Administration of an antibody against apoptosis inhibitor of macrophage prevents aortic aneurysm progression in mice.

Apoptosis inhibitor of macrophage (AIM) is known to induce apoptosis resistance in macrophages and to exacerbate chronic inflammation, leading to arteriosclerosis. The role of AIM in aortic aneurysm (AA) remains unknown. This study examined the effects of an anti-AIM antibody in preventing AA formation and progression. In apolipoprotein E-deficient mice, AA was induced by subcutaneous angiotensin II infusion. Mice were randomly divided into two groups: (i) AIM group; weekly anti-murine AIM monoclonal antibody injection (n = 10), and (ii) IgG group; anti-murine IgG antibody injection as control (n = 14). The AIM group, compared with the IgG group, exhibited reduced AA enlargement (aortic diameter at 4 weeks: 2.1 vs. 2.7 mm, respectively, p = 0.012); decreased loss of elastic lamellae construction; reduced expression levels of IL-6, TNF-α, and MCP-1; decreased numbers of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0%, respectively, p = 0.004; M1 macrophages: 24.5 vs. 55.7%, respectively, p = 0.017); and higher expression of caspase-3 in the aortic wall (22.8 vs. 10.5%, respectively, p = 0.019). Our results suggest that administration of an anti-AIM antibody mitigated AA progression by alleviating inflammation and promoting M1 macrophage apoptosis.

Thromboelastographic evaluation after cardiac surgery optimizes transfusion requirements in the intensive care unit: a single-center retrospective cohort study using an inverse probability weighting method.

OBJECTIVE: There are no reports from Japan showing the effects of using the thromboelastography algorithm on transfusion requirements after Intensive Care Unit (ICU) admission, and post-implementation knowledge regarding the thromboelastography algorithm under the Japanese healthcare system is insufficient. Therefore, this study aimed to clarify the effect of the TEG6s thromboelastography algorithm on transfusion requirements for patients in the ICU after cardiac surgery. METHODS: We retrospectively compared the requirements for blood transfusion up to 24 h after ICU admission using the thromboelastography algorithm (January 2021 to April 2022) (thromboelastography group; n = 201) and specialist consultation with surgeons and anesthesiologists (January 2018 to December 2020) (non-thromboelastography group; n = 494). RESULTS: There were no significant between-group differences in terms of age, height, weight, body mass index, operative procedure, duration of surgery or cardiopulmonary bypass, body temperature, or urine volume during surgical intervention. Moreover, there was no significant between-group difference in the amount of drainage at 24 h after ICU admission. However, crystalloid and urine volumes were significantly higher in the thromboelastography group than in the non-thromboelastography group. Additionally, fresh-frozen plasma (FFP) transfusion volumes were significantly lower in the thromboelastography group. However, there were no significant between-group differences in red blood cell count or platelet transfusion volume. After variable adjustment, the amount of FFP used from the operating room to 24 h after ICU admission was significantly reduced in the thromboelastography group. CONCLUSIONS: The thromboelastography algorithm optimized transfusion requirements at 24 h after admission to the ICU following cardiac surgery.

Development of novel waxy bone haemostatic agents composed of biodegradable polymers with osteogenic-enhancing peptides in rabbit models.

OBJECTIVES: The use of bone wax (BW) is controversial for sternal haemostasis because it increases the risk of wound infection and inhibits bone healing. We developed new waxy bone haemostatic agents made from biodegradable polymers containing peptides and evaluated them using rabbit models. METHODS: We designed 2 types of waxy bone haemostatic agents: peptide wax (PW) and non-peptide wax (NPW), which used poly(ε-caprolactone)-based biodegradable polymers with or without an osteogenesis-enhancing peptide, respectively. Rabbits were randomly divided into 4 groups based on treatment with BW, NPW, PW or no treatment. In a tibial defect model, the bleeding amount was measured and bone healing was evaluated by micro-computed tomography over 16 weeks. Bone healing in a median sternotomy model was assessed for 2 weeks using X-ray, micro-computed tomography, histological examination and flexural strength testing. RESULTS: The textures of PW and NPW (n = 12 each) were similar to that of BW and achieved a comparable degree of haemostasis. The crevice area of the sternal fracture line in the BW group was significantly larger than that in other groups (n = 10 each). The PW group demonstrated the strongest sternal flexural strength (n = 10), with complete tibial healing at 16 weeks. No groups exhibited wound infection, including osteomyelitis. CONCLUSIONS: Waxy biodegradable haemostatic agents showed satisfactory results in haemostasis and bone healing in rabbit models and may be an effective alternative to BW.

A review of current status of cell-based therapies for aortic aneurysms.

An aortic aneurysm (AA) is defined as focal aortic dilation that occurs mainly with older age and with chronic inflammation associated with atherosclerosis. The aneurysmal wall is a complex inflammatory environment characterized by endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) apoptosis, and the production of proinflammatory molecules and matrix metalloproteases (MMPs) secreted by infiltrated inflammatory cells such as macrophages, T and B cells, dendritic cells, neutrophils, mast cells, and natural killer cells. To date, a considerable number of studies have been conducted on stem cell research, and growing evidence indicates that inflammation and tissue repair can be controlled through the functions of stem/progenitor cells. This review summarizes current cell-based therapies for AA, involving mesenchymal stem cells, VSMCs, multilineage-differentiating stress-enduring cells, and anti-inflammatory M2 macrophages. These cells produce beneficial outcomes in AA treatment by modulating the inflammatory environment, including decreasing the activity of proinflammatory molecules and MMPs, increasing anti-inflammatory molecules, modulating VSMC phenotypes, and preserving elastin. This article also describes detailed studies on pathophysiological mechanisms and the current progress of clinical trials.

A rare case of delayed complete lead dislodgement after deep septal pacing: A hidden risk of the specific procedure.

Deep septal ventricular pacing is a recently developed physiological pacing modality with good efficacy; however, it has a potential risk of unusual complications. Here, we report a patient with pacing failure and spontaneous, complete lead dislodgement after >2 years of deep septal pacing, possibly caused by systemic bacterial infection and specific lead behavior in the septal myocardium. This case report may implicate a hidden risk of unusual complications in deep septal pacing.

Administration of anti-inflammatory M2 macrophages suppresses progression of angiotensin II-induced aortic aneurysm in mice.

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) plays a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE-/-) mouse model in which AA was induced by angiotensin II (ATII) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. Compared with a control group that was administered saline, the M2M group exhibited reduced AA expansion; decreased expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1); and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via regulating the M1M/M2M ratio. This study shows that M2M administration might be useful for the treatment of AA.

Impact of an improved driveline management for HeartMate II and HeartMate 3 left ventricular assist devices.

BACKGROUND: We evaluated the impact of a standardized driveline care strategy, including a subfascial-tunneling method and dressing protocol, on the incidence of driveline infection (DLI). METHODS: DLI data from all HeartMate II (HMII) and HeartMate 3 (HM3) patients (including exchange devices) were retrospectively collected between 2013 and 2021. The driveline subfascial-tunneling method was altered in three steps (A: right direct; B: left triple, C: right triple), and the shower protocol was changed in two steps (A: with/without cover, B: with cover). Disinfection was individually tailored after changing the shower protocol. Complications associated with morbidity and mortality were evaluated for each modification. RESULTS: During the study period, 80 devices were implanted (HMII, n = 54; HM3, n = 26). The 8-year incidence of DLI was 15% (n = 8) in HMII patients and 0% in HM3 patients (p = 0.039). DLI was not associated with hospital mortality. The modified dressing protocol and tunneling method was associated with a significantly better DLI incidence rate in comparison to the previous one: Protocol-A (n = 17), Protocol-B (n = 63), 35% vs 3% (p = 0.0009), Method-A (n = 13), Method-B (n = 42), Method-C (n = 25), 46% vs 5% vs 0% (p = 0.0001). The rete of freedom form DLI at 1, 2, and 3 years had also significant difference between groups: Protocol-A and Protocol-B, 80%, 54%, 54% vs 96%, 96%, 96%, respectively (p < 0.0001), Method-A, Method-B and Method-C, 76%, 44%, 44%, vs 94%, 94%, 94% vs 100%, 100%, respectively (p < 0.0001). CONCLUSIONS: A standardized triple driveline tunneling strategy and waterproof dressing protocol reduced driveline infection in HM3 patients to 0%.

Multiple giant coronary artery aneurysms with extended coronary ectasia emerging 12 years after previous coronary artery bypass grafting.

A 73-year-old man presented with multiple giant coronary artery aneurysms. Twelve years prior to the presentation, he had undergone coronary artery bypass grafting. At that time, he exhibited small aneurysms (16 mm diameter) in the right coronary artery and a single aneurysm (10 mm diameter) in the left circumflex artery. During follow-up, the aneurysms gradually increased in size (to 45 and 30 mm, respectively, at 12 years after surgery). We resected all of the aneurysms and performed coronary artery bypass grafting of the left circumflex artery through re-sternotomy.

Higher F-wave frequency associates with poor procedural success rate after Maze procedure.

OBJECTIVES: Persistent atrial fibrillation (AF) causes atrial remodeling, which causes myocardial fibrosis and micro-reentry. Fibrosis may reduce wave voltage and micro-reentry may enhance the dominant frequency (DF) of the F-wave. We investigated whether the DF predicts procedural success by the Maze procedure. METHODS: In 138 consecutive patients who underwent mitral valve surgery and a modified Cox-Maze III procedure for persistent AF in Nagoya University in 2002-2018, 96 (70%) were successfully cardioverted (group S); 42 had persistent or relapsed AF after surgery (group F). Patient data were compared between the groups. Cut-off values were determined by an ROC analysis and predictors of procedural success were evaluated. The DF was obtained from the F-wave of V1 by a high-speed Fourier analysis using the CEPAS software program. RESULTS: Group F showed a significantly larger LA diameter, better LVEF, lower F-wave voltage, higher DF, and longer duration of AF. The cut-off values were as follows: LA diameter, 56 mm; EF, 64.5%; F-wave voltage, 0.13 mV; DF, 7.3 Hz; and duration of AF, 44 months. Each factor showed statistical significance in a univariate analysis; DF lost significance in the multivariate analysis. The higher (DF ≥ 7.3 Hz) and lower voltage group (≤ 0.13 mV) showed the worst procedural success rate (36%), while the lower DF (< 7.3 Hz) and higher voltage group (> 0.13 mV) showed a good rate (86%). CONCLUSIONS: The DF of the F-wave is a useful predictor of procedural success after the Maze procedure in addition to the voltage of F-wave.

Bi-layered carboxymethyl cellulose-collagen vitrigel dual-surface adhesion-prevention membrane.

During wound regeneration, both cell adhesion and adhesion-inhibitory functions must be controlled in parallel. We developed a membrane with dual surfaces by merging the properties of carboxymethyl cellulose (CMC) and collagen using vitrification. A rigid membrane was formed by vitrification of a bi-layered CMC and collagen hydrogel without using cross-linking reagents, thus providing dual functions, strong cell adhesion-inhibition with the CMC layer, and cell adhesion with the collagen layer. We referred to this bi-layered CMC-collagen vitrigel membrane as "Bi-C-CVM" and optimized the process and materials. The introduction of the CMC layer conferred a "tough but stably wet" property to Bi-C-CVM. This enables Bi-C-CVM to cover wet tissue and make the membrane non-detachable while preventing tissue adhesion on the other side. The bi-layered vitrification procedure can expand the customizability of collagen vitrigel devices for wider medical applications.

Predictors of Failure of Mitral Valve Repair Using Artificial Chordae.

BACKGROUND: We investigated predictors of failure of mitral valve repair (MVr) using expanded polytetrafluoroethylene (ePTFE) and its durability in the long term in a single institution. METHODS: Four hundred twenty-one consecutive patients with primary mitral valve disease underwent MVr using artificial chordae (group A, n = 304) and suture repair (group S, n = 117) at our institution from January 2002 to April 2020. A comparison study was performed to examine the long-term outcomes, reoperation rate, and risk factors for reoperation. RESULTS: One hospital death and 5 late deaths occurred in group S, and 20 late deaths occurred in group A. The reoperation rates were similar: group A, n = 8 (2.6%); and group S, n = 6 (5%). The major cause of reoperation was ruptured ePTFE (CV-4, n = 1; CV-5, n = 6) in group A, and suture rupture in group S. Reoperation was performed after a median of 88 months for ruptured ePTFE, and 26 months for group S. The rate of ePTFE rupture was 1.8% with CV-5 and 0.2% with CV-4. Risk factors for reoperation included postoperative arrhythmia, urgent operation, no annular ring, ruptured ePTFE, and suture rupture. The rates of freedom from reoperation and actuarial mitral valve survival rates at 5, 10, and 15 years were 99%, 95%, and 93% and 96%, 91%, and 89%, respectively, in group A; and 96%, 91%, and 91% and 95%, 94%, and 94%, respectively, in group S. CONCLUSIONS: The long-term surgical outcomes of MVr using both techniques were feasible. Over the long term, the ePTFE rupture rate of CV-5 was higher than that of CV-4.

Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell-derived exosomes.

BACKGROUND: Several studies demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-exs) based on their anti-inflammatory properties. The objective was to determine the therapeutic effects of MSC-exs on aortic aneurysms (AAs) caused by atherosclerosis. RESEARCH DESIGN AND METHODS: Apolipoprotein E knockout mice with AAs induced by angiotensin II were injected with MSC-exs or saline as a control. The change in the diameter of the aorta was measured. The expression of AA-related proteins and the histology of the aortic wall were investigated at 1 week after treatment. MicroRNA and protein profiles of MSC-exs were examined. RESULTS: MSC-exs significantly attenuated AA progression (2.04 ± 0.20 mm in the saline group and 1.34 ± 0.13 mm in the MSC-ex group, P = 0.004). In the MSC-ex group, the expression of IL-1ß, TNF-α and MCP-1 decreased, and expression of IGF-1 and TIMP-2 increased. MSC-ex induced the M2 phenotype in macrophages and suppressed the destruction of the elastic lamellae in the aortic wall. MSC-exs contained high levels of 10 microRNAs that inhibit AA formation and 13 proteins that inhibit inflammation and promote extracellular matrix synthesis. CONCLUSIONS: MSC-ex might be a novel alternative therapeutic tool for treatment of existing AAs.

Sudden circulatory collapse caused by mechanical obstruction of the left main coronary trunk with infective endocarditis vegetation: a case report.

BACKGROUND: Acute coronary syndrome (ACS) caused by mechanical obstruction of the coronary artery with a vegetation is extremely rare but associated with high mortality. The optimal management strategy of this condition remains controversial because of its scarcity. We experienced a case of sudden circulatory collapse due to mechanical occlusion of the left main coronary trunk with a vegetation. CASE PRESENTATION: A 68-year-old woman with aortic and mitral valve infective endocarditis suffered sudden dyspnea followed by heart arrest while awaiting surgery. Despite treatment with adequate antibiotic therapy, she had had multiple embolic infarctions and ruptured infectious cerebral aneurysms. We conducted transcatheter arterial embolization of the aneurysm and postponed the cardiac surgery due to residual aneurysmal blood flow. She suffered sudden cardiac arrest, and extracorporeal membrane oxygenation was applied after cardiopulmonary resuscitation. An echocardiogram revealed diffuse severe hypokinesis, and emergency coronary angiography was performed under suspicion of ACS. It revealed obstruction of the left main coronary trunk by a vegetation. Emergent cardiac surgery was performed. A vegetation had occluded the left coronary orifice. Aortic and mitral valve replacement with coronary artery bypass to the left antero-descending branch was performed. Regarding her cardiac function, she still required extracorporeal membrane oxygenation after surgery. She passed away 19 days after surgery due to multiple organ failure. CONCLUSIONS: ACS caused by mechanical obstruction of the coronary artery with a vegetation is rare but associated with high mortality. When circulatory collapse acutely occurs in patients with aortic valve infective endocarditis, we should suspect acute coronary artery obstruction. Urgent coronary angiography is mandatory to rescue the patient while preparing for emergency surgery.

Fabrication of Cationic Poly(vinyl alcohol) Films Cross-Linked Using Copolymers Containing Quaternary Ammonium Cations, Benzoxaborole, and Carboxy Groups.

Water-insoluble cationic poly(vinyl alcohol) (PVA) films were fabricated using a mixed aqueous solution of PVA and poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC)-co-methacrylic acid (MAAc)-co-5-methacrylamido-1,2-benzoxaborole (MAAmBO)) copolymer (3D). The surface of the PVA film is typically negatively charged, and simple fabrication methods for water-insoluble PVA films with cationic surface charges are required to expand their application fields. METAC, which has a permanent positive charge owing to the presence of a quaternary ammonium cation, was selected as the cationic unit. The MAAc and MAAmBO units were used as two types of cross-linking structures for the thermal cross-linking of the hydroxy and carboxy groups of the MAAc unit (covalent bonding) as well as the diol and benzoxaborole groups of the MAAmBO unit (dynamic covalent bonding). The films were thermally cross-linked at 135 °C for 4 h without the addition of materials. After immersion in surplus water at 80 °C for 3 h, the cross-linked PVA/3D films retained almost 100% of their weights. The ζ-potential of the water-insoluble PVA/3D film was 9.4 ± 0.8 mV. The PVA/3D film was strongly dyed using anionic acid red 1 (AR1) because of its positively charged surface. Interestingly, it could also be slightly dyed using cationic methylene blue (MB) and became transparent (original state) after immersion in water for 2 days. These results suggested that positive and negative charges coexisted in the PVA/3D film, and the surface properties were positively inclined. Moreover, the degree of hemolysis of the PVA/3D films was similar to that of the negative control, which showed high blood compatibility. To our knowledge, this is the first report on the fabrication of water-insoluble cationic PVA films using two types of cross-linking structures containing carboxy and benzoxaborole groups. The cross-linked PVA films were analyzed using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and contact angle (CA) and ζ-potential measurement, as well as by determining the mechanical properties, adsorption of charged molecules, and biocompatibility. These readily fabricated water-insoluble PVA films with positive charges can show potential applications in sensors, adsorption systems, and antimicrobial materials.

Long term efficacy and fate of a right ventricular outflow tract replacement using an elastomeric cardiac patch consisting of caprolactone and D,L-lactide copolymers.

For decades, researchers have investigated the ideal material for clinical use in the cardiovascular field. Several substitute materials are used clinically, but each has drawbacks. Recently we developed biodegradable and elastic poly(ε-caprolactone-co-D,L-lactide) (P(CL-DLLA)) copolymers by adjusting the CL/DLLA composition, and evaluated the long-term efficacy and outcomes of these copolymers when used for right ventricular outflow tract (RVOT) replacement. This P(CL-DLLA) material was processed into a circular patch and used to replace a surgical defect in the RVOT of adult rats. Control rats were implanted with expanded polytetrafluoroethylene (ePTFE). Histologic evaluation was performed at 8, 24, and 48 weeks post-surgery. All animals survived the surgery with no aneurysm formation or thrombus. In all periods, ePTFE demonstrated fibrous tissue. In contrast, at 8 weeks P(CL-DLLA) showed infiltration of macrophages and fibroblast-like cells into the remaining material. At 24 weeks, P(CL-DLLA) was absorbed completely, and muscle-like tissue was present with positive staining for α-sarcomeric actinin and cardiac troponin T (cTnT). At 48 weeks, the cTnT-positive area had increased. The biodegradable and elastic P(CL-DLLA) induced cardiac regeneration throughout the 48-week study period. Future application of this material as a cardiovascular scaffold seems promising. STATEMENT OF SIGNIFICANCE: Biomaterials for reconstruction of tissue deficiencies in cardiovascular surgery require having suitable mechanical properties for cardiac tissue and biodegradation resulting in native tissue growth. Several biodegradable polymers such as poly-ε-caprolactone (PCL) and polylactic acid (PLA) have excellent biocompatibility and already been widely used clinically. In general, PCL and PLA are quite mechanically rigid. Meanwhile, significant elasticity is required in the high-pressure environment of the heart while the material is being replaced by new tissue. The present study provides a novel four-armed crosslinked poly(ε-caprolactone-co-D,L-lactide) (i.e., P(CL-DLLA)) material for cardiac patch, which was demonstrated properties including tissue-compatible, super-elastic nature, that made it suitable for long-term, in vivo RVOT repair. This super-elastic biomaterial could be useful for reconstruction of various muscular tissues deficiencies.

Hypofibrinogenemia can be estimated by the predictive formula in aortic surgery.

OBJECTIVE: Aortic surgery often causes massive bleeding due to hypofibrinogenemia. Predicting hypofibrinogenemia is useful for developing a hemostasis strategy, including preparing for blood transfusion. We made a formula for predicting the serum fibrinogen level (SFL) at the termination of cardiopulmonary bypass (CPB) in aortic surgery and examined its validity. METHODS: We performed a retrospective observational study that consisted of 267 patients (group A) who underwent aortic surgery from July 2013 to December 2016 and made a formula for predicting the SFL at the termination of CPB in group A by a multiple linear regression analysis. The validity of this formula was then examined in another 60 patients (group B) who underwent aortic surgery from January 2017 to December 2017. RESULTS: We developed the following predictive formula: SFL at the termination of CPB (mg/dL) = 14.7 + 0.44 × preoperative SFL (mg/dL) + (- 0.14) × CPB time (min) + 0.64 × preoperative body weight (kg) + (- 17.3) × lateral thoracotomy (Yes/No, Yes: 1, No: 0). In group B, the predictive formula proved to be statistically valid in group B (R2 = 0.531, p < 0.001). CONCLUSION: The SFL at the termination of CPB in aortic surgery can be predicted by the preoperative SFL, body weight, CPB time and surgical approach. The predictive formula is useful for developing a hemostasis strategy, including preparing for blood transfusion.

Is Hybrid Repair for an Entire Shaggy Aorta Feasible?

OBJECTIVE: This paper reviewed clinical experiences to evaluate the feasibility of a surgical strategy for an entire shaggy aorta. METHODS: Fifty-two (52) surgeries (47 men, average age 72±7 years) were performed for an entire shaggy aorta at the current institution from 2002-2017. Open surgery was performed in 30 cases, including total arch replacement in 12, extended aortic arch replacement via L-shaped thoracotomy in 10 and median sternotomy combined with left thoracotomy in two, and thoracoabdominal aortic replacement in six. Hybrid procedures were performed in 22 cases: type I hybrid arch repair in six, type II hybrid arch repair in seven and type III hybrid arch repair in nine. RESULTS: Hospital mortality was significantly higher with a hybrid repair: surgical, one case (3%); hybrid, six cases (27%), (p=0.0125). Stroke occurred at relatively high rates in both groups: surgical, seven cases (23%); hybrid, six cases (27%) (p=0.75). Spinal cord injury was significantly higher in hybrid repair: surgical, one case (3%); hybrid, seven cases (32%), (p=0.004). Open surgery revealed a better long-term survival rate than the hybrid procedure at 5 and 10 years: surgical, 82%, 65.7%; hybrid, 53%, 35.1%, respectively (p=0.0452). The rate of freedom from aortic events was significantly better with open surgery than a hybrid procedure at 5 and 10 years: surgical, 96%, 85%; hybrid, 83%, 41.3%, respectively (p=0.0082). CONCLUSIONS: Surgery for an entire shaggy aorta was frequently associated with embolic complications such as stroke, paraplegia, renal failure, and bowel necrosis. However, open surgical repair may produce better early and late outcomes and freedom from aortic events compared with hybrid repair.

Therapeutic effect of allogeneic bone marrow-derived mesenchymal stromal cells on aortic aneurysms.

We previously reported the effectiveness of autologous mesenchymal stromal cells (MSCs) for the treatment of aortic aneurysm (AA), mediated mainly by these cells' anti-inflammatory properties. In this study, we investigate whether the therapeutic effects of allogeneic MSCs on AA are the same as those of autologous MSCs. To examine the immune response to allogeneic MSCs, C57BL/6 lymphocytes were co-cultured with BALB/c MSCs for 5 days in vitro. Apolipoprotein E-deficient C57BL/6 mice with AA induced by angiotensin II were randomly divided into three groups defined by the following intravenous injections: (i) 0.2 ml of saline (n = 10, group S) as a control, (ii) 1 × 106 autologous MSCs (isolated from C57BL/6, n = 10, group Au) and (iii) 1 × 106 allogeneic MSCs (isolated from BALB/c, n = 10, group Al). Two weeks after injection, aortic diameters were measured, along with enzymatic activities of MMP-2 and MMP-9 and cytokine concentrations in AAs. Neither allogenic (BALB/c) MSCs nor autologous (C57BL/6) MSCs accelerated the proliferation of lymphocytes obtained from C57BL/6. Compared with group S, groups Au and Al had significantly shorter aortic diameters (group S vs Au vs Al; 2.29 vs 1.40 vs 1.36 mm, respectively, p < 0.01), reduced MMP-2 and MMP-9 activities, downregulated IL-6 and MCP-1 and upregulated expression of IGF-1 and TIMP-2. There were no differences in these results between groups Au and Al. Thus, our study suggests that treatment with allogeneic MSCs improves chronic inflammation and reduced aortic dilatation. These effects were equivalent to those of autologous MSCs in established mouse models of AA.

Surgery for Anomalous Papillary Muscle Directly Into the Anterior Mitral Leaflet.

BACKGROUND: The anomalous insertion of papillary muscle directly into the anterior mitral leaflet is a rare congenital anomaly concomitant with hypertrophic cardiomyopathy. We herein report our surgical technique, which is designed to relieve left ventricular obstruction and preserve the mitral valve and subvalvular apparatus. METHODS: Among 38 patients who underwent septal myectomy from 2007 to 2020, 4 had an anomalous mitral subvalvular apparatus with papillary muscle with direct insertion into the anterior mitral leaflets. In all cases, mitral valve repair was accomplished with excision and reconstruction of all anomalous papillary muscles, concomitant with septal myectomy. In another 34 patients, 20 cases needed mitral valve repair with regard to systolic anterior motion by hypertrophic cardiomyopathy. The comparison study was conducted between the anomalous papillary muscle group (group A) and the others (group B). RESULTS: There was no early or late death in group A, and there were 3 early deaths and 2 late deaths in group B. The mean peak gradient in the left ventricle was significantly decreased in both groups. Mitral valve regurgitation grade was also significantly decreased from 3 to 0.5 without valve replacement in group A, and from 2 to 0.6 in group B. Six patients needed mitral valve replacement because of the thickness of anterior mitral leaflet in group B. CONCLUSIONS: Hypertrophic obstructive cardiomyopathy associated with the anomalous insertion of papillary muscle can be successfully treated without mitral valve replacement. Excision and reconstruction with the anomalous papillary muscle seems to be a feasible operation to reduce mitral regurgitation and relieve outflow tract obstruction.

Sutures on the Anterior Mitral Leaflet to Prevent Systolic Anterior Motion.

Mitral valve systolic anterior motion and associated regurgitation remain a challenging problem in mitral valve plasty. A simple procedure to correct intraoperative systolic anterior motion using sutures applied between the tip of the anterior leaflet and the posterior annulus is presented. This technique reduces the movement of the anterior leaflet toward the septum while maintaining sufficient valve orifice area.