Lactic acid induces HSPA1A expression through ERK1/2 activation.

Heat shock protein (HSP) A1A protects cells from various stressors. The concentrated liquid of the traditional Japanese rice black vinegar Kurozu increased HSPA1A expression in normal rat liver RLN-10 cells. Lactic acid, the primary component of concentrated Kurozu, induced HSPA1A expression in a concentration-dependent manner. Induction with 4 m m lactic acid increased HSPA1A expression by three times compared with that in the absence of lactic acid. The induction was inhibited by staurosporine or a selective MEK1/2 inhibitor (SL327). The phosphorylation of ERK1/2 was increased by lactic acid. These results suggest that lactic acid induces HSPA1A expression by activating ERK1/2. As well as lactate, 3,5-dihydroxybenzoic acid (DHBA), a ligand for G protein-coupled receptor 81 (GPR81), also induced HSPA1A at lower concentrations than lactate. The increased effect of DHBA on HSPA1A expression as compared with lactate may be related to the higher affinity of DHBA for GPR81 than of lactate.

Atrial tachycardia with multiple reconductions across the surgical incision.

Incisional atrial tachycardia (AT) with multiple penetrating points on one surgical incision has not been reported yet. We present a case of incisional AT following mitral valve annuloplasty with a superior transseptal approach, in which two reconduction sites were parts of the reentrant circuit. Radiofrequency ablation at the reconduction site successfully terminated the tachycardia. A total of four penetrating points were found on the incision line, and radiofrequency ablation at these sites was completed. Detailed mapping of possible reconduction sites along the incision line should be performed to avoid further instances of AT following open heart surgery.

2.8-Å crystal structure of Escherichia coli YidC revealing all core regions, including flexible C2 loop.

YidC/Alb3/Oxa1 family proteins are involved in the insertion and assembly of membrane proteins. The core five transmembrane regions of YidC, which are conserved in the protein family, form a positively charged cavity open to the cytoplasmic side. The cavity plays an important role in membrane protein insertion. In all reported structural studies of YidC, the second cytoplasmic loop (C2 loop) was disordered, limiting the understanding of its role. Here, we determined the crystal structure of YidC including the C2 loop at 2.8 Šresolution with R/Rfree = 21.8/27.5. This structure and subsequent molecular dynamics simulation indicated that the intrinsic flexible C2 loop covered the positively charged cavity. This crystal structure provides the coordinates of the complete core region including the C2 loop, which is valuable for further analyses of YidC.

Right ventricular scar-related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics, mapping, and ablation of underlying heart disease.

BACKGROUND: Right ventricular (RV)-scar related ventricular tachycardia (VT) is often due to arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) or cardiac sarcoidosis (CS), but some patients whose clinical course has not been described do not fulfill diagnostic criteria for these diseases. We sought to characterize the electrophysiologic substrate and catheter ablation outcomes of such patients, termed RV cardiomyopathy of unknown source (RCUS). METHODS AND RESULTS: Data of 100 consecutive patients who presented with RV cardiomyopathy and/or RV-related VT for ablation were reviewed (51 ARVC/D, 22 CS; 27 RCUS). Compared to ARVC/D, RCUS patients were older (P = 0.001), less commonly had RV dilatation (P = 0.001) or dysfunction (P = 0.01) and fragmented QRS, parietal block, and T-wave inversion. Compared to CS, R-CUS patients had less severe LV dysfunction. Extent and distribution of endocardial/epicardial scar and inducible VTs in RCUS patients were comparable with ARVC/D and CS patients. At a median follow-up of 23 months, RCUS patients had more favorable VT-free survival (RCUS 71%, ARVC/D 60%, CS 41%, P = 0.03) and survival free of death or cardiac transplant (RCUS 92%, ARVC/D 92%, CS 62%, P = 0.01). No RCUS patients developed new criteria for ARVC/D or CS in follow-up. CONCLUSIONS: Up to one-third of patients with RV scar-related VT are not classifiable as ARVC/D or CS. These patients had a somewhat better prognosis than ARVC/D or sarcoid and did not develop evidence of these diseases during the initial 2 years of follow-up. The extent to which this population comprises mild ARVC/D, CS, or other diseases is not clear.

Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the Assessment of Myocardial Ischemia.

BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

Catheter Ablation of Atypical Atrioventricular Nodal Reentrant Tachycardia.

BACKGROUND: Because of its low prevalence, data on atypical atrioventricular nodal reentrant tachycardia (AVNRT) are scarce, and the optimal ablation method has not been established. Our study aimed at assessing the efficacy and safety of conventional slow pathway ablation, as applied for typical cases, in atypical AVNRT. METHODS: We studied 2079 patients with AVNRT subjected to slow pathway ablation. In 113 patients, mean age 48.5±18.1 years, 68 female, atypical AVNRT or coexistent atypical and typical AVNRT without other concomitant arrhythmia was diagnosed. Ablation data and outcomes were compared with a group of age- and sex-matched control patients with typical AVNRT. RESULTS: Fluoroscopy and radiofrequency current delivery times were not different in the atypical and typical groups, 20.3±12.2 versus 20.8±12.9 minutes (P=0.730) and 5.9±5.0 versus 5.5±4.5 minutes (P=0.650), respectively. Slow pathway ablation was accomplished from the right septum in 110 patients, and from the left septum in 3 patients, in the atypical group. There was no need for additional ablation lesions at other anatomic sites, and no cases of atrioventricular block were encountered. Recurrence rates of the arrhythmia were 5.6% in the atypical (6/108 patients) and 1.8% in the typical (2/111 patients) groups in the next 3 months following ablation (P=0.167). CONCLUSIONS: Conventional ablation at the anatomic area of the slow pathway is the therapy of choice for symptomatic AVNRT, regardless of whether the typical or atypical form is present.

A Comparison of Women and Men Undergoing Catheter Ablation for Sustained Monomorphic Ventricular Tachycardia.

INTRODUCTION: Women are underrepresented in clinical studies on catheter ablation (CA) for ventricular tachycardia (VT). The role of gender as a predictor for VT recurrence after CA is unclear and complication rates have not been compared in a large cohort. METHODS AND RESULTS: We analyzed data of consecutive patients undergoing CA for sustained monomorphic VT at our center between 2005 and 2015. A total of 948 patients underwent 1314 ablation procedures: 114 patients without structural heart disease (SHD) (48% female), 486 with coronary artery disease (CAD) (9% female), 301 with nonischemic cardiomyopathy (NICM) (22% female), and 46 with arrhythmogenic right ventricular cardiomyopathy (ARVC) (17% female). Women with CAD and NICM were younger than men at first ablation (63 years vs. 68 years, P = 0.05; resp. 53 years vs. 59 years, P = 0.026) with no other significant differences in baseline characteristics. Age, LVEF, NYHA-class, and VT-recurrence but not gender were independently associated with increased mortality in CAD and NICM. Mortality rates in patients with no SHD and ARVC are low in men (0%, 2.6%) and women (1.8%, 0%). CONCLUSIONS: Although heart disease tends to present later in women, our data do not suggest that women are referred later than men. Women with CAD or NICM and VT present for ablation at younger age with disease severity comparable to men. VT ablation in women can be accomplished with success- and complication rates comparable to male patients in both those with and without SHD.

Beyond the Storm: Comparison of Clinical Factors, Arrhythmogenic Substrate, and Catheter Ablation Outcomes in Structural Heart Disease Patients With versus Those Without a History of Ventricular Tachycardia Storm.

AIMS: Catheter ablation can be lifesaving in ventricular tachycardia (VT) storm, but the underlying substrate in patients with storm is not well characterized. We sought to compare the clinical factors, substrate, and outcomes differences in patients with sustained monomorphic VT who present for catheter ablation with VT storm versus those with a nonstorm presentation. METHODS: Consecutive ischemic (ICM; n = 554) or nonischemic cardiomyopathy patients (NICM; n = 369) with a storm versus nonstorm presentation were studied (ICM storm 186; NICM storm 101). RESULTS: In ICM, storm compared with nonstorm patients had significantly lower left ventricular (LV) ejection fraction (EF), greater number of antiarrhythmic drug (AAD) failures, slower VTs, greater number of scarred LV segments, higher incidence of anterior, septal, and apical endocardial LV scar (all P < 0.05). However, outcomes in follow-up were similar (12-month ventricular arrhythmia [VA]-free survival: 51% vs. 52%, P = 0.6; survival free of death/transplant 75% vs. 87%, P = 0.7). In addition to the above differences, NICM storm patients were also older; however, the extent and distribution of scar was similar except for a higher incidence of lateral endocardial scar in storm patients (P = 0.05). VA-free survival (36% vs. 47%, P = 0.004) and survival free of death/transplant, however, were worse in NICM storm than nonstorm patients (72% vs. 88%, P = 0.001). NICM storm patients had worse VA-free survival than ICM storm patients. CONCLUSION: There are differences in clinical factors and scar patterns in patients undergoing VT ablation who present with VT storm versus those with a nonstorm presentation. Clinical outcomes are worse in NICM storm patients.

Substrate-Based Ablation Versus Ablation Guided by Activation and Entrainment Mapping for Ventricular Tachycardia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Substrate-based ablation for scar-related ventricular tachycardia (VT) has gained prominence: however, there is limited data comparing it to ablation guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs. We compared the acute procedural efficacy and outcomes of predominantly substrate-based ablation versus ablation guided predominantly by activation and entrainment mapping. METHODS AND RESULTS: Database searches through April 2016 identified 6 eligible studies (enrolling 403 patients, with 1 randomized study) comparing the 2 strategies. The relative risk of VT recurrence at follow-up was assessed as the primary outcome using a random-effects meta-analysis. Secondary endpoints of acute success (based on noninducibility of VT), procedural complications, and mortality were assessed using weighted mean difference with the random effects model. At a median follow-up of 18 months, the relative risk (RR) of VT recurrence was not significantly different with substrate-based versus activation/entrainment guided VT ablation (0.72, 95% confidence interval [CI] 0.44-1.18), P = 0.2). Acute success (RR 1.02, 95% CI 0.95-1.1, P = 0.6), procedural complications (RR 0.8, 95% CI 0.35-1.82, P = 0.5) cardiovascular mortality and total mortality did not differ significantly (RR 0.83, 95% CI 0.38-1.79, P = 0.6 and RR 0.76, 95% CI 0.36-1.59, P = 0.5, respectively). CONCLUSIONS: This meta-analysis demonstrates similar acute procedural efficacy, and complications, VT recurrence and mortality rates when comparing a predominantly substrate-based ablation strategy to a strategy guided predominantly by activation and entrainment mapping of inducible and hemodynamically tolerated VTs.

Clinical Significance of Peripheral Endothelial Function for Left Atrial Blood Stagnation in Nonvalvular Atrial Fibrillation Patients With Low-to-Intermediate Stroke Risk.

BACKGROUND: In patients who have atrial fibrillation (AF) with CHADS2score of 0-1 (categorized as low-to-intermediate risk), there is little information on stratifying the risk of stroke. This study aimed to determine whether impaired endothelial function assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) predicted left atrial blood stagnation in these patients. METHODS AND RESULTS: We enrolled 81 consecutive patients with nonvalvular AF. The reactive hyperemia index (RHI) was measured using RH-PAT. Transesophageal echocardiography was performed to determine spontaneous echo contrast (SEC) before direct-current cardioversion or radiofrequency catheter ablation. SEC was found in 49 patients (60%). The RHI was significantly lower in patients with than without SEC. Multivariate analysis demonstrated that RHI was one of the independent determinants of SEC (OR per 0.1, 1.26; 95% CI, 1.11-1.49; P=0.002) in all patients. In addition, RHI was a significant determinant of SEC (AUC, 0.73; 95% CI, 0.63-0.89; P=0.0017) in patients with low-to-intermediate risk. At an RHI cut-off <1.62, the sensitivity and specificity for the identification of patients with SEC were 58% and 89%, respectively. CONCLUSIONS: Impaired endothelial function assessed by RH-PAT might help to predict the presence of SEC in patients with low-to-intermediate risk of stroke. (Circ J 2016; 80: 2117-2123).

Clinical Utility of Atrial Electromechanical Conduction Time Measured with Speckle Tracking Echocardiography after Catheter Ablation in Patients with Atrial Fibrillation: A Validation Study with Electroanatomical Mapping.

PURPOSE: Our recent report demonstrated that atrial electromechanical conduction time (EMT-ε) measured with speckle tracking echocardiography could predict cardiac events in patients with pathological left ventricular hypertrophy. This study aimed to validate EMT-ε by comparison with electroanatomical mapping and to investigate the clinical utility of EMT-ε in patients with atrial fibrillation (AF) undergoing catheter ablation. METHODS: Forty-six patients with preserved LV ejection fraction (LVEF ≥ 50%) undergoing pulmonary vein isolation (PVI) for AF were studied. Atrial electrical conduction delay was determined by measuring atrial electrical activation time (EAT) using three-dimensional electroanatomical mapping just after PVI. Echocardiographic parameters were acquired within 24 hours and at 6 months after PVI. The study also included 10 control subjects. RESULTS: AF patients had a larger left atrial (LA) volume index (LAVI) and more prolonged EMT-ε compared with control subjects. According to the validation study, EAT was closely related to EMT-ε and a', and this association was independent of LAVI and the presence of persistent AF (EMT-ε: R(2) = 0.342, P < 0.0001, a': R(2) = 0.337, P < 0.0001). At 6 months after PVI, LAVI and EMT-ε were significantly improved. During continued follow-up beyond 6 months (total follow-up, 26 ± 12 months), the EMT-ε shortening at 6 months after PVI was significantly greater in AF-free patients than patients with AF recurrence. CONCLUSIONS: This study suggested that the EMT-ε could be a useful echocardiographic marker of LA electromechanical abnormalities in patients with AF.

[Intraoperative Aortic Dissection].

A 69-year-old man underwent mitral valve replacement for suspected infective endocarditis and coronary artery bypass grafting with left internal thoracic artery and saphenous vein graft. During the period of coming off cardiopulmonary bypass, enlargement of the ascending aorta and bleeding from the suture line were observed. Intraoperative transesophageal echocardiography and direct epi-aortic echography revealed acute aortic dissection extending from the ascending aorta to the descending aorta. Replacement of the ascending aorta was performed under deep hypothermic circulatory arrest and continuous retrograde cerebral perfusion through the superior vena cava. The postoperative course was uneventful and he was discharged on postoperative day 41. Aortic dissection during cardiac operation is a rare but serious complication. Prompt recognition and appropriate surgical management are necessary to improve patient outcome.

Excimer emission properties on pyrene-labeled protein surface: correlation between emission spectra, ring stacking modes, and flexibilities of pyrene probes.

The excimer emission of pyrene is popularly employed for investigating the association between pyrene-labeled biomolecules or between pyrene-labeled places in a biomolecule. The property of pyrene excimer emission is affected by the fluctuation in ring stacking modes, which originates from the structural flexibilities of pyrene probes and/or of labeled places. Investigations of the excimer emission in terms of dynamics of pyrene stacking modes provide the detailed spatial information between pyrene-labeled places. In order to evaluate the effects of probe structures and fluctuation in pyrene-pyrene association modes on their emission properties on protein surface, three types of pyrene probe with different linker lengths were synthesized and conjugated to two cysteine residues in the A55C/C77S/V169C mutant of adenylate kinase (Adk), an enzyme that shows a structural transition between OPEN and CLOSED forms. In the CLOSED form of Adk labeled by a pyrene probe with a short linker, excimer emission was found to be predominated by the ground-state association of pyrenes. The pyrene stacking structure on the protein surface was successfully determined by an X-ray crystallographic analysis. However, the emission decay in the protein suggested the existence of several stacking orientations in solution. With the increase in the linker length, the effect of fluctuation in pyrene association modes on the spectral properties distinctly emerged at both ground and excited states. The combination of steady-state and time-resolved spectroscopic analyses is useful for differentiation in the origin of the excimer emission, which is essential for precisely understanding the interaction fashions between pyrene-labeled biomolecules.

Characteristics of Left Atrial Deformation Parameters and Their Prognostic Impact in Patients with Pathological Left Ventricular Hypertrophy: Analysis by Speckle Tracking Echocardiography.

BACKGROUND: The pathological process of left ventricular (LV) hypertrophy is associated with left atrial (LA) remodeling. This study was aimed to evaluate the prognostic value of LA strain parameters in patients with pathological LV hypertrophy. METHODS: This study included 95 patients with hypertensive heart disease (HHD: n = 24), hypertrophic cardiomyopathy (HCM: n = 56), cardiac amyloidosis (CA: n = 15), and control subjects (n = 20). We used two-dimensional speckle tracking echocardiography (STE) to analyze LA global strain. LA electromechanical conduction time (EMT) at the septal (EMT-septal) and lateral wall (EMT-lateral), and their time difference (EMT-diff) were calculated. The incidence of cardiac death and heart failure hospitalization was defined as major cardiac events and that of atrial fibrillation as secondary outcome. RESULTS: Left atrial volume index was increased and LA booster strain was decreased in the HCM and CA groups compared with the HHD group. EMT-lateral was increased in the diseased groups compared with the control. EMT-diff was prolonged in the CA group compared with the HCM group. During the follow-up period (mean 3.4 years), major cardiac events and atrial fibrillation occurred in 17 and 13 patients, respectively. The occurrence of atrial fibrillation was associated with CA etiology, E/e', LA volume index, LAa, and EMT-lateral. The incidence of major cardiac events was independently correlated with LA volume index and EMT-diff in multivariate analysis. CONCLUSION: This study suggested that the EMT-diff could discriminate patients with a high risk of cardiac events among patients with pathological LV hypertrophy.

[Mitral valve replacement after previous coronary artery bypass grafting with functioning left internal thoracic artery graft: effectiveness of the method using a direct vision retrosternal approach; report of a case].

Performing a redo-sternotomy when a mammary artery graft is patent can be rather difficult. We previously reported a redo-sternotomy technique involving direct visualization with a retrosternal dissection (DR) method using a Kent's retractor. The DR method in detail is as follows: 1) A midline skin incision is extended to the abdomen about 5 cm. 2) The bilateral costal arches are divided from the rectal muscle. 3). A pair of retractors is placed under the costal arch. 4) A stainless steel wire is applied to the previous sternal wire at the center of the sternum. 5) The retractor and sternal wire are lifted up using the Kent's retractor to widen the retrosternal space. 6) The sternum and sub-sternal tissue are carefully divided using an electronic scalpel or metal retractor with an entirely sternal length. 7) Routine sternotomy is performed using a Stryker. Herein, we report a patient who had undergone cardiac surgery, coronary artery bypass grafting (CABG), using a left internal mammary artery and mitral annuloplasty 2 years previously, and then developed mitral regurgitation caused by infectious endocarditis. He successfully underwent redo-sternotomy and mitral valve replacement using the DR method. In a patient with a patent internal mammary artery, the DR method greatly reduces the risk of graft injury.

Flavor assessment of a lactic fermented vinegar described in Japanese books from the Edo period (1603-1867).

Aims: Rice vinegar is a traditional fermented seasoning in Japan, and its production remained unchanged for over 800 years until the Edo period. However, based on the available information regarding rice vinegar production methods from this period and the results of reproduction experiments, we speculated that unlike the modern-day acetic fermented vinegar, rice vinegar produced during the Edo period was lactic fermented. Main methods: To verify this assumption, we analyzed the flavor components of Honcho, a lactic fermented product prepared using a method described in books, including "Honchoshokkan" from the Edo period, by capillary electrophoresis/time-of-flight mass spectrometry, high-performance liquid chromatography, gas chromatography mass spectrometry, and taste sensor analysis. Sensory evaluation was also conducted to assess validation as a seasoning. Results: Honcho contains 2 % lactic acid, which gives it its acidity, and small amounts of other nonvolatile acids, but significantly lower levels of acetic acid (0.188 ± 0.015 g/100 mL, p < 0.01). It contains more than double the free amino acids of Kurozu, a modern rice vinegar, and more glutamic acid. Boiling to remove ethanol from yeast fermentation concentrated the free amino acids 1.5 times. Sensor taste analysis showed Honcho had weaker acidity but stronger umami taste than commercial rice vinegar. The volatile compounds related to acetic acid fermentation were significantly different between Honcho and Kurozu. Boiling increased Honcho's acidity, mainly through non-volatile acids. Significance: These findings provide evidence to indicate that Honcho was an acidic seasoning for heat-cooking, which is uncommon in Japanese cuisine today and is mentioned in Edo period books. This seasoning contains many amino acids, implying that it adds umami flavor, not only the sourness of modern vinegar.

Characterization of the membrane vesicle fraction from Acetobacter sp. WSS15.

A bacterium that produces membrane vesicles (MVs), strain WSS15, was isolated from a traditional vinegar in Japan called Kurozu. A phylogenetic analysis of 16S rRNA gene sequences indicated that this bacterium belongs to the genus Acetobacter. MVs and peptidoglycan-associated lipoprotein (Pal) were detected in the MV fraction of strain WSS15. In the presence of the WSS15 MV fraction, murine macrophages produced the pro-inflammatory cytokine interleukin-6 (IL-6) via the recognition by superficial Toll-like receptor 2 (TLR2). WSS15 MVs adhered to the cell surface of macrophages. The macrophages secreted IL-6 through the TLR2 recognition of an acylated N-terminal peptide of Pal. We elucidated the mode of action of WSS15 MVs on immune cells and identified the Pal peptide from strain WSS15 as an agonist of TLR2.

Development of a two-dimensional LC-MS/MS system for the determination of proline and 4-hydroxyproline enantiomers in biological and food samples.

A two-dimensional LC-MS/MS system has been developed for the enantioselective determination of proline (Pro), cis-4-hydroxyproline (cis-4-Hyp) and trans-4-hydroxyproline (trans-4-Hyp) in a variety of biological samples. The amino acids were pre-column derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and the NBD-derivatives were separated by a reversed-phase column (Singularity RP18) as their D plus L mixtures in the first dimension. The collected target fractions were then introduced into the second dimension where the enantiomers were separated by a Pirkle-type enantioselective column (Singularity CSP-001S) and determined by a tandem mass spectrometer (Triple Quad™ 5500). The method was validated by the standard amino acids and also by human plasma, and sufficient results were obtained for the calibration, precision and accuracy. The method was applied to human plasma and urine, bivalve tissues and fermented food/beverages. D-Pro was widely found in the human physiological fluids, bivalves and several fermented products. Although trans-4-D-Hyp was not found in all the tested samples, cis-4-D-Hyp was present in human urine and tissues of the ark shell, and further studies focusing on the origin and physiological significance of these D-enantiomers are expected.

Reversible switching of fluorophore property based on intrinsic conformational transition of adenylate kinase during its catalytic cycle.

Adenylate kinase shows a conformational transition (OPEN and CLOSED forms) during substrate binding and product release to mediate the phosphoryl transfer between ADP and ATP/AMP. The protein motional characteristics will be useful to construct switching systems of fluorophore properties caused by the catalytic cycle of the enzyme. This paper demonstrates in situ reversible switching of a fluorophore property driven by the conformational transition of the enzyme. The pyrene-conjugated mutant adenylate kinase is able to switch the monomer/excimer emission property of pyrene on addition of ADP or P(1)P(5)-di(adenosine-5')pentaphosphate (Ap5A, a transition state analog). The observation under the dilute condition (~0.1 µM) indicates that the emission spectral change was caused by the motion of a protein molecule and not led by protein-protein interactions through π-π stacking of pyrene rings. The switching can be reversibly conducted by using hexokinase-coupling reaction. The fashion of the changes in emission intensities at various ligand concentrations is different between ADP, Mg(2+)-bound ADP, and Mg(2+)-bound Ap5A. The emission property switching is repeatable by a sequential addition of a substrate in a one-pot process. It is proposed that the property of a synthetic molecule on the enzyme surface is switchable in response to the catalytic cycle of adenylate kinase.

Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases.

INTRODUCTION: This study aimed to elucidate the clinical characteristics and management of periesophageal vagal nerve injury complicating the ablation of atrial fibrillation (AF). METHODS AND RESULTS: A total of 3,695 patients with drug-resistant AF underwent extensive pulmonary vein isolation at our institution. Either a nonirrigated or an irrigated ablation catheter was employed, with radiofrequency power of 25-40 W. Esophageal temperature was monitored in 3,538 patients: when the esophageal temperature reached 42°C radiofrequency delivery was stopped. A total of 11 patients (60 ± 11 years, 10 males) were diagnosed as having a periesophageal vagal nerve injury after the AF ablation. Symptoms included nausea, vomiting, bloating, constipation, and gastric pain, which occurred within 72 hours after the procedure. Gastrointestinal fluoroscopy and/or endoscopy revealed gastric hypomotility (10 patients) and pyloric spasm (1 patient). Intravenous erythromycin (3 mg/kg every 8 hours) was effective in relieving symptoms in 5 patients, and the patient with pyloric spasm underwent esophagojejunal anstomosis. Eight patients almost fully recovered within 40 days; however, 3 patients suffered from severe symptoms for 3-12 months. This complication occurred in 4 of the 157 patients (2.5%) who did not have esophageal temperature monitoring, and 7 of the 3,538 (0.2%) who did (P = 0.0007). The 3 patients with persistent severe symptoms received no esophageal temperature monitoring. CONCLUSION: The clinical course and severity of the periesophageal vagal nerve injury varied, but most patients finally recovered with conservative treatment. Radiofrequency delivery under esophageal temperature monitoring might reduce both the incidence and the severity of this complication.