduce false positives. • Endoleaks can be detected without contrast injection using MSDE-prepared BTFE sequences.

Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT-MSCs.

Mesenchymal stem cells (MSCs) are defined as multipotent cells that can give rise to various kinds of differentiated mesenchymal cells, and are thus considered to be useful for clinical therapy. However, the big hurdles of MSC therapy are the inability of MSCs to reach the appropriate tissues or sites with high efficiency and engraftment after transplantation. In this study, we investigated how adipose tissue-derived MSCs (AT-MSCs) improve their homing ability after intravenous injection. We previously found that human endothelial progenitor cells with low aldehyde dehydrogenase activity (Alde-Low EPCs) are suitable for the treatment of ischemic tissues. In addition, we demonstrated that microvesicles (MVs) derived from Alde-Low EPCs possessed the ability to improve the homing ability of non-functional Alde-High EPCs, resulting in wound healing. We initially transfected MVs derived from Alde-Low EPCs (EMVs) to human AT-MSCs, which were originally unable to cure ischemic tissues by intravenous transplantation. Remarkably, AT-MSC transfected EMVs dramatically repaired the ischemic skin flap compared with AT-MSC derived-MV (MMVs) transfected AT-MSCs or control AT-MSCs. We then found that the expression of CXCR4, an important chemokine receptor for cell migration, was highly elevated in EMV-transfected AT-MSCs. Moreover, AT-MSCs transfected with EMVs, but not control AT-MSCs, migrated to wound sites after intravenous injection. Consequently, CD45(+) inflammatory cells were successfully recruited at the wound sites after the injection of EMV-transfected AT-MSCs. These results demonstrate that EMVs are a useful source to improve the homing ability and wound healing ability of MSCs at the wound sites.

Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo.

Microvesicles (MVs) derived from mesenchymal stem cells showed the ability to alter the cell phenotype and function. We previously demonstrated that type 2 diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) increase in cell aggregation and adhesion in vitro and impair wound healing in vivo. However, the characterization and function of MVs derived from human non-diabetic AT-MSCs (nAT-MSCs) remain unknown. In this study, we characterized nAT-MSC-derived MVs and their function after the transfection of dAT-MSCs with MVs using the scratch assay and a flap mouse model. We found that human nAT-MSC-derived MVs expressed MSC-surface markers and improved dAT-MSC functions by altering the expression of genes associated with cell migration, survival, inflammation, and angiogenesis as well as miR29c and miR150. Remarkably, the transfection of dAT-MSCs with nAT-MSC-derived MVs improved their migration ability in vitro and wound healing ability in a flap mouse model. These results demonstrate a promising opportunity to modify the function of dAT-MSCs for therapeutic stem cell application in diabetic patients.

Increased Expression of EGR-1 in Diabetic Human Adipose Tissue-Derived Mesenchymal Stem Cells Reduces Their Wound Healing Capacity.

The prevalence of type 2 diabetes mellitus (T2DM), which leads to diabetic complications, has been increasing worldwide. The possible applications of T2DM-derived stem cells in cell therapy are limited because their characteristics are still not fully understood. In this study, we characterized adipose tissue-derived mesenchymal stem cells (AT-MSCs) from diabetic patients (dAT-MSCs) and found that insulin receptor substrate-1 (IRS-1) was highly phosphorylated at serine 636/639 in dAT-MSCs. Moreover, we found that early growth response factor-1 (EGR-1) and its target genes of PTEN and GGPS1 were highly expressed in dAT-MSCs in comparison to healthy donor-derived AT-MSCs (nAT-MSCs). We observed impaired wound healing after the injection of dAT-MSCs in the ischemic flap mouse model. The expressions of EGR-1 and its target genes were diminished by small hairpin RNA-targeted EGR-1 (shEGR-1) and treatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) inhibitor (PD98059). Importantly, dAT-MSCs with shEGR-1 were able to restore the wound healing ability in the mouse model. Interestingly, under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) can bind to the EGR-1 promoter in dAT-MSCs, but not in nAT-MSCs. Together, these results demonstrate that the expression of EGR-1 was upregulated in dAT-MSCs through two pathways: the main regulatory pathway is the MAPK/ERK pathway, the other is mediated by HIF-1α through direct transcriptional activation at the promoter region of the EGR1 gene. Our study suggests that dAT-MSCs may contribute to microvascular damage and delay wound healing through the overexpression of EGR-1. Interrupting the expression of EGR-1 in dAT-MSCs may be a useful treatment for chronic wounds in diabetic patients.

Serum-free isolation and culture system to enhance the proliferation and bone regeneration of adipose tissue-derived mesenchymal stem cells.

Cell therapy using human mesenchymal stem cells (MSCs) is an attractive approach for many refractory diseases. Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are considered as a favorable tool due to its abundance in the body, easy proliferation, and high cytokine production potency. In order to avoid the risks associated with the use of fetal bovine serum (FBS) in culture that includes batch variations and contamination with pathogens, development of serum-free culture system has been initiated. We have formulated a completely serum-free culture medium (SFM) that could be used not only for the expansion of AT-MSCs but also for initial isolation. We demonstrate that the AT-MSCs isolated and cultured in serum-free medium (AT-MSCs/SFM) possess high proliferation capacity and differentiation potency to osteoblast, adipocyte, and chondrocyte lineages in vitro. In in vivo bone fraction model analysis, AT-MSCs/SFM showed higher bone repair potency and quality of the regenerated bone than the cells cultured in serum-containing medium (AT-MSCs/SCM). This was attributed to the (i) presence of translated cells in the bone, as evidenced by in vivo imaging of the illuminated translated cells and (ii) high level of expression and induction capacity of AT-MSCs/SFM for cytokine BMP2, CCL2, and CCL5. Taken together, we report a new serum-free culture system for AT-MSCs that is suitable for cell therapy.

Left Ventricular Perforation during Catheter Ablation in a Patient with Idiopathic Thrombocytopenic Purpura.

Preoperative gamma-globulin therapy was recently performed to prevent bleeding complications in a patient with concomitant idiopathic thrombocytopenic purpura undergoing cardiac surgery. Here we report the case of a 75-year-old male patient with idiopathic thrombocytopenic purpura, chronic aortic dissection, and funnel chest in whom a left ventricular perforation sustained during catheter ablation was repaired during emergent surgery. Despite preoperative gamma-globulin therapy not being performed, bleeding complications were prevented because platelets were preserved by avoidance of cardiopulmonary bypass use. Although the funnel chest made it difficult to secure the operative field, the deep pericardial sutures were effective in repairing the perforation without cardiopulmonary bypass.

A new technique of in vivo synchrotron radiation coronary microangiography in the rat.

BACKGROUND: Previously, in our laboratory, synchrotron radiation coronary microangiography (SRCA) using Langendorff-perfused rat hearts could visualize a coronary artery of 50 µm in diameter. However, in vivo rat SRCA poses the problem of compromised temporal resolution due to the rapid heart rate of rats. PURPOSE: To establish a simple method of in vivo rat SRCA with bradycardia induced by intravenous injection of adenosine triphosphate disodium hydrate (ATP). MATERIAL AND METHODS: SRCA was performed at the Photon Factory of the High Energy Accelerator Research Organization (Tsukuba, Japan). Eight male Wistar rats were anesthetized. A catheter for injecting the contrast material was inserted into the carotid artery. Temporary bradycardia was induced by an intravenous bolus injection of 5 mg of ATP, and SRCA was performed immediately thereafter. RESULTS: After ATP administration, the average heart rate decreased from 388 to 73 beats per minute. As a result, we could detect a coronary artery as small as 45 µm in diameter. CONCLUSION: Our SRCA system which has a high resolution of 9 µm per pixel could detect a coronary artery as small as 45 µm in diameter in the in vivo rat.

The role of CCL5 in the ability of adipose tissue-derived mesenchymal stem cells to support repair of ischemic regions.

Mesenchymal stem cells (MSC) are multipotent and possess high proliferative activity, and thus are thought to be a reliable cell source for cell therapies. Here, we isolated MSC from adult tissues--bone marrow (BM-MSC), dental tissue (DT-MSC), and adipose tissue (AT-MSC)--to compare how autotransplantation of these MSC effectively supports the repair of bone fracture and ischemic tissue. An analysis by in vitro differentiation assays showed no significant difference among these MSC. The degree of calcification at the joint region of bone fracture was higher in mice transplanted with AT-MSC than in mice transplanted with BM-MSC or DT-MSC. To compare the abilities of MSC, characterize how those MSC affect the repair of ischemic tissue, vascular occlusion was performed by ligation of the femoral artery and vein. Of note, the blood flow in the ischemic region rapidly increased in mice injected with AT-MSC, as contrasted with mice injected with BM- or DT-MSC. The number of CD45- and F4/80-positive cells at the femoral region was higher in AT-MSC recipients than in recipients of BM-MSC or DT-MSC. We evaluated the mRNA expression of angiogenic and migration factors in MSC and found the expression of CCL5 mRNA was higher in AT-MSC than in BM-MSC or DT-MSC. Transplantation of AT-MSC with impaired expression of CCL5 clearly showed a significant delay in the recovery of blood flow compared with the control. These findings have fundamental implications for the modulation of AT-MSC in the repair of vasculature and bone fracture.

Cardiac sympathetic activity assessed by heart rate variability indicates myocardial ischemia on cold exposure in diabetes.

Measurement of heart rate variability (HRV) is a non-invasive technique that can be used to investigate functioning of the autonomic nervous system, especially the balance between sympathetic and vagal activities. It is reported that dilatation of coronary microcirculation by augmentation of sympathetic nerve activity (SNA) caused by cold exposure was impaired in diabetes. The question of whether or not SNA in HRV could respond to coronary ischemia was evaluated by cold exposure in diabetic rats. It was found that diabetes with weight loss significantly increased SNA both in baseline and cold exposure, compared with control. A correspondence was also found with coronary ischemia. It can be concluded that measurement of HRV may provide useful information regarding the coronary risk of cold exposure in diabetes. (English translation of J Jpn Coll Angiol 2012; 52: 295-301).

Surgical removal of infected pacemaker leads without cardiopulmonary bypass after failed extraction using the Excimer Laser Sheath Extraction System.

With the growing number of cardiac pacemakers and internal cardioverter defibrillator implantations, problems with endocardial lead infection have been increasing. The newly developed Excimer Laser Sheath Lead Extraction System has been recognized as being highly useful for removing chronic infected leads. However, serious bleeding complications are a concern when this system is used. Here we report our experience with a 67-year-old man who was diagnosed with pacemaker endocarditis. Initially, lead removal was attempted using the Excimer Laser Sheath Extraction System, though this was abandoned because of severe adhesion of the leads and the junction of the supra vena cava (SVC) with the right atrium. Surgical removal of the leads was performed without using cardiopulmonary bypass and the leads were removed without any complications. During surgery, we found there was a silent perforation of the innominate vein brought about by the Excimer Laser Sheath System. Also, the junction of the SVC with the right atrium was thought to be an area potentially at high risk of perforation, because of a lack of surrounding tissue. It is our opinion that those who carry out procedures with the Excimer Laser Sheath System should understand the potential risk of perforation based on cardiac anatomy and should be prepared for lethal bleeding complications. Also, for emergent situations, we believe that close backup by a cardiovascular surgical team should be considered essential for performing the Excimer Laser Sheath Lead Extraction safely.

Surgical repair for rupture of a chronic traumatic thoracic aneurysm 14 years after injury: report of a case.

Traumatic thoracic aortic injury is a lethal condition. Because its mortality rate is extremely high in the acute phase, these patients rarely survive long enough for a chronic aneurysm to develop. We herein report a case of surgical repair for a ruptured chronic traumatic thoracic aneurysm. A 32-year-old man, who had been involved in a traffic accident 14 years earlier, was diagnosed with a rupture of a chronic traumatic thoracic aneurysm. Preoperative computed tomography showed that the ruptured aneurysm arose from the aortic isthmus and was accompanied by multiple daughter lesions. He underwent an aorta graft replacement with reconstruction of the left subclavian artery using both a median sternotomy and a left thoracotomy. The surgery was successful and the postoperative course was uneventful. Chronic traumatic thoracic aneurysm is usually a single lesion, and cases with daughter aneurysms have rarely been reported. We include a review of the previous literature and also discuss the etiology of this condition.

Prospective intraindividual comparison of unenhanced magnetic resonance imaging vs contrast-enhanced computed tomography for the planning of endovascular abdominal aortic aneurysm repair.

OBJECTIVE: This study clarified whether unenhanced magnetic resonance imaging (MRI) is an alternative to contrast-enhanced computed tomography (CT) for aortoiliac arterial measurement before endovascular abdominal aortic aneurysm repair (EVAR). METHODS: The institutional review board approved this prospective study. Twenty patients being considered for EVAR underwent MRI using a steady-state free-precession sequence in a 1.5-T system and contrast-enhanced CT within 4 weeks of each other. Two independent observers reviewed MRI and CT in random order using vessel analysis software and measured seven diameters, four lengths, and the angle of the aortoiliac arteries. The intermodality, interobserver, and intraobserver agreements were assessed for each measurement by intraclass correlation coefficients (ICCs) and the Altman-Bland method. Additionally, the observers independently recorded the number of bilateral renal arteries, decided EVAR suitability, and selected the main endograft on each modality. RESULTS: Intermodality ICCs for observers A and B showed ranges of 0.83 to 0.99 and 0.70 to 0.98; interobserver ICCs for MRI and CT showed ranges of 0.73 to 0.99 and 0.65 to 0.99; and intraobserver ICCs for MRI and CT showed ranges of 0.59 to 0.99 and 0.59 to 0.99. In intermodality, interobserver, and intraobserver comparisons, mean differences in diameters were included within the range -1 to +1 mm, excluding three of seven diameters on CT in interobserver comparison and one of seven on CT in intraobserver comparison. Mean differences in lengths were included within the range -5 to +5 mm, excluding one of four lengths in observer B in intermodality comparison and one of four on MRI and CT in interobserver comparison. All mean differences in angles were included within the range -5° to +5°. Both observers detected all 40 bilateral main renal arteries on MRI and CT. Of the 13 accessory renal arteries, observers A and B detected four (31%) and nine (69%), respectively, on MRI; in contrast, both observers detected 11 (85%) on CT. The observers independently determined that the same seven patients were suitable for EVAR on MRI and CT. Of the seven selected main endografts, seven and six diameters and five and six lengths agreed exactly between MRI and CT for observers A and B, respectively. CONCLUSIONS: Although contrast-enhanced CT remains the gold standard for preoperative EVAR planning, unenhanced MRI with steady-state free-precession sequence can be an alternative modality for patients with contraindications for CT, such as renal impairment, because the intermodality agreement for preoperative measurements is as good as interobserver and intraobserver agreement.

Reducing the dose of contrast medium in angiography by use of a highly sensitive receiver and synchrotron radiation system.

OBJECTIVE: Contrast medium causes side effects such as contrast-induced nephropathy, and the dose of contrast medium is a risk factor in their occurrence. To reduce doses of contrast medium, we developed an angiographic system with high definition and high sensitivity and reviewed its effectiveness. The system entails synchrotron radiation, which is characterized by high photon density and straightness of beam that together result in high resolution, and a high-gain avalanche rushing amorphous photoconductor receiver, which is 100 times more sensitive than conventional charge-coupled device cameras. MATERIALS AND METHODS: Diluted contrast medium was administered, and angiography of rat hindlimbs was performed with synchrotron radiation and the high-gain photoconductor receiver. The difference in gray-scale value between the background and contrast medium was calculated. Images were evaluated by counting of arteries. RESULTS: The difference in contrast at low levels was detected with the high-gain photoconductor receiver but not with the charge-coupled device camera. The photon density of synchrotron radiation with the high-gain photoconductor receiver was one-fifth that with the charge-coupled device camera. The high-gain photoconductor receiver had approximately 5 times the sensitivity of the charge-coupled device camera. CONCLUSION: Use of the synchrotron radiation and high-gain photoconductor receiver makes it possible to perform angiography with an extremely low concentration of contrast medium.

Identification of human placenta-derived mesenchymal stem cells involved in re-endothelialization.

Human placenta is an attractive source of mesenchymal stem cells (MSC) for regenerative medicine. The cell surface markers expressed on MSC have been proposed as useful tools for the isolation of MSC from other cell populations. However, the correlation between the expression of MSC markers and the ability to support tissue regeneration in vivo has not been well examined. Here, we established several MSC lines from human placenta and examined the expression of their cell surface markers and their ability to differentiate toward mesenchymal cell lineages. We found that the expression of CD349/frizzled-9, a receptor for Wnt ligands, was positive in placenta-derived MSC. So, we isolated CD349-negative and -positive fractions from an MSC line and examined how successfully cell engraftment repaired fractured bone and recovered blood flow in ischemic regions using mouse models. CD349-negative and -positive cells displayed a similar expression pattern of cell surface markers and facilitated the repair of fractured bone in transplantation experiments in mice. Interestingly, CD349-negative, but not CD349-positive cells, showed significant effects on recovering blood flow following vascular occlusion. We found that induction of PDGFß and bFGF mRNAs by hypoxia was greater in CD349-negative cells than in CD349-positive cells while the expression of VEGF was not significantly different in CD349-negative and CD349-positive cells. These findings suggest the possibility that CD349 could be utilized as a specialized marker for MSC isolation for re-endothelialization.