Background/Objectives: Monitored anesthesia care (MAC) is increasingly used for transcatheter aortic valve replacement (TAVR), where rapid recovery of consciousness may facilitate early postoperative neurological assessment. Remimazolam provides sedation that can be pharmacologically reversed with flumazenil. We compared emergence from sedation between a remimazolam–flumazenil-based MAC strategy and a conventional dexmedetomidine-based strategy in patients undergoing transfemoral TAVR. Methods: In this single-center randomized controlled trial, 84 patients undergoing transfemoral TAVR were randomized 1:1 to remimazolam–remifentanil (R group) or dexmedetomidine–propofol–remifentanil (D group) MAC. Flumazenil was administered at the initiation of the postoperative awakening attempt in the R group. The primary outcome was arousal time, assessed using two prespecified measures: time from discontinuation of all anesthetic infusions to arousal and time from initiation of the postoperative awakening attempt to arousal. Arousal was defined as a Modified Observer’s Assessment of Alertness/Sedation score of 5. Results: Eighty-three patients were included in the analysis (R group, n = 42; D group, n = 41). The time from discontinuation of all anesthetic infusions to arousal was shorter in the R group than in the D group (19.05 [15.77–23.59] vs. 24.09 [19.25–34.78] min; p = 0.0045). The time from initiation of the awakening attempt to arousal was also shorter (0.60 [0.33–1.00] vs. 1.00 [0–4.72] min; p = 0.0117). No patient in the R group required rescue propofol. No significant between-group differences were observed in major procedural or postoperative outcomes. Conclusions: A remimazolam-based MAC strategy with flumazenil reversal provided faster and more reliable emergence from sedation than a conventional dexmedetomidine-based strategy during transfemoral TAVR. These findings suggest that a reversible sedation strategy may facilitate rapid recovery of consciousness when early postoperative assessment is desired, although its impact on neurological or other clinical outcomes remains to be established.

PURPOSE: This study characterized nationwide trends, demographic distributions, and regional disparities in cardiac anesthesia and intraoperative transesophageal echocardiography (ITEE) in Japan. METHODS: We conducted a retrospective observational study using the National Database of Health Insurance Claims (NDB) Open Data Japan (2019-2023). Cardiac anesthesia was defined using reimbursement codes for cardiac or thoracic great-vessel surgery requiring cardiopulmonary bypass. ITEE was evaluated using add-on claims classified into two categories: ITEE for cardiac/non-cardiac surgeries, and ITEE for percutaneous interventions. Trends were assessed using linear and Poisson regression models. Age- and sex-specific distributions and regional disparities (Gini coefficients) were assessed. RESULTS: A total of 179,920 cardiac anesthesia events were identified (28.7 per 100,000 person-years), with a male predominance (male-to-female ratio, 1.6:1). Age distribution was bimodal, peaking at 0-4 and 75-79 years. Both cardiac anesthesia and ITEE use declined transiently during Japan's first coronavirus disease 2019 state of emergency in May 2020, followed by recovery in the latter half of fiscal year 2020. Age-adjusted rates of cardiac anesthesia demonstrated no significant annual change. In contrast, ITEE use increased significantly in both cardiac/non-cardiac surgeries (relative risk [RR], 1.011/year; P < 0.0001) and percutaneous interventions (RR, 1.117/year; P < 0.0001). Regional disparities in cardiac anesthesia decreased over time, with Gini coefficients declining from 0.20 to 0.15. CONCLUSION: Cardiac anesthesia remained generally stable in Japan from 2019 to 2023. Increasing ITEE, especially for percutaneous interventions, suggests evolving cardiovascular perioperative practice, although claims-based categories require cautious interpretation.

Thioredoxin‑interacting protein (Txnip), a member of α‑arrestin superfamily, is best known for inhibiting thioredoxins and glucose transporters, increasing oxidative and metabolic stress. Through these functions, Txnip has emerged as a key contributor to the pathogenesis of heart diseases. Txnip contains C‑terminal PPXY motifs that are conserved among α‑arrestins across diverse species. Nevertheless, the physiological significance of these motifs remains unknown. We demonstrate that mutation of Txnip PPXY motifs to AAXA uncouples Txnip's canonical functions from its cytotoxic effects. While the mutant reduced glutathione levels and glucose uptake to the same extent as wild‑type Txnip, it attenuated cell death. To assess translational relevance, we engineered inducible, cardiomyocyte‑restricted Txnip PPXY‑to‑AAXA knock‑in mice. These mice displayed normal cardiac structure and function at baseline but were strongly protected after myocardial infarction, exhibiting improved left ventricular performance and overall survival. Mechanistically, structural modeling identified the E3 ubiquitin ligase ITCH as the principal PPXY‑binding partner. The PPXY mutation abolished Txnip ubiquitination and stabilized Txnip protein, revealing a paradoxical dissociation between Txnip levels and cardiotoxicity. Transcriptomic profiling uncovered enrichment of PPAR‑α/PGC‑1α-associated pathways, although metabolic assays and untargeted lipidomics did not support these findings. Instead, immediate early genes of the Fos/Jun AP‑1 network were consistently downregulated after ischemic injury, and AP‑1 DNA‑binding activity was diminished in PPXY mutant hearts. These results identify the Txnip PPXY motifs as key regulators of Txnip protein turnover and injury‑responsive transcriptional programs. Disruption of these motifs stabilizes Txnip yet confers cardioprotection, providing evidence that elevated Txnip levels do not invariably drive cardiotoxicity.

BACKGROUND: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti-inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti-inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti-inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. METHODS: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. RESULTS: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C-reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p = .014). CONCLUSIONS: Remimazolam exerted stronger anti-inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production.

Remimazolam, an ultrashort-acting benzodiazepine, allows for rapid and reliable arousal. Rapid awakening using remimazolam may be beneficial in transcatheter aortic valve replacement (TAVR), as it allows rapid detection of neurologic deficits. The purpose of this study was to compare arousal time and outcomes between monitored anesthesia care (MAC) with remimazolam and remifentanil and conventional MAC with dexmedetomidine, propofol, and remifentanil. This study was a single center retrospective study. All TAVR cases performed under MAC (MAC-TAVR) at our institution between 2019 and 2021 were included. Patients were classified by anesthesia method into remimazolam and dexmedetomidine groups. Among 258 MAC-TAVR patients, 253 were enrolled. After propensity score matching, 76 patients were assigned to each group. The time from end of drug-administration to arousal [20.0 (16.0, 24.0) min vs. 38.5 (30.0, 56.3) min, p < 0.0001] and the time from attempted-arousal to arousal [1.0 (1.0, 1.0) min vs. 12.5 (3.0, 26.8) min, p < 0.0001] were significantly shorter in the remimazolam group. There was no significant difference in the length of ICU stay [2.0 (2.0, 2.0) days vs. 2.0 (2.0, 2.0) days, p = 0.157] and postoperative hospital stay [6.0 (4.0, 9.0) days vs. 5.0 (4.0, 8.0) days, p = 0.262].Trial registration: Clinical trial number: R03-123, Registry URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051635 Registration number: UMIN000045195, Principal investigator's name: Atsuhiro Kitaura, Date of registration: 20 August 2021.

Andexanet alfa is an analog of activated factor X and is used as an antagonist of anti-activated factor X agents. Andexanet alfa is useful for hemostasis in emergent bleeding during direct oral anticoagulant administration, which contributes to safety. In patients undergoing surgery with cardiopulmonary bypass because of heparin resistance, anesthesiologists are faced with a choice of anticoagulants. Herein, we experienced anesthesia for vascular prostheses with cardiopulmonary bypass for acute aortic dissection in a patient who had received andexanet alfa preoperatively. Heparin was initially used as the anticoagulant during cardiopulmonary bypass; however, despite the administration of large doses and antithrombin III preparations, anticoagulation was insufficient. Therefore, nafamostat mesilate was administered and sufficient anticoagulation was attained. The patient completed surgery under cardiopulmonary bypass, coagulation function was recovered shortly after withdrawal, and no obvious adverse effects were observed.

A small percentage of cases of dermatomyositis are positive for anti-mitochondrial antibodies (AMA), a known marker for primary biliary cirrhosis. AMA-positive myositis is a rare disease that has been reported to be accompanied by myocarditis, resulting in low left ventricular function, supraventricular arrhythmias, and abnormalities of the conduction system. We present a case of AMA-positive myocarditis resulting in sinus arrest during general anesthesia. A 66-year-old female with AMA-positive myocarditis underwent artificial femoral head replacement for osteonecrosis of the femoral head under general anesthesia. During general anesthesia, a nine-second sinus arrest occurred without any inducement. The sinus arrest was thought to be influenced by not only over-suppression caused by severe supraventricular tachycardia derived from sick sinus syndrome but sympathetic depression caused by general anesthesia. Because of the potential for life-threatening cardiovascular events during anesthesia in patients with AMA-positive myositis, it was considered essential to provide adequate preoperative management and intraoperative monitoring during anesthesia for patients with this disease. Herein, we report our case with a literature review.

BACKGROUND Prevention of lethal arrhythmias in congenital long QT syndrome type 1 (LQT1) requires avoidance of sympathoexcitation, drugs that prolong QT, and electrolyte abnormalities. However, it is often difficult to avoid all these risks in the perioperative period of open heart surgery. Herein, we report hypokalemia-induced cardiac arrest in a postoperative cardiac patient with LQT1 on catecholamine. CASE REPORT A 79-year-old woman underwent surgical aortic valve replacement for severe aortic stenosis. Although the initial plan was not to use catecholamine, catecholamine was used in the Postoperative Intensive Care Unit with attention to QT interval and electrolytes due to heart failure caused by postoperative bleeding. Serum potassium levels were controlled above 4.5 mEq/L, and no arrhythmic events occurred. On postoperative day 4, the patient was started on insulin owing to hyperglycemia. Cardiac arrest occurred after the first insulin dose; the implantable cardioverter defibrillator was activated, and the patient's own heartbeat resumed. Subsequent examination revealed that a marked decrease in serum potassium level had occurred after insulin administration. The electrocardiogram showed obvious QT prolongation and ventricular fibrillation following R on T. Thereafter, under strict potassium management, there was no recurrence of cardiac arrest events. CONCLUSIONS A patient with LQT1 who underwent open heart surgery developed ventricular fibrillation after Torsades de Pointes, probably due to hypokalemia after insulin administration in addition to catecholamine. It is important to check serum potassium levels to avoid the onset of Torsades de Pointes in patients with long QT syndrome. In addition, the impact of insulin administration was reaffirmed.

BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is characterized by cardiac depression, respiratory failure, myopathy, and anesthesia for affected patients is challenging. Although several anesthetics have been safely employed, there are no reports on remimazolam used in those patients. CASE PRESENTATION: A 47-year-old male with MELAS syndrome was diagnosed with mitral regurgitation and scheduled for transcatheter mitral valve repair under general anesthesia. Anesthesia was induced with remimazolam and remifentanil (0.3 µg/kg/min). Remimazolam was administered at 12 mg/kg/h until loss of consciousness for approximately 1 min. Anesthesia was maintained with 1.1-1.2 mg/kg/h of remimazolam and 0.1 µg/kg/min of remifentanil without circulatory collapse or severe metabolic acidosis. The tracheal tube was removed in the operating room. CONCLUSION: Remimazolam may be a new option for anesthesia for MELAS syndrome patients with depressed heart function.

BACKGROUND Brugada syndrome is a potentially fatal cardiac arrhythmia characterized by incomplete right bundle-branch block (RBB) and characteristic ST-segment elevation in the anterior electrocardiogram (ECG) leads. This report is of a case of type 2 Brugada syndrome, and discusses the importance of preoperative history and ECG evaluation. CASE REPORT A 32-year-old man was scheduled for tympanoplasty. His preoperative ECG revealed saddleback-type J waves in V₂ (>2 mm) and ST increase (>1 mm) detected 1 week before elective surgery, but the ECG 1 year before showed normal. He had no notable past history. Anesthesia was induced with remifentanil and propofol, and maintained with sevoflurane in combination with remifentanil. Routine monitoring of vital signs was supplemented with V2 monitoring on the ECG. The heart rate was maintained at above 60 beats/min using ephedrine. The course of the operation was uneventful. CONCLUSIONS We managed anesthesia for a patient with a type 2 Brugada syndrome ECG without events, probably because he had no notable past history such as syncope. Type 2 and type 3 Brugada syndrome ECGs are difficult to recognize, and patients with them are considered to be less risky than a patient with a type I ECG. However, as Brugada syndrome ECG is dynamic and changeable, a type 2 or 3 Brugada syndrome ECG can change to a type I ECG under some conditions, and thus should not be overlooked, and the patient's past history or symptoms, such as syncope, should be carefully investigated.

Hyperglycaemia provides a suitable environment for infections and the mechanisms of glucose toxicity include the formation of advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups. Among AGE-associated phenotypes, glycolaldehyde-derived toxic AGE (AGE-3) is involved in the pathogenesis of diabetic complications. Internalisation of endotoxin by various cell types contributes to innate immune responses against bacterial infection. An endotoxin derived from Gram-negative bacteria, lipopolysaccharide (LPS), was reported to enhance its own uptake by RAW264.7 mouse macrophage-like cells, and an LPS binding protein, CD14, was involved in the LPS uptake. The LPS uptake induced the activation of RAW264.7 leading to the production of chemokine CXC motif ligand (CXCL) 10, which promotes T helper cell type 1 responses. Previously, we reported that AGE-3 was internalised into RAW264.7 cells through scavenger receptor-1 Class A. We hypothesized that AGEs uptake interrupt LPS uptake and impair innate immune response to LPS in RAW264.7 cells. In the present study, we found that AGE-3 attenuated CD14 expression, LPS uptake, and CXCL10 production, which was concentration-dependent, whereas LPS did not affect AGE uptake. AGEs were reported to stimulate the receptor for AGEs and Toll-like receptor 4, which cause inflammatory reactions. We found that inhibitors for RAGE, but not Toll-like receptor 4, restored the AGE-induced suppression of CD14 expression, LPS uptake, and CXCL10 production. These results indicate that the receptor for the AGE-initiated pathway partially impairs the immune response in diabetes patients.

WHAT IS KNOWN AND OBJECTIVE: Propofol is the most commonly used intravenous anaesthetic worldwide and is considered to be safe for all ages. However, there have been some reports that propofol induces severe atrioventricular (AV) blocks in humans and some studies demonstrated that propofol suppressed the cardiac conduction system in animals. A precise mechanism by which the block is induced has not been elucidated yet in humans. The objective of this study was to investigate the effects of propofol on the cardiac conduction system and the cardiac autonomic nervous balance in children. METHODS: We enrolled 23 paediatric patients (age: 6-15 years; males: 16, females: 7) who were scheduled to undergo radiofrequency catheter ablation (RFCA) under general anaesthesia. Anaesthesia was induced with 2 mg/kg propofol and 0.5 µg/kg/min remifentanil, and tracheal intubation was performed with the aid of 1 mg/kg rocuronium. Anaesthesia was maintained with 5-7 mg/kg/h propofol and 0.2 µg/kg/min remifentanil during the RFCA. After the completion of the RFCA, anaesthesia was further maintained with 5 mg/kg/h propofol and 0.2 µg/kg/min remifentanil for at least 10 min (LC: low propofol concentration state), followed by the injection of 2 mg/kg propofol and the infusion of 10 mg/kg/h propofol for 10 min (HC: high propofol concentration state). The sinus node recovery time (SNRT), sinoatrial conduction time (SACT), atrial-His (AH) interval and the His-ventricular (HV) interval were measured at the end of both the LC and HC. Cardiac autonomic regulation was simultaneously assessed based on heart rate variability. RESULTS AND DISCUSSION: Propofol significantly suppressed intrinsic cardiac HV conduction, but did not affect the SNRT, SACT or the AH interval. As HV blocks, which occur below the His bundle, are often life-threatening, the HV conduction delay may be a cause of severe AV blocks induced by propofol. Propofol directly suppressed parasympathetic nerve activity, and sympathetic nerve activity was also suppressed. WHAT IS NEW AND CONCLUSION: These results indicate that propofol suppresses the HV conduction and might help to elucidate the mechanism by which propofol causes lethal AV blocks.

BACKGROUND: In a patient with very long-chain acyl-Coenzyme A dehydrogenase (VLCAD) deficiency, metabolism of fatty acids is impaired and a supply of alternative energy is limited when glucose level is insufficient on starvation. CASE PRESENTATION: A 37-year-old woman with VLCAD deficiency was diagnosed with an ovarian cyst and was scheduled for laparoscopic ovarian cystectomy. Glucose was administered intravenously with the start of fasting. Anesthesia was induced with remifentanil, midazolam, and thiamylal, maintained with desflurane and remifentanil. Body temperature was maintained at 36.2-36.7 °C. During anesthesia, hypoglycemia did not occur, creatine kinase levels were in the normal range, and myoglobinuria was not detected. No shivering was observed after extubation. CONCLUSIONS: Glucose was administered to avoid perioperative hypoglycemia. Body temperature was controlled to avoid shivering, which would otherwise increase skeletal muscle energy needs. Blood creatine kinase did not increase, and myoglobinuria was not detected; thus, rhabdomyolysis was unlikely to develop.

BACKGROUND: Severe aortic stenosis (AS) is increasing in the aging society and is a serious condition for anesthetic management. However, approximately one-third of patients with severe AS are asymptomatic. Echocardiography is the most reliable method to detect AS, but it takes time and is costly. METHODS: Data were obtained retrospectively from patients who underwent surgery and preoperative transthoracic echocardiography (TTE). LVH on ECG was determined by voltage criteria (Sv1 + Rv5 or 6 ≥3.5 mV) and/or the strain pattern in V5 and V6. Severe AS was defined as a mean transaortic pressure gradient ≥40 mmHg or aortic valve area ≤1.0 cm2 by TTE. RESULTS: Data for 470 patients aged 28-94 years old were obtained. One hundred and twenty-six patients had severe AS. LVH on ECG by voltage criteria alone was detected in 182 patients, LVH by strain pattern alone was detected in 80 patients and LVH by both was detected in 55 patients. Multivariable logistic analysis revealed that LVH by the strain pattern or voltage criteria, diabetes mellitus, and age were significantly associated with severe AS. The AUC for the ROC curve for LVH by voltage criteria alone was 0.675 and the cut-off value was 3.84 mm V, and the AUC for the ROC for age was 0.675 and the cut-off value was 74 years old. CONCLUSION: Our study suggests that patients who are 74 years old or over with LVH on ECG, especially those with DM, should undergo preoperative TTE in order to detect severe AS.

BACKGROUND Denervation supersensitivity to sympathomimetic drugs has been noted in patients with Parkinson's disease (PD) whose cardiac sympathetic nerves are denervated. This phenomenon is not as well recognized as other complications of PD patients, but anesthesiologists should be aware of it because sympathomimetic drugs can sometimes be dangerous to these patients. CASE REPORT A 60-year-old woman was scheduled for total hip joint replacement under combined spinal-epidural anesthesia and sedation. She had been diagnosed as PD (stage 4 on the Hoehn and Yahr scale) with a history of orthostatic hypotension. Her ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy revealed marked reduction of ¹²³I-MIBG accumulation in the heart. In the operating room, we placed an epidural catheter through the Th12-L1 space, and spinal anesthesia (2.6 mL of 0.5% normobaric bupivacaine) was administered. During the surgery, we infused propofol at 100 mg·hr⁻¹ for sedation. When 4 mg of ephedrine was administered intravenously because of marked decrease in patient's blood pressure, we observed unexpectedly large increases in the systolic blood pressure, from 78 mmHg to 168 mmHg, and the heart rate increased from 52 to 84 beats per minute (bpm). This phenomenon recurred each time 4 mg of ephedrine was administered. CONCLUSIONS We report a case in which ephedrine induced unexpectedly large increases in blood pressure and heart rate in a patient who suffered from PD with severe cardiac sympathetic nerve denervation. We speculate that this phenomenon was caused by denervation supersensitivity of the patient's heart.

BACKGROUND: Parkinson's disease (PD) patients often suffer from cardiac sympathetic denervation, a hallmark of which is orthostatic hypotension. Denervation supersensitivity to sympathomimetic drugs is also seen in such patients, and this phenomenon is important and can be sometimes dangerous. CASE PRESENTATION: A 65-year-old male underwent gastrojejunostomy. The patient had severe PD and did not exhibit metaiodobenzylguanidine (MIBG) accumulation in his heart, which was indicative of cardiac sympathetic nerve denervation. When 8 mg of ephedrine was administered intravenously, an unexpectedly large increase in blood pressure was observed. The phenomenon recurred when 4 mg of ephedrine was administered again, and nicardipine was required to suppress the patient's blood pressure. CONCLUSIONS: Denervation supersensitivity is not as well recognized as other complications seen in PD patients, but anesthesiologists should be aware of it because sympathomimetic drugs can have excessively strong effects in patients with the condition.

糖尿病における免疫機能変化について、糖化最終産物（Advanced Glycation end-products; AGEs）とマクロファージの機能に着目した研究を現在研究調書に記載した計画に基づき遂行中である。本年度までに、研究計画書の１）マクロファージによるLPS取り込み、２）AGEsの作用メカニズムおよび、３）LPS取り込みによる細胞死の機序については予定通り研究が進行した。１）については、マウス単球由来のセルラインである（RAW264.7)を用いたin vitro の研究で、マクロファージはCD14を介してLPSをエンドサイトーシスにより取り込むことを確認した。そして、CD14以外の主要なLPSやAGEsに関与すると報告のある受容体（TLR ファミリー、スカベンジャー受容体、RAGE等）についても検討を行い、それらがマクロファージのLPS取り込みに影響を与えていないことも確認した。さらに、LPSを取り込んだマクロファージはCXCL10等のインターフェロンを産生し、免疫細胞の誘導に関与することが確認された。2)に関しては、AGEsの中で特に生理活性が高く糖尿病の病因の１つとして考えられているグリコールアルデヒド由来のAGEであるAGE3を用いた研究を行った。この研究により、AGE3はマクロファージによるLPS取り込みを抑制することが発見された。AGE3のLPS取り込み抑制のメカニズムは未だ完全には確認できていないが、種々の検討によりRAGEが関与してい ることは明らかとなった。これまでの成果は学術論文としてPLOS ONEに掲載された。現在、モデルマウスを用いた実験系の確立に取り組んでいる。また、in vitro実験の副産物として、AGE3が内皮細胞の血管新生を促進する可能性があることが明らかになった。そのため、こちらについてもヒト内皮細胞を用いたin vitroでの新たに実験系を構築し、検討を進めている。

In diabetic patients, perioperative blood glucose control does not provide a sufficient postoperative prognosis improving effect. Therefore, we think that an approach to chronic etiology is necessary, and it is attracting attention as a cause of diabetic complications, but we focus on advanced glycation end-product (AGEs) whose mechanism of action has not been fully elucidated. did. Based on the results of our previous studies, we hypothesized that AGEs inhibit M2 polarization of macrophages, prolong wound healing mechanism, and induce postoperative organ damage.