[Outcomes of Modified Bentall Procedure with French Cuff Technique].

BACKGROUND: We evaluated early and mid-term outcomes of modified Bentall procedure with French cuff technique for aortic root disease. METHODS: Between 2017 and 2024, 45 patients underwent modified Bentall procedure with French cuff technique. We excluded patients who had cardiopulmonary resuscitation. The mean age was 64.8± 14.0 years, and 35 patients were male( 77.8%). The mean predicted operative mortality rate according to JapanSCORE 2 was 11.2%. RESULTS: No patients had any trouble with bleeding from the aortic root. Hospital mortality was 2.2%, as one patient died due to a fungal infection. Twelve patients( 26.7%) experienced complications during hospitalization. The 3- and 5-year overall survival rates were 97.7% and 88.0%, respectively. Freedom from reoperation was 93.7% and 93.7% at 3 and 5 years, respectively. One patient underwent re-aortic valve replacement due to a stuck valve, and one underwent re-Bentall due to a seroma. There were no pseudoaneurysm formations of the aortic root and coronary ostia during the followed-up. CONCLUSIONS: The modified Bentall procedure with French cuff technique may be a useful technique with good outcomes.

Aortomitral angle affects cardiovascular events after mitral valve repair for atrial functional mitral regurgitation.

PURPOSE: This study aimed to elucidate the geometric parameters of the aortomitral (AM) complex affecting postoperative cardiovascular events (CVEs) in patients with atrial functional mitral regurgitation (MR). METHODS: From October 2008 to August 2018, we performed mitral and tricuspid valve repairs in 58 patients with atrial functional MR. We examined the determinants of CVEs using preoperative and postoperative echocardiographic data. Furthermore, we analyzed the effect of left atrial (LA) plication on AM geometries after surgery. The follow-up period ranged from 56 to 3283 days (median, 1073 days). RESULTS: All patients underwent mitral and tricuspid annuloplasty. Seventeen patients (29%) underwent additional LA plication. The AM angle was narrowed after surgery in patients with CVEs (115° ± 6.8° to 106° ± 4.2°, p = .00336), whereas it widened in patients without CVEs (115° ± 7.4° to 118° ± 8.4°, p = .0278). The postoperative AM angle was an independent predictor of postoperative CVEs (p = .000829). LA plication was not a predictor of CVEs; however, it was a predictor of the obtuse postoperative AM angle (p = .0071). CONCLUSIONS: Our results suggest that a narrow postoperative AM angle is an independent predictor of postoperative CVEs. Additional LA plication reduces the sharpening of the AM angle, which may prevent CVEs after mitral valve repair for atrial functional MR.

Acute exacerbation of idiopathic pulmonary fibrosis model by small amount of lipopolysaccharide in rats.

Idiopathic pulmonary fibrosis, a chronic and progressive lung disease with poor prognosis, presents with acute exacerbation. Pathophysiology and treatments for this acute exacerbation, and an appropriate animal model to perform such examinations, have not established yet. We presented a rat model for assessing acute exacerbation in cases of idiopathic pulmonary fibrosis. Wistar rats were intratracheally administered bleomycin (3 mg/kg) to induce pulmonary fibrosis. After 7 days, lipopolysaccharide (0, 0.05, or 0.15 mg/kg) was administered. In the bleomycin or lipopolysaccharide group, there were almost no change in the oxygen partial pressure, arterial blood gas (PaO2), plasma nitrite/nitrate, nitric oxide synthase, and lung nitrotyrosine levels. In the bleomycin (+)/lipopolysaccharide (+) groups, these three indicators deteriorated significantly. The plasma nitrite/nitrate and PaO2 levels were significantly correlated in the bleomycin (+) groups (r = 0.758). Although lung fibrosis was not different with or without lipopolysaccharide in the bleomycin (+) groups, macrophage infiltration was marked in the bleomycin (+)/lipopolysaccharide (+) group. There were many NOS2-positive macrophages, and the PaO2 levels decrease may be induced by the nitric oxide production of macrophages in the lung. This model may mimic the pathophysiological changes in cases of acute exacerbation during idiopathic pulmonary fibrosis in humans.

[Tips for Successful Robot-assisted Mitral Valve Repair].

Robot-assisted valve repair refers to an intervention added to conventional minimally invasive cardiac surgery( MICS), which is covered by national insurance since April 2018. However, currently, this procedure is performed only at a few hospitals, which is attributable to the need for specialized facilities, as well as surgeon-related criteria including high technical expertise. Notably, the learning curve to stabilize robotic surgery is longer than that for conventional MICS. Our hospital introduced robot-assisted valve repair in June 2018, and we have performed >120 surgeries to date. Our policy focuses on "no compromise in the quality of valve repair". The loop technique is routinely used for valve repair, and the experience gained from median sternotomy and MICS is directly applied to robotic procedures. Robot-assisted surgery enhances surgical field visualization and improves operability even in cases of complex valve repair. In this article, I will describe the procedural innovations, secure establishment of cardiopulmonary bypass, surgical outcomes, and the current challenges in robot-assisted valve repair to achieve safe and improved results.

[Robot-assisted Cardiac Surgery Council and Current Status and Future Prospect of Robotic Mitral Valve Surgery in Japan].

The Robot-assisted Cardiac Surgery Council (RACSC) was established in 2015, and consists of the members of three closely related surgical societies and associations. The RACSC conducts the review and approval of applicant surgeons and institutions. A registry system has also been established through the Japan Cardiovascular Surgery Database-National Clinical Database( JCVSD-NCD). For the last five years, including the time when robotic mitral valve surgery was first approved as a procedure covered by the Japanese social insurance system in 2018, a total of 1,161 patients were enrolled in the JCVSDNCD, with an increase of nearly 500 cases per year. These cases underwent operations in 25 approved hospitals. The mean patient age was 59±13 years( range:20-90 years), and the male to female patient ratio was 1.8 male dominant. The most common procedure was mitral valve reconstruction, and 79% of all patients underwent annuloplasty. The mean operative time was 238±100 min, the mean cardiopulmonary bypass (CPB) time was 158±69 min, and the mean aortic cross-clamp (AXC) time was 102±49 min. When these results were compared with those of the Cleveland Clinic, which treated more than 1,000 cases as an initial institutional experience, both CPB and AXC times were nearly the same. It is believed that 200 cases are needed to stabilize the CPB and AXC time. Currently in Japan, only 3 or 4 out of the 25 approved hospitals have performed more than 200 cases over the past 5 years. The 30-day hospital mortality and redo operation rate for persisting mitral regurgitation was 0.3% and 0.6%, respectively, almost equivalent to that of the Cleveland Clinic. We believe that the 5-year result for robotic mitral surgery in Japan is acceptable. It is of note, however, that the length of hospital stay was 10.8±7.6 days, much longer than that of patients at the Cleveland Clinic( 5.2±2.8 days), and the homologous blood transfusion rate was 40.3%, twofold higher than that of the Cleveland Clinic( 20.5%). Therefore, the full benefits of less invasive robotic mitral repair surgery have not yet been achieved. Further improvements in results are both essential and anticipated.

Segmental Atrophy of Explanted Livers in Biliary Atresia: Pathological Data From 63 Cases of Failed Portoenterostomy.

OBJECTIVES: Atrophy of the left lateral segment (LLS) is often encountered in liver transplantation (LT) for biliary atresia (BA). To clarify the meaning of the heterogeneous atrophy, we compared the pathological characteristics of the LLS with the right posterior segment (RPS) of BA livers obtained during LT. METHODS: Among the 116 patients with BA who underwent LT at our hospital between 2014 and 2018, 63 patients with persistent cholestasis after the Kasai portoenterostomy (KP) were selected. Three pathologists evaluated tissues from the LLS and RPS for 5 pathological parameters. Positive areas in whole-slide image observed as portal inflammation, fibrosis, cholestasis, and ductular reaction, were analyzed with automated image quantitation. Moreover, we examined the relationship between the pathological score and the Pediatric End-stage Liver Disease (PELD) score. RESULTS: The median age at LT was 7 months (range 4-26 months). Inflammation and fibrosis were significantly greater in the LLS than in the RPS (P < 0.001, for both); however, there were no differences in cholestasis, ductular reaction, and hepatocellular damage (P = 0.3, 0.3, and 0.82). The same results were obtained in automated image quantitation. Moreover, the sums of the 5 pathological scores in the LLS showed a significant positive correlation with the PELD score (P = 0.016, rs = 0.3). CONCLUSIONS: More severe inflammation and fibrosis without cholestasis were observed in the LLS. The segmental atrophy may not be associated with poor bile drainage, but with etiopathogenesis of BA. Moreover, the proper site for biopsy during KP could be the LLS.

The Optimal Definition of Sarcopenia for Predicting Postoperative Pneumonia after Esophagectomy in Patients with Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) is associated with malnutrition in the vast majority of patients, and this often leads to sarcopenia, which is characterised by loss of skeletal muscle mass (SMM). Although sarcopenia could be one of the risk factors for postoperative pneumonia (PP), the optimal definition of sarcopenia using skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) remains unknown for predicting PP after esophagectomy in patients with EC. Therefore, this study aimed to identify high-risk patients for PP after esophagectomy through evaluating SMI by BIA and set an appropriate cut-off value for this purpose. METHOD: A total of 73 patients with EC who underwent subtotal esophagectomy with lymph node dissection at Osaka City University Hospital between 2017 and 2019 were reviewed retrospectively. The association between PP and perioperative factors including SMI by BIA were analysed. When SMI was lower than the cut-off values proposed by two study groups (Asian Working Group for Sarcopenia (AWGS) and original European Working Group on Sarcopenia in Older People (EWGSOP)) or SMM was less than 90% of standard, the patient was diagnosed with sarcopenia. Receiver operating characteristic analysis was performed to set the appropriate cut-off value of SMI, and a new criterion (modified EWGSOP) was formulated by using the value. Clinicopathological factors and postoperative complications between sarcopenia and non-sarcopenia groups were compared, which were classified by four different criteria: (1) AWGS, (2) original EWGSOP, (3) < 90% standard and (4) modified EWGSOP criteria. RESULTS: Nine patients (12.3%) were with PP grade III or higher. Total SMI as well as body mass index (BMI), transthyretin and % vital capacity (%VC) were found to be significantly associated with PP (Clavien-Dindo grade ≥ III). BMI, total and appendicular SMI of sarcopenic patients were found to be lower than those of non-sarcopenic patients. Low serum albumin and %VC were significantly associated with sarcopenia defined by modified EWGSOP criteria. The rate of PP was significantly higher in sarcopenic patients when the original and modified EWGSOP criteria were used (p = 0.0079 and 0.0015, respectively). A multivariate analysis revealed that sarcopenic state by modified EWGSOP criteria was the significant independent predictive factor of PP [p = 0.0031, hazard ratio (HR) = 10.1; 95% confidential interval (CI): 2.12-76.9]. CONCLUSION: Preoperative sarcopenia by modified EWGSOP criteria could be the best indicator using BIA for predicting PP after esophagectomy in patients with EC.

Corynebacterium jeikeium-induced infective endocarditis and perivalvular abscess diagnosed by 16S ribosomal RNA sequence analysis: A case report.

INTRODUCTION: Corynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis. CASE REPORT: A 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE. CONCLUSION: 16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.

Loop technique for degenerative mitral regurgitation due to extended prolapse.

PURPOSE: Our study aims to examine the midterm outcomes of the loop technique for extended mitral valve (MV) prolapse patients. METHODS: From October 2008 to August 2020, we performed MV repairs in 407 patients with severe mitral regurgitation (MR). Follow-up ranged in duration from 287 to 2899 days (median, 872 days). The prolapse extensiveness (p-score) was determined based on the ratio of prolapsing segment's areas to whole area. We divided the whole MV into 10 segments (A1, A2 medial, A2 lateral, A3, P1, P2 medial, P2 lateral, P3, AC, and PC). Patients were categorized into three groups according to the p-score: simple (0.1-0.2), intermediate (0.3-0.4), and extensive (0.5-0.9). RESULTS: All patients underwent MV repair with the loop technique. The rates of freedom from significant (moderate to severe or severe) MR at 5 and 7 years after surgery were 91% and 91%, respectively. There were 252, 115, and 40 patients in simple group, intermediate group, and extensive group, respectively. The following were significantly increased in extended group: Barlow disease (23/40 patients, p < .001), the number of loops (p for trend < .0001), and the technique score (p for trend < .0001). The rates of freedom from significant MR at 7 years after surgery were 92% in simple group, 87% in intermediate group, and 94% in extended group, respectively (p = .995). Receiver-operating characteristic curves showed a postoperative mild MR with a sensitivity of 86% and a specificity of 68% for predicting significant MR recurrence. CONCLUSIONS: MV repair using the loop technique was useful even in groups with extended prolapse.

The Impact of Aorto-Mitral Angle on New-Onset Atrial Arrhythmia after Mitral Valve Repair in Patients with Mitral Regurgitation.

In this study, we hypothesized that post-operative aorto-mitral angle might be associated to the occurrence of post-operative atrial arrhythmia (AA), including atrial fibrillation and atrial tachycardia, after mitral valve repair in patients with mitral regurgitation (MR). Thus, this present study aims to determine the effects of post-operative aorto-mitral angle on new-onset AA after mitral valve repair with mitral annuloplasty for the treatment of MR.In total, 172 patients without any history of AA underwent mitral valve repair with mitral annuloplasty in our institution between 2008 and 2017. Patient information, including medical records and echocardiographic data, were retrospectively studied.As per our findings, AA occurred in 15 (8.7%) patients during the follow-up period (median, 35.7 months; range, 0.5-132 months). The patients with AA were noted to have a longer cardiopulmonary bypass time and a smaller aorto-mitral angle at post-operative TTE than the others (119 ± 6° versus 125 ± 10°, P = 0.003). No significant difference was noted in the degree of post-operative residual MR or functional MS between the groups. In a multivariate Cox proportional hazards analysis, the longer cardiopulmonary bypass time and the smaller post-operative aorto-mitral angle were independent predictors of the occurrence of AA during the follow-up period (odds ratio per 10 minutes 1.11; 95% CI 1.02-1.22, P = 0.019: odds ratio 0.91; 95% CI 0.85-0.98, P = 0.012).A small aorto-mitral angle at post-operative TTE was determined to be a predictor of new-onset AA after a mitral valve repair for treating MR.

[Dysphagia and Aspiration Pneumonia Caused by Kommerell's Diverticulum and the Vascular Ring Associated with Right-sided Aortic Arch:Report of a Case].

We report a case of an 80-year-old man complaining of dysphagia followed by aspiration pneumonia. Computed tomography of the chest revealed Kommerell's diverticulum associated with the right-sided aortic arch and the vascular ring which was formed by the aortic arch, the left subclavian artery, the ductus arteriosus, and the pulmonary artery around the esophagus and the trachea. Enlargement of the diverticulum was considered to be the cause of dysphagia. The surgery was performed at 20 ℃ under deep hypothermic circulatory arrest. We performed resection of the Kommerell's diverticulum, reconstruction of the left subclavian artery, and transection of the ductus arteriosus to relieve the compression by the esophagus and the trachea. The postoperative course was uneventful and dysphagia disappeared.

Etiology of Atrial Functional Mitral Regurgitation: Insights from Transthoracic Echocardiography in 159 Consecutive Patients with Atrial Fibrillation and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left atrial (LA) dilatation in patients with atrial fibrillation (AF) can induce functional mitral regurgitation (MR) despite a preserved left ventricular ejection fraction (LVEF). The purpose of this study was to investigate the etiology of this functional MR. METHODS: We retrospectively examined clinical and echocardiographic data from 5,202 consecutive cases that underwent transthoracic echocardiography. AF appeared in 544 patients, and we selected 159 with AF and LVEF ≥50% after excluding patients with other underlying heart diseases. RESULTS: Significant (moderate or greater) degrees of functional MR were seen in 13 (8.2%) patients and were more frequently seen in patients with an AF duration of >10 years than in others (27 vs. 4%, p = 0.0057). Multiple regression analysis revealed that both the LA dimension index and the left ventricular (LV) systolic dimension index were independent determinants of the MR grading. Among the mitral morphologic parameters, the mitral annular (MA) dimension index and the hamstringing phenomenon of the posterior mitral leaflet were independent determinants of MR grading. Significant MR was not seen in patients without LA dilatations, but it occurred in 14% of patients with LA dilatation alone and in 55% with both LA and LV dilatations; the MA dimension index increased in this order. CONCLUSIONS: The grading of functional MR occurring in patients with AF and preserved LVEF depends on both the LA dimension and the LV systolic dimension. The MR grading also depends on both the MA dilatation and the hamstringing phenomenon of the posterior mitral leaflet.

Successful Treatment of Staphylococcus schleiferi Infection after Aortic Arch Repair: In Situ Aortic Arch Replacement and Domino Reconstruction of the Debranching Graft using Autologous Iliac Artery.

A 62-year-old Japanese male presented with graft infection by Staphylococcus schleiferi 50 days after debranching of the left subclavian artery and frozen elephant trunk repair for the entry closure of a Stanford type B aortic dissection. The graft was removed, and the patient was successfully treated using in situ reconstruction of the arch with omental flap coverage, removal of the debranching graft, autologous iliac artery grafting, and longterm antibiotics. Domino reconstruction of the infected debranching graft using autologous external iliac artery and a Dacron graft can thus be a good option in similar cases.

[Repair for Atrial Functional Regurgitation of Atrio-ventricular Valves].

Persistent atrial fibrillation sometimes causes atrial enlargement. In such patients, regurgitation of mitral valve and tricuspid valve would be developed due to the enlargement of annulus of the atrio-ventricular valves. This mechanism of the mitral regurgitation is recently recognized as the atriogenic tethering of the posterior leaflet. Annuloplasty with ring is essential for the surgery in all patients. In the patients with giant left atrium, the annulus is tremendously enlarged. In such patients, we applied patch-augmentation of the posterior leaflet with autologous pericardial patch. Tricuspid annular dilatation is co-existed in these patients, so tricuspid annuloplasty should be done simultaneously. There is no guideline for the treatment of this pathology, so the indication for surgery should be argued.

Greater Nocturnal Blood Pressure Is Associated With Natriuretic Peptide Level in Aortic Stenosis With Preserved Ejection Fraction.

BACKGROUND: Although careful monitoring of asymptomatic severe aortic stenosis (AS) is recommended to prevent missing the optimal timing of surgical or transcatheter aortic valve replacement, prophylactic treatment that could extend the asymptomatic period remains unknown. In a hypertensive population, high blood pressure (BP) measured at the doctor's office is known to be associated with B-type natriuretic peptide (BNP) level, a surrogate marker for symptomatic deterioration in AS. Little is known regarding the association between nocturnal BP variables and BNP in severe AS with preserved ejection fraction (EF). Methods and Results: The subjects consisted of 78 severe AS patients (mean age, 79±6 years) with preserved EF. Nocturnal BP was measured hourly using a home BP monitoring device. On multiple regression analysis, nocturnal mean systolic BP (SBP) remained independently associated with BNP after adjustment for age, sex, body mass index, estimated glomerular filtration rate, antihypertensive medication class, early diastolic mitral annular velocity, and left ventricular mass index (P=0.03), whereas diastolic BP (DBP) and variables of BP variability were not. CONCLUSIONS: Higher nocturnal SBP rather than DBP or indices of BP variability was independently associated with BNP in AS patients with preserved EF. Intervention for nocturnal SBP may therefore extend the asymptomatic period and improve prognosis.

S-allyl-glutathione improves experimental liver fibrosis by regulating Kupffer cell activation in rats.

S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. We examined the potential preventive effects of SAG on acute and chronic models of liver fibrosis by chronic carbon tetrachloride (CCl4) administration. SAG inhibited liver fibrogenesis induced by CCl4 in a dose-dependent manner and reduced heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers. In fibrosis regression models, after administration of either CCl4 for 9 wk or dimethyl nitrosamine (DMN) for 6 wk, SAG markedly accelerated fibrolysis in both models. In the regression stage of DMN-treated liver, SAG normalized the ratio of M2 phenotype (expression of mannose receptor) in Kupffer cells (KCs). Consistent with these results, the culture supernatants of SAG-treated M2-phenotype KCs inhibited collagen-α1(I) chain (COL1A1) mRNA expression in primary culture-activated rat hepatic stellate cells (HSCs). However, SAG did not directly inhibit HSC activation. In an acute model of CCl4 single injection, SAG inhibited hepatic injury dose dependently consistent with the inhibited the elevation of the bilirubin and ALT levels. These findings suggest that SAG could improve the fibrogenic and fibrolysis cascade via the regulation of excess activated and polarized KCs. SAG may also serve as a preventive and therapeutic agent in fibrosis of other organs for which current clinical therapy is unavailable. NEW & NOTEWORTHY S-allyl-glutathione (SAG) is a metabolite of diallyl sulfide, a component of garlic. SAG increased hepatic glutathione levels and GSH-to-GSSG ratio in normal rats. SAG treatment before or after liver fibrosis from chronic CCl4 administration improved liver fibrosis and regression. SAG decreased heat shock protein-47 (HSP47), a collagen-specific chaperone, and other fibrosis markers in CCl4-treated livers. SAG-treated Kupffer cell conditioned medium also inhibited collagen-α1(I) chain (COL1A1) mRNA expression and other markers in primary culture hepatic stellate cells.

Prevalence and Prognostic Significance of Functional Mitral and Tricuspid Regurgitation Despite Preserved Left Ventricular Ejection Fraction in Atrial Fibrillation Patients.

BACKGROUND: We investigated the prevalence and prognostic significance of functional mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with atrial fibrillation (AF) and preserved left ventricular ejection fraction (LVEF).Methods and Results:We retrospectively studied the cases of 11,021 consecutive patients who had undergone transthoracic echocardiography. AF appeared in 1,194 patients, and we selected 298 with AF and LVEF ≥50% but without other underlying heart diseases. Moderate or greater (significant) degree of functional MR and of TR was seen in 24 (8.1%) and in 44 (15%) patients, respectively (P=0.0045). In contrast, significant MR and TR were more frequently seen in patients with AF duration >10 years (28% vs. 25%, respectively). During the follow-up period of 24±17 months, 35 patients (12%) met the composite endpoint defined as cardiac death, admission due to heart failure, or mitral and/or tricuspid valve surgery. On Cox proportional hazard ratio analysis, both MR and TR grading predicted the endpoint, independently of other echocardiographic parameters. On Kaplan-Meyer analysis, presence of both significant functional MR and TR was associated with poor prognosis, with an event-free rate of only 21% at the mean follow-up period of 24 months. CONCLUSIONS: Significant functional MR and TR are seen in a substantial proportion of patients with longstanding AF, despite preserved LVEF. This MR/TR combination predicts poor outcome for AF patients, who may have to be treated more intensively.

Echocardiographic parameters predicting acute hemodynamically significant mitral regurgitation during transfemoral transcatheter aortic valve replacement.

BACKGROUND: Alteration in mitral valve morphology resulting from retrograde stiff wire entanglement sometimes causes hemodynamically significant acute mitral regurgitation (MR) during transfemoral transcatheter aortic valve replacement (TAVR). Little is known about the echocardiographic parameters related to hemodynamically significant acute MR. METHODS AND RESULTS: This study population consisted of 64 consecutive patients who underwent transfemoral TAVR. We defined hemodynamically significant acute MR as changes in the severity of MR with persistent hypotension (systolic blood pressure < 80-90 mm Hg or mean arterial pressure 30 mm Hg lower than baseline). Hemodynamically significant acute MR occurred in 5 cases (7.8%). Smaller left ventricular end-systolic diameter (LVDs), larger ratios of the coiled section of stiff wire tip to LVDs (wire-width/LVDs), and higher Wilkins score were significantly associated with hemodynamically significant acute MR (P < .05), whereas the parameters of functional MR (annular area, anterior-posterior diameter, tenting area, and coaptation length) were not. Moreover, when patients were divided into 4 groups according to wire-width/LVDs and Wilkins score, the group with the larger wire-width/LVDs and higher Wilkins score improved prediction rates (P < .05). CONCLUSIONS: Small left ventricle or wire oversizing and calcific mitral apparatus were predictive of hemodynamically significant acute MR. These findings are important for risk stratification, and careful monitoring using intraoperative transesophageal echocardiography may improve the safety in this population.

Carbon monoxide-releasing molecule, CORM-3, modulates alveolar macrophage M1/M2 phenotype in vitro.

Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess the modulation of M1/M2 phenotype in alveolar macrophages by water-soluble carbon monoxide-releasing molecule-3 (CORM-3). Rat alveolar macrophages (AM) (NR8383) in culture were stimulated with LPS (5 ng/ml)/IFN-γ (10 U/ml) or IL-4 (10 ng/ml)/IL-13 (10 ng/ml) to induce M1 and M2 phenotypes, respectively. Expression of M1 phenotype markers, iNOS and TNF-α, and M2 phenotype markers, CD206 and Ym-1, was assessed by western blotting after 1, 3, 6, or 24 h in the absence or presence of CORM-3 (0.15 mM) treatment. Inactive CORM-3 (iCORM-3) was used as a control. Treatment of naïve (unstimulated) AM with CORM-3 promoted progression of the M2 phenotype as evidenced by the increased expression of CD206 (at 1 h; 1.8-fold) and Ym-1 (at 3 h; 1.9-fold), respectively. Surprisingly, CORM-3 treatment also upregulated the expression of iNOS protein as assessed 6 h following stimulation of AM with CORM-3 (2.6-fold). On the contrary, CORM-3 effectively reduced LPS/IFN-γ-induced expression of iNOS protein (0.6-fold); however, it had no effect on TNF-α expression. Finally, CORM-3 acutely (1-3 h) upregulated CD206 (1.4-fold) and Ym-1 (1.6-fold) levels in IL-4-/IL-13-treated (M2-stimulus) macrophages. These findings indicate that CORM-3 modulates macrophage M1 and M2 phenotypes in vitro with respect to continuous suppression of iNOS expression in M1-polarized macrophages and transient (early-phase) upregulation of CD206 and Ym-1 proteins in M2-polarized macrophages.

Pirfenidone suppresses polarization to M2 phenotype macrophages and the fibrogenic activity of rat lung fibroblasts.

Pirfenidone is a representative medication to treat interstitial pulmonary fibrosis. Researchers reported pirfenidone (>100 µg/ml) significantly suppressed fibroblast growth in vitro. However, clinically, the maximum concentration of pirfenidone in the blood is approximately 10 µg/ml. We hypothesized there might be an additional mechanism of pirfenidone to fibroblasts indirectly. Macrophages are known to control the activation of fibroblasts via the regulation of inflammatory M1 and suppressive M2 polarization. The aim of this study was to investigate the effects of pirfenidone on alveolar macrophage polarization. Rat alveolar macrophages (NR8383) were stimulated in vitro with lipopolysaccharide (LPS) + interferon (IFN)-γ, or interleukin (IL)-4 + IL-13. Expression of M1 and M2 markers and supernatant's levels of TGF-ß1 were assessed after pirfenidone treatment (0-100 µg/ml). Treatment with LPS + INF-γ or IL-4 + IL-13 significantly increased the expression of M1 and M2 markers, respectively. In macrophage polarization assays, pirfenidone significantly reduced the expression of M2 markers at concentrations greater than 10 µg/ml but had no effect on the expression of M1 markers. At these concentrations, pirfenidone significantly reduced TGF-ß1 levels in NR8383 culture supernatants. In rat lung fibroblasts treated with NR8383 culture supernatants, pirfenidone significantly suppressed proliferation, and the collagen mRNA and protein levels. In conclusion, our results demonstrated that pirfenidone suppressed polarization to M2 macrophages at clinically relevant concentrations and suppressed the rat lung fibroblasts fibrogenic activity.