Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes.

Genetic mutations in actin regulators have been emerging as a cause of cardiomyopathy, although the functional link between actin dynamics and cardiac contraction remains largely unknown. To obtain insight into this issue, we examined the effects of pharmacological inhibition of formins, a major class of actin-assembling proteins. The formin inhibitor SMIFH2 significantly enhanced the cardiac contractility of isolated frog hearts, thereby augmenting cardiac performance. SMIFH2 treatment had no significant effects on the Ca2+ sensitivity of frog muscle fibers. Instead, it unexpectedly increased Ca2+ concentrations of isolated frog cardiomyocytes, suggesting that the inotropic effect is due to enhanced Ca2+ transients. In contrast to frog hearts, the contractility of mouse cardiomyocytes was attenuated by SMIFH2 treatment with decreasing Ca2+ transients. Thus, SMIFH2 has opposing effects on the Ca2+ transient and contractility between frog and mouse cardiomyocytes. We further found that SMIFH2 suppressed Ca2+ -release via type 2 ryanodine receptor (RyR2); this inhibitory effect may explain the species differences, since RyR2 is critical for Ca2+ transients in mouse myocardium but absent in frog myocardium. Although the mechanisms underlying the enhancement of Ca2+ transients in frog cardiomyocytes remain unclear, SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling.

Endoscopic filling with polyglycolic acid sheets and fibrin glue of persistent fistula after esophagectomy.

BACKGROUND: Treatment of anastomotic leakage in reconstruction after esophagectomy remains challenging. This report presents a new endoscopic filling method for persistent fistula after failure of conservative treatment of leakage caused by anastomotic insufficiency. METHODS: 10 of 14 patients, in whom post-esophagectomy leakage had failed to resolve after 2 weeks of conservative treatment, underwent endoscopic filling with polyglycolic acid (PGA) sheet and fibrin glue into the anastomotic leakage site, using a delivery tube and endoscopic catheter, respectively. RESULTS: Each patient underwent jejunostomy, to secure nutrition. The leakage was resolved in all 10 patients. The mean number of PGA - fibrin glue procedures was 1.7. The mean period from the first application to the resumption of oral intake was 31.6 days, from the final application it was 14.7 days. CONCLUSIONS: The reported filling method offers a new endoscopic approach for persistent fistula after esophagectomy when conservative treatment of leakage has failed.

Influence of preoperative right ventricular function on left ventricular remodeling and survival after subvalvular repair for functional mitral regurgitation.

OBJECTIVES: The objective of this study was to analyze our surgical experiences with mitral valve plasty (MVP) combined with subvalvular procedures (SVPs) for functional mitral regurgitation (FMR) and to determine which preoperative factors affected clinical outcomes. METHODS: This study retrospectively analyzed 33 patients who underwent MVP combined with SVPs for FMR with a left ventricular ejection fraction lower than 40% and advanced remodeled left ventricles. The mean follow-up period was 49 ± 33 months. RESULTS: The preoperative mean right ventricular fractional area change (RVFAC) used to quantify right ventricular (RV) systolic function was 26 ± 11%. Sixteen patients (48%) had an RVFAC < 26%. One patient died during hospital stay, and nine more patients died of cardiac causes during follow-up. The 3- and 5-year rates of freedom from cardiac-related mortality were 78% and 68%, respectively. RVFAC was the significant predictor of cardiac-related mortality in a univariate analysis (risk ratio [RR] = 0.92, 95% confidence interval [CI] 0.85-0.99, p = 0.03) and demonstrated a non-significant tendency to predict cardiac-related mortality in the Cox multivariate analysis (RR = 0.94, 95% CI 0.86-1.003, p = 0.08). Continued reverse left ventricular remodeling was associated with an RVFAC ≥ 26%. At 3 years, there was also a significant difference in survival rates of cardiac-related mortality between patients with an RVFAC ≥ 26% and < 26% (94% vs. 61%; p = 0.03). CONCLUSIONS: Preoperative RV function affected left ventricular remodeling and cardiac-related mortality after MV surgery. MVP combined with SVPs for FMR provided promising results for patients without severe RV dysfunction.

Current status of trauma surgery at a Japanese prefectural academic institute: improved organization in a regional prefecture.

PURPOSES: Balancing scheduled surgery and trauma surgery is difficult with a limited number of surgeons. To address the issues and systematize education, we analyzed the current situation and the effectiveness of having a trauma team in the ER of a regional hospital. METHODS: This retrospective study analyzed the demographics, traumatic variables, procedures, postoperative morbidities, and outcomes of 110 patients who underwent trauma surgery between 2012 and 2019. The trauma team was established in 2016 and our university hospital Emergency Room (ER) opened in 2012. RESULTS: Blunt trauma accounted for 82% of the trauma injuries and 39% of trauma victims were transported from local centers to our institute. The most frequently injured organs were in the digestive tract and about half of the interventions were for hemostatic surgery alone. Concomitant treatments for multiple organ injuries were performed in 31% of the patients. The rates of postoperative severe complications (over Clavien-Dindo IIIb) and mortality were 10% and 13%, respectively. Fourteen (12.7%) of 24 patients who underwent damage-control surgery died, with multiple organ injury being the predominant cause of death. CONCLUSION: Systematic education or training of medical students and general surgeons, as well as the co-operation of the team at the regional academic institute, are necessary to overcome the limited human resources and save trauma patients.

Relationship between hepatic venous anatomy and hepatic venous blood loss during hepatectomy.

PURPOSE: Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy. METHODS: We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined. RESULTS: The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5 mL/kg) were tumor size (> 4 cm), prothrombin activity (< 87%), CVP (> 7 mmHg), area of suprahepatic IVC (< 360 mm2), IVC-RA gap (> 28 mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases. CONCLUSION: The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy.

Utility of thoracic cage width in assessing surgical difficulty of minimally invasive esophagectomy in left lateral decubitus position.

BACKGROUND: This study aimed to assess the surgical difficulty of minimally invasive esophagectomy in the left lateral decubitus position for patients with esophageal cancer from the perspective of short-term outcomes, including operation time, blood loss, and morbidity. MATERIALS AND METHODS: The initial 44 consecutive patients with esophageal cancer who underwent minimally invasive esophagectomy were statistically analyzed retrospectively. Thoracic cage area was measured from preoperative computed tomography as a factor affecting the surgical difficulty of minimally invasive esophagectomy, as well as other patient characteristics. Correlations with short-term outcomes including chest operation time, blood loss, and morbidity rate were then examined. RESULTS: In univariate analyses, smaller area of the upper thoracic cage width correlated with prolonged thoracic procedure time (p = 0.0119) and greater blood loss during thoracic procedures (p = 0.0283), but area of the lower thoracic cage showed no correlations. History of respiratory disease was associated with thoracic procedure time (p < 0.0001), but not blood loss. In multivariate analysis, small area of the upper thoracic cage was independently associated with prolonged thoracic procedure time (p = 0.0253). Small upper thoracic cage area was not directly correlated with morbidity rate, but prolonged thoracic procedure time was associated with increased blood loss (p < 0.0001) and morbidity rate (p = 0.0204). Empirical time reduction (p = 0.0065), but not blood loss, was associated with thoracic procedure time. However, area of the upper thoracic cage did not correlate with empirical case number. In multivariate analysis, area of the upper thoracic cage (p = 0.0317) and empirical case number (p = 0.0193) correlated independently with thoracic procedure time. CONCLUSION: A small area of the upper thoracic cage correlated significantly with prolonged thoracic procedure time and increased thoracic blood loss for minimally invasive esophagectomy in the left lateral decubitus position, suggesting the surgical difficulty of minimally invasive esophagectomy in the left lateral decubitus position.

Aortoesophageal fistula: review of trends in the last decade.

We reviewed articles on aortoesophageal fistula (AEF) published between January, 2009 and December, 2018. Postoperative aortic disease was the most common cause of AEF, followed by primary aortic aneurysm, bone ingestion, and thoracic cancer. Thoracic endovascular aortic repair (TEVAR) was the most common initial therapy for primary aortic disease, rather than graft replacement. Secondary AEF developed between 1 and 268 months, and between 1 and 11 months after the initial therapy for aortic disease and thoracic cancer, respectively. TEVAR trended to be preferred over surgery for aortic lesions because of its minimal invasiveness and certified hemostasis. In contrast, esophagectomy was preferred for esophageal lesions to remove the infectious source. A combination of surgery for the aorta (TEVAR, graft replacement or repair) and esophagus (esophagectomy, esophageal stent or repair) was usually adopted. Each graft replacement or esophagectomy was associated with a favorable prognosis for aortic or esophageal surgery, and the combination of graft replacement and esophagectomy generally improved the prognosis remarkably. Antibiotic therapy was given to 65 patients, with 20 receiving multiple antibiotics aimed at strong effects and the type of antibiotic described as broad-spectrum in 29 patients. Meropenem, vancomycin, and fluconazole were the most popular antibiotics used to prevent graft or stent infection. In conclusion, graft replacement and esophagectomy can achieve a favorable prognosis for patients with AEF, but strong, broad-spectrum antibiotic therapy might be required to prevent sepsis after surgery.

[Preoperative Spontaneous Regression of Thymoma].

We report a case of preoperative spontaneous regression of thymoma in a 66-year-old woman who presented chest pain. Chest computed tomography revealed a well-defined tumor in the anterior mediastinum. The long axis of the tumor decreased from 25 to 18 mm during 1 month preoperatively. Video-assisted thoracoscopic thymothymectomy was performed for definitive diagnosis and treatment. Histopathologically, the tumor mainly comprised necrotic components with partially viable cells, and was diagnosed as a thymoma. The occlusion of the feeding artery by organized thrombus was found by pathology and it was considered to be the cause of coagulative necrosis.

Diabetes Mellitus Induces Hyperreactivity of 5-Hydroxytryptamine (5-HT)-Induced Constriction in Human Internal Thoracic Artery and Is Associated with Increase in the Membrane Protein Level of 5-HT2A Receptor.

Studies indicate that 5-hydroxytryptamine (5-HT) released from activated platelets in coronary artery bypass grafting (CABG) induces 5-HT2A receptor-mediated graft spasm. We previously reported that 5-HT-induced constriction of human endothelium-denuded saphenous vein (SV) was significantly augmented in patients with diabetes mellitus (DM) than in patients without DM (non-DM), without changes in the levels of the membrane-bound 5-HT2A receptor of their smooth muscle cells. Although the internal thoracic artery (ITA) is the key graft conduit for CABG, the effect of DM on the ITA graft spasm is still unclear. Therefore, in this study, we investigated the effect of DM on 5-HT-induced vasoconstriction and the level of membrane-bound 5-HT2A receptor in ITA grafts. 5-HT-induced constriction of the isolated human endothelial-denuded ITA was significantly higher in patients with DM than in patients without DM. In addition, the level of the 5-HT2A receptor in the membrane fraction of human ITA smooth muscle cells was significantly higher in patients with DM than in those without DM. These results demonstrate that DM is a risk factor for CABG in both venous and arterial conduits, and that it differentially affects the level of the membrane-bound 5-HT2A receptor in the venous and arterial smooth muscle cells.

Comparison of mitral competence after mitral repair with papillary muscle approximation versus papillary muscle relocation for functional mitral regurgitation.

The purpose of this study was to evaluate the surgical results of papillary muscle approximation (PMA) and papillary muscle relocation (PMR) for functional mitral regurgitation (FMR) and to compare the effects of both procedures on the change in mitral regurgitation (MR) and echocardiogram parameters associated with tethering. Eighteen patients with moderate-to-severe FMR (MR grade ≥2) who underwent PMA or PMR were retrospectively analyzed. Underlying diseases were ischemic cardiomyopathy, idiopathic dilated cardiomyopathy, and aortic valve disease for seven, six, and five patients, respectively. Eleven patients underwent PMA and seven patients underwent PMR. Mitral annuloplasty and surgical ventricular restoration were performed concomitantly for 18 and 6 patients, respectively. None of these patients died in the hospital. Three patients died during the late period; two of these deaths were cardiac related. The rate of 3 years of freedom from cardiac-related death was 89%. After a mean follow-up of 33 months, MR grade was significantly improved compared with preoperative values (3.0 ± 0.8 to 0.7 ± 1.2; p < 0.01). Recurrence of MR grade ≥2 occurred in three patients and the rate of 3 years of freedom from recurrence of MR grade ≥2 was 87%. During follow-up, tenting height (1.1 ± 0.2 to 0.7 ± 0.2 cm; p < 0.01), tenting area (2.2 ± 0.7 to 0.9 ± 0.5 cm2; p < 0.01), and anterior leaflet tethering angle (39° ± 11° to 26° ± 8°; p < 0.01) were significantly improved compared with preoperative values. Posterior leaflet tethering angle significantly deteriorated from 40° ± 7° to 53° ± 15° (p < 0.01); however, it did not further deteriorate compared with the early postoperative value of 55° ± 16° (p = 0.7). There was no difference in echocardiogram parameters associated with tethering between PMA and PMR throughout the observation period. Both methods were associated with lasting relief of MR and reverse left ventricular remodeling. There was no difference between PMA and PMR regarding the effect on mitral valve competence. Both methods allowed durable mitral repair and good clinical outcomes.

Fluorodeoxyglucose Positron Emission Tomography Can Provide Useful Information for Differentiating Thymic Epithelial Tumors.

BACKGROUND: We examined the usefulness of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting the World Health Organization (WHO) histologic type and Masaoka stage of thymic epithelial tumors. METHODS: A total of 73 patients with thymic epithelial tumors who underwent preoperative FDG-PET were included. Relationships between the maximum standardized uptake value (SUVmax) and WHO histologic type and the Masaoka stage of the tumor were examined. Differences in SUVmax between the various groups were calculated. To avoid the effect of the tumor size on SUVmax, the ratio of SUVmax to tumor size (SUVmax/T) was also examined. RESULTS: There was a significant relationship between SUVmax and WHO histologic type. SUVmax of high-risk thymomas (types B2 and B3) was significantly higher than that of low-risk thymomas (types A, AB, and B1). SUVmax of thymic carcinomas was also significantly higher than those of the low-risk and high-risk groups. The relationship between the SUVmax/T and WHO histologic type showed more significant results. SUVmax and SUVmax/T showed higher values in patients with advanced Masaoka stage disease than in those with early-stage disease. CONCLUSIONS: FDG-PET can provide useful information for differentiating thymic epithelial tumors. The SUVmax/T is more useful than the SUVmax for differentiating between low-risk and high-risk thymomas.

Primary pulmonary angiosarcoma: A case report.

Primary sarcoma is uncommon in the lung, and primary angiosarcoma is exceedingly rare. We report a case of primary pulmonary angiosarcoma of the left lung with emphasis on its growth pattern in the lung. A 48-year-old Japanese man was admitted to our hospital because of dyspnea on exertion. He was subsequently found to have left pleural effusion. Computed tomography shows a nodular lesion measuring 7 × 4 cm in his left lung. Obstruction of the left inferior lobar bronchus was observed, and endobronchial biopsy suggested angiosarcoma. Left pneumonectomy was performed. On macroscopic examination of the cut surface, multiple nodular lesions were observed particularly in portions around branches of pulmonary artery along bronchioles. Histological examination revealed vascular channel-like structure with vague lumen formations by atypical polygonal or spindle-shaped neoplastic cells. Immunohistochemically, the neoplastic cells are positive for FLI-1, ERG, CD31 and von Willebrand factor/factor VIII-related antigen, but not CD34. Angiosarcoma is a particularly rare form of primary pulmonary tumors, and this case report describes its unique macroscopic growth pattern in the lung.

[Mitral valve replacement for a manifesting carrier of duchenne muscular dystrophy].

Duchenne muscular dystrophy (DMD) is an X-linked disease, but female carriers infrequently have some symptoms, who are called manifesting carriers. Here we report a case of a manifesting carrier of DMD with skeletal muscle weakness and cardiac abnormalities such as deterioration of cardiac function and left ventricular dilatation, who successfully underwent cardiac surgery. A 79-year-old female with acute heart failure for severe mitral regurgitation was admitted to our hospital. Surgical replacement of the mitral valve was performed under general anesthesia with intravenous anesthetics and non-depolarizing muscle relaxant. Cardiac surgery on a manifesting carrier of DMD is rare and requires a careful preoperative assessment of the heart function and anesthetic management.

[Aortic Root Reimplantation for Extra-cardiac Unruptured Sinus of Valsalva Aneurysm].

Aneurysms of the sinus of Valsalva are rare. We report a case of extra-cardiac unruptured aneurysm of the sinus of Valsalva with moderate aortic regurgitation (AR). A 57-year-old woman was referred to our institution because of AR. Echocardiography showed moderate AR and computed tomographic scanning demonstrated an extra-cardiac aneurysm of the unruptured sinus of Valsalva, which extended from the right sinus of Valsalva to the non-coronary sinus of Valsalva. She underwent aortic root reimplantation procedure with a Valsalva graft. Although mild AR was observed postoperatively, her postoperative course was uneventful.

[A case of long-term survival after low-dose FP systemic chemotherapy for a tumor thrombus in the inferior caval vein and multiple lung metastases from recurrent hepatocellular carcinoma].

We report a case of long-term survival of a patient who received low-dose 5-fluorouracil and cisplatin (FP) systemic chemotherapy and underwent partial resection of the lung for a tumor thrombus in the inferior caval vein (IVC) and multiple lung metastases from recurrent hepatocellular carcinoma (HCC). The patient was a 66-year-old man who was admitted to our hospital for the treatment of a 13-cm liver tumor. He underwent an extended posterior sectionectomy of the liver. Pathological diagnosis revealed moderately differentiated hepatocellular carcinoma (vp1, vv1, sm[-, 1.5mm], ch, T3N0M0, stage III). At 3 months postoperatively, computed tomography (CT) revealed a tumor thrombus in the IVC and multiple (>20) lung tumors that were considered HCC recurrences. Low-dose FP systemic chemotherapy was initiated, and the tumors reduced in size. However, a new lesion in the left lung was detected at 13 months postoperatively. Thoracoscopyassisted resection of the tumor that was histologically diagnosed as an HCC metastasis was performed at 26 months postoperatively. The patient is cancer free at 46 months postoperatively. Therefore, low-dose FP systemic chemotherapy is one of the therapeutic options for the treatment of HCC recurrences of IVC tumor thrombi and multiple lung metastases. However, the occurrence of new lesions should be carefully monitored.

[Parasternal approach for anterior apical lung cancer with invasion of the first rib].

For complete resection of anterior apical invasive lung cancer, it is of clinical significance to select the appropriate surgical approaches based on the anatomic location of the tumor and extent of invasion of adjacent anatomic structures. However, patients with anterior apical lung cancer without vessel invasion are occasionally burdened with unnecessarily excessive surgical invasion. We present 2 cases of anterior apical lung cancer invading the 1st rib but not subclavian vein, who underwent complete resection through the parasternal approach. We also discuss the feasibility of this approach.

Knowledge survey regarding blast wound education of student doctors at a local academic medical university in Japan.

Objectives: To improve knowledge about blast injury for medical student doctors or surgeons. In the modern uncertain era, education and training programs for blast injuries for medical student doctors or surgeons are recently necessary worldwide. Material and Methods: To understand primary corresponding ability to treat blast injuries, leading to improvement of the trauma education curriculum, a retrospective study by a knowledge survey was performed between 2018 and 2019. The subject had the title of Student Doctor (SD) at university. Results: The answers of 183 participants who answered the interview questionnaire with 16 questions were summarized. Although most SDs received basic lectures for trauma medicine and majority of SDs knew about mass casualty incidents and primary treatment, the existence of knowledge on soft targets is limited. One-fourth of the SDs knew the characteristics of blast wounds. Most SDs understood priority triage for a conscious person with massive bleeding from a limb with hemostasis to save lives. The 17% selected cardiopulmonary resuscitation first and 72% of SDs could explain hemorrhagic shock; however, only four could explain adequate hemostatic procedures. Most had no interest regarding necessity of their knowledge in the field of serious blast trauma wounds. Conclusion: Experience in trauma surgery training from stages in SDs and authorized education are important for raising students' knowledge of unexpected serious blast incidents.

Clinical Outcomes of a Customized Mitral Valve Plasty for Functional Mitral Regurgitation with a Low Ejection Fraction and Implications for Preoperative Right Ventricular Function.

PURPOSE: To evaluate clinical outcomes of customized mitral valve plasty (MVP) for the treatment of functional mitral regurgitation (FMR) with a low ejection fraction (EF) and to determine which preoperative factors affected the clinical outcome. METHODS AND RESULTS: MVP was adjusted according to the degree of left ventricle (LV) remodeling. We performed mitral annuloplasty (MAP) alone in 14 patients and added subvalvular procedures (SVPs) in 22 patients at a high risk of recurrent MR. During follow-up, reverse LV remodeling was obtained and the 3-year and 5-year non-recurrence rates of MR grade ≥2 were 94% and 89%, respectively. Two patients died during their hospital stay, and four more patients died of cardiac causes during follow-up. The 3-year and 5-year rates of freedom from cardiac-related mortality were 86% and 81%, respectively; no significant difference was observed between the two treatment groups. Right ventricular fractional area change (RVFAC) was a significant predictor of cardiac mortality. Patients with an RVFAC of <26% had significantly poorer cardiac-related mortality (71% at 3 years) than those with an RVFAC of ≥26% (95% at 3 years). CONCLUSION: Customized MVP provided durable mitral competence and reverse LV remodeling. Preoperative RV function was associated with cardiac-related mortality.

Successful treatment of left ventricular patch infection by latissimus dorsi muscle flap covering without patch removal.

Removal of the infected prosthesis is considered an essential procedure in the treatment of prosthetic graft infection following cardiovascular surgery. Here, we present a case of left ventricular patch infection following repair of left ventricular rupture that was successfully treated by coverage with a latissimus dorsi muscle flap without patch removal. A 61-year-old man underwent double-patch repair for left ventricular-free wall rupture following posterior myocardial infarction. He underwent drainage and omental transposition with re-sternotomy for postoperative mediastinitis by Candida albicans, followed by pericardial fenestration via left thoracotomy for infectious pericarditis; however, left ventricular patch infection was detected. Considering the high invasiveness of a reoperation for patch removal, we preserved and covered the patch using a left pedicled latissimus dorsi muscle flap via left thoracotomy. The postoperative course was uneventful, and the patient was asymptomatic with no signs of recurrence at 30 months.

Upregulated Kynurenine Pathway Enzymes in Aortic Atherosclerotic Aneurysm: Macrophage Kynureninase Downregulates Inflammation.

AIMS: Inflammation and hypertension contribute to the progression of atherosclerotic aneurysm in the aorta. Vascular cell metabolism is regarded to modulate atherogenesis, but the metabolic alterations that occur in atherosclerotic aneurysm remain unknown. The present study aimed to identify metabolic pathways and metabolites in aneurysmal walls and examine their roles in atherogenesis. METHODS: Gene expression using microarray and metabolite levels in the early atherosclerotic lesions and aneurysmal walls obtained from 42 patients undergoing aortic surgery were investigated (early lesion n=11, aneurysm n=35) and capillary electrophoresis-time-of-flight mass spectrometry (early lesion n=14, aneurysm n=38). Using immunohistochemistry, the protein expression and localization of the identified factors were examined (early lesion n=11, non-aneurysmal advanced lesion n=8, aneurysm n=11). The roles of the factors in atherogenesis were analyzed in macrophages derived from human peripheral blood mononuclear cells. RESULTS: Enrichment analysis using 35 significantly upregulated genes (log2 ratio, ＞3) revealed the alteration of the kynurenine pathway. Metabolite levels of tryptophan, kynurenine, and quinolinic acid and the kynurenine-to-tryptophan ratio were increased in the aneurysmal walls. Gene and protein expression of kynureninase and kynurenine 3-monooxygenase were upregulated and localized in macrophages in the aneurysmal walls. The silencing of kynureninase in the cultured macrophages enhanced the expression of interleukin-6 and indoleamine 2,3-dioxygenase 1. CONCLUSION: Our study suggests the upregulation of the kynurenine pathway in macrophages in aortic atherosclerotic aneurysm. Kynureninase may negatively regulate inflammation via the kynurenine pathway itself in macrophages.