小林 欣夫

Sodium-ion batteries are attractive energy storage media owing to the abundance of sodium, but the low capacities of available cathode materials make them impractical. Sodium-excess metal oxides Na2MO3 (M: transition metal) are appealing cathode materials that may realize large capacities through additional oxygen redox reaction. However, the general strategies for enhancing the capacity of Na2MO3 are poorly established. Here using two polymorphs of Na2RuO3, we demonstrate the critical role of honeycomb-type cation ordering in Na2MO3. Ordered Na2RuO3 with honeycomb-ordered [Na1/3Ru2/3]O-2 slabs delivers a capacity of 180 mAhg(-1) (1.3-electron reaction), whereas disordered Na2RuO3 only delivers 135 mAhg(-1) (1.0-electron reaction). We clarify that the large extra capacity of ordered Na2RuO3 is enabled by a spontaneously ordered intermediate Na1RuO3 phase with ilmenite O1 structure, which induces frontier orbital reorganization to trigger the oxygen redox reaction, unveiling a general requisite for the stable oxygen redox reaction in high-capacity Na2MO3 cathodes.

Background: Endothelial dysfunction after drug-eluting stent implantation has been demonstrated. It may be associated with adverse cardiovascular events during follow-up. Olmesartan, an angiotensin II receptor antagonist, ameliorates endothelial dysfunction. The present study evaluated the protective effect of olmesartan on endothelial function after everolimus-eluting stent (EES) implantation. Methods: A total of 40 patients who underwent EES implantation were randomly assigned to the olmesartan group (20 patients with 30 lesions) or the non-olmesartan group (20 patients with 32 lesions). Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15 mm proximal and distal to EES in response to intracoronary infusion of acetylcholine (Ach; 10(-8) and 10(-7) mol/L) at 9-month follow-up. Endothelium-independent vasomotion was assessed after an intracoronary bolus of isosorbide dinitrate. Results: In both groups, Ach infusion did not induce significant vasoconstriction in the segment either proximal or distal to the EES. The changes in coronary diameter in response to 10(-8) mol/L (-2.0 +/- 4.4% vs. -0.6 4.1%, p = 0.33) and 10(-7) mol/L. (-1.8 +/- 7.9% vs. -0.3 +/- 7.6%, p = 0.57) Ach infusion in the segment proximal to EES were not significantly different between the olmesartan group and the non-olmesartan group. There were no significant differences in vasoconstriction in response to 10(-8) mol/L (-0.8 +/- 5.8% vs. -0.9 +/- 7.0%, p = 0.96) and 10(-7) mol/L (1.8 +/- 9.7% vs. -1.8 +/- 9.7%, p = 0.16) Ach infusion in the segment distal to EES between the 2 groups. Endothelium-independent vasodilation after nitrate infusion did not differ between the 2 groups. Conclusions: Endothelial dysfunction is not observed after EES implantation. Olmesartan does not improve endothelial function after EES implantation. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Aims: Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to have protective effects on various cells but it is unclear how DPP-4 inhibitors have cardioprotective effects. Our aim was to study the mechanisms of cardioprotective effects by DPP-4 inhibition. Methods and results: C57BL/6 mice and DPP-4 knockout (DPP-4K0) mice were subjected to left coronary artery ligation to produce acute myocardial infarction (MI). C57BL/6 mice were then treated with vehicle or DPP-4 inhibitor. Left ventricular function, infarct size, the number of vessels, and myocardial ischemia were assessed at 5 days after MI. The treatment with DPP-4 inhibitor significantly improved cardiac function and decreased the infarct size. DPP-4 inhibitor increased the ratio of endothelial cell numbers to a cardiomyocyte. The extent of myocardial ischemia and the number of TUNEL-positive cells in the border area were significantly decreased by DPP-4 inhibitor. Stromal cell-derived factor-1 alpha (SDF-1 alpha) level in myocardium was significantly increased by DPP-4 inhibitor. Those cardioprotective effects after MI were also recognized in DPP-4K0 mice. DPP-4 protein was expressed on rat neonatal cardiomyocytes and DPP-4 inhibitor significantly reduced hypoxia-induced apoptosis in the cardiomyocytes. However, this effect was abolished by the pretreatment with a CXCR4 antagonist or a signal transducer and activator of transcription 3 (STAT3) inhibitor. The beneficial effects of DPP-4 inhibitor on heart failure after MI were abolished by cardiomyocyte-specific deletion of STAT3. Conclusions: DPP-4 inhibition may have direct protective effects on the post-MI heart by inducing an antiapoptotic effect and inhibiting a decrease in vessel number through the SDF-1 alpha/CXCR4-mediated STAT3 signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.

Background: Coronary artery drug eluting stents coated with polymer which contained immunosuppressant or anticancer drug. Such drugs eluted within several months to prevent stent restenosis. Damage of polymer of first and second generation drug eluting stents during percutaneous coronary intervention (PCI) were reported previously[1,2]. However, damage of polymer of third generation drug eluting stents during PCI were unknown. … Methods and results: A man with severely calcified 90% stenosis in the left anterior descending coronary artery (LAD) underwent PCI. After predilatation with balloon catheters, a third generation platinum chromium everolimus-eluting stent which coated abluminal bioabsorbable polymer (SYNERGY, Boston Scientific) was tried to advance in the LAD. However, it failed to deliver to the target lesion due to severe cartification. The delivery failure stent was scanned by electron microscopy. Damage to the bioabsorbable polymer of the platinum chromium everolimus-eluting stent was delamination of abluminal polymer (Fig. 1) Compared to the first and second generation drug eluting stents, damege to polymer of third generation drug eluting stent may occur easily and severely when it is delivered through a calcified coronary artery.

Introduction: Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. Methods and analysis: This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. Ethics and dissemination: The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals.

BACKGROUND: Pulmonary vein isolation (PVI) has become an important option for treating patients with atrial fibrillation (AF). Periesophageal nerve (PEN) injury after PVI causes pyloric spasms and gastric hypomotility. This study aimed to clarify the impact of PVI on gastric motility and assess the prevalence of gastric hypomotility after PVI. METHODS: Thirty consecutive patients with AF underwent PVI under luminal esophageal temperature (LET) monitoring. The (13)C-acetate breath test was conducted before and after the procedure for all patients (PVI group). Gastric emptying was evaluated using the time to peak concentration of (13)CO2 (T max). This test was also conducted in another 20 patients who underwent catheter ablation procedures other than PVI (control group). RESULTS: The number of patients with abnormal T max (≥75 min) increased from seven (23%) to 13 (43%) and from three (15%) to five (25%) after the procedure in the PVI group and control group, respectively. The mean T max was longer after PVI than before PVI (64±14 min vs. 57±15 min, p=0.006), whereas there was no significant difference before and after the procedure in the control group. However, no significant difference in ΔT max was observed between the two groups (p=0.27). No patients suffered from symptomatic gastric hypomotility. CONCLUSIONS: Asymptomatic gastric hypomotility occurred more often after PVI. However, the average impact of PVI on gastric motility was minimal.

Purpose: We evaluated the consistency of different-assessors in estimating three-dimensional (3D) global-longitudinal-strain (GLS) of left (LV) and right ventricle (RV) using transthoracic-echocardiography (TTE) for LV and RV systolic-function. We compared results from two-independent-specialists using this-approach for 3D LV and RV parameters in a population with 74% hypertrophic-cardiomyopathy (HCM) patients. Methods: 58 patients (43 HCM(32 male; 62 +/- 15 years) and 15 controls (5 male; 53 +/- 22 years)) underwent TTE (Vivid-E9) to measure 2D and 3D GLS of the LV and RV by two-independent-specialists. Results: Consistencies of estimates of 3D LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection-fraction (EF) between the two-assessors were 0.872 (3D LVEDV, P < 0.001), 0.797 (3D LVESV, P < 0.001), and 0.215 (3D LVEF, P = 0.105). Consistencies of 2D and 3D LV GLS between two-assessors were 0.900 (2D LVGLS, P < 0.001) and 0.874 (3D LVGLS, P < 0.001). Consistencies of estimates of 3D RVEDV, RVESV, and RVEF between two assessors were 0.781 (3D RVEDV, P < 0.001), 0.755 (3D RVESV, P < 0.001), and 0.26 (3D RVEF, P = 0.049). Consistencies of 2D and 3D GLS of whole RV and those of RV free wall only between two-assessors were 0.886 (2D GLS of whole RV, P < 0.001), 0.687 (3D GLS of whole RV, P < 0.001), 0.707 (2D GLS of RV free wall, P < 0.001), and 0.630 (3D GLS of RV free wall, P < 0.001). Conclusions: Consistencies of independent-estimates of 3D GLS of the LV and RV using TTE between two-assessors were worse than for 2D GLS of the LV and RV, but better than for 3D LVEF and RVEF in a population with 74% HCM patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Background: The pharmacodynamic effects of changing from standard-dose clopidogrel to low-dose (3.75 mg) prasugrel in Japanese patients are largely unknown. Methods and Results: A total of 53 consecutive Japanese patients with stable coronary artery disease (CAD) who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75 mg prasugrel. At day 14, prasugrel was switched to 75 mg clopidogrel. Platelet reactivity was measured using the Verify Now assay at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as high on-treatment platelet reactivity (HPR). The prevalence of HPR (18.9% vs. 41.5% vs. 44.2%, P<0.001) and the PRU level (154.3 +/- 54.2 vs. 196.2 +/- 55.5 vs. 194.6 +/- 55.8, P<0.001) were significantly lower on prasugrel maintenance therapy compared with the clopidogrel therapy before and after switching. The CYP2C19 genotypes that account for the 3 phenotypes (ie, extensive metabolizer, intermediate metabolizer, and poor metabolizer) had a significant impact on platelet reactivity with clopidogrel (174.9 +/- 54.0 vs. 193.1 +/- 56.5 vs. 240.6 +/- 25.4 PRU, P<0.001) but not prasugrel (147.0 +/- 51.9 vs. 147.5 +/- 58.3 vs. 184.4 +/- 38.3 PRU, P=0.15). Conclusions: Low-dose prasugrel achieves stronger platelet inhibition than clopidogrel in Japanese patients with stable CAD.

Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the pathogenesis of the relation between SUA level and coronary plaque characteristics has not been fully evaluated. The aim of this study was to investigate the relation between SUA level and plaque composition of nonculprit lesions in patients with ACS. A total of 81 patients with ACS who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were included. They were classified into 3 groups according to tertiles of SUA level. Using integrated backscatter (IB) -IVUS system, tissue components were classified into 4 categories: calcium deposits, dense fibrosis, fibrosis, and lipid. Tertiles of SUA level were as follows: low tertile <5.0 mg/dl; intermediate tertile 5.0 to 6.4 mg/dl; and high tertile >6.4 mg/dl. There was a trend toward greater vessel volume in the high tertile group than in the low and intermediate tertile groups (19.4 +/- 3.7 vs 17.4 +/- 4.4 vs 16.7 +/- 4.1 mm(3)/mm, p = 0.05). There was no significant difference in lumen volume between the 3 groups. Plaque volume was significantly greater in the high than in the low tertile group (8.6 +/- 2.4 vs 6.7 +/- 2.2 mm(3)/mm, p = 0.01). IB-IVUS analysis demonstrated greater lipid (59.1 +/- 9.1% vs 49.7 +/- 10.9% vs 51.1 +/- 9.3%, p = 0.001) and less fibrous components (36.8 +/- 7.8% vs 44.3 +/- 7.8% vs 43.2 +/- 6.7%, p < 0.001) in the high than in the low and intermediate tertile groups. Multivariate analysis showed high SUA as an independent predictor of increasing lipid volume. In conclusion, elevated SUA level is associated with greater lipid content of coronary plaque in patients with ACS than in patients with normal levels. (C) 2015 Elsevier Inc. All rights reserved.

Background: Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study. Methods and Results: BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4-7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins. Conclusions: BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy.

Rationale: In right ventricular hypertrophy associatedwith severe pulmonary hypertension (PH), a shift of energy metabolism toward glycolysis occurs. There are few investigations regarding fatty acid metabolism in patients with PH and right ventricular hypertrophy. Objectives: To assess whether there is fatty acid accumulation in the hypertrophied right ventricle in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether this accumulation is related to hemodynamic variables obtained by right heart catheterization. Methods: To assess fatty acid accumulation in the right ventricle, 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) analog imaging was performed in control subjects (n = 16) and patients with CTEPH (n = 13) before (n = 13) and after (n = 8) pulmonary thromboendarterectomy. Measurements and Main Results: There was increased 123IBMIPP uptake in the right ventricle of subjects with CTEPH before pulmonary endarterectomy. Right ventricular 123I-BMIPP uptake decreased significantly after thromboendarterectomy (P = 0.003) in parallel with the change of hemodynamic variables. The right ventricular BMIPP uptake was significantly correlated with the mean pulmonary artery pressure (r = 0.51, P = 0.0228) but not with pulmonary vascular resistance (r = 0.39, P = 0.0932). Conclusions: This is the first study that uses 123I-BMIPP uptake imaging to show that fatty acid accumulates in the right ventricle of patients with CTEPH and that the increased accumulation is reversible after pulmonary thromboendarterectomy. This study suggests that this imaging modality may be useful for monitoring right ventricle metabolic functions in severe PH.

Background: Late and very late stent thrombosis after drug-eluting stent implantation is a major concern. The present study evaluated difference in the effects of sirolimus, paclitaxel and zotarolimus on endothelial cells. Methods: Mouse endothelial cells were seeded in a 6-well plate. Cells were cultured with an antiproliferative drug at the expected concentrations for each well for 24 hours before making 3 scratch lines with a pipette tip. After a 4.5 hour incubation period, 3 reference scratch lines, vertically across the original scratch lines, were made in the same way. The experiment was repeated at least 6 times (6 plates). Measurements were performed at 9 crossings of each well. Wound healing ratio was calculated as 1 - (distance of the first scratch/distance of the second scratch). % cell migration was calculated as (wound healing ratio at an expected drug concentration/wound healing ratio with no drug). × 100 Average % cell migration at 54 crossings of 6 plates was calculated. Results: Paclitaxel inhibited cell migration in a concentration-dependent manner. On the other hand, concentration-dependent inhibition was not observed for sirolimus or zotarolimus. Sirolimus showed a stronger inhibitory effect on migration of endothelial cells compared to zotarolimus. Conclusions: The difference in the effect of antiproliferative drugs of drug-eluting stents on endothelial cells may be associated with relatively faster re-endothelialization of zotarolimus-eluting stent compared to the 1st generation DES.

We report a case of right ventricular (RV) diastolic dysfunction due to a large hematoma posterior to the left ventricle (LV) after cardiac surgery. An 80-year-old woman underwent cardiac surgery. After surgery, her physical findings revealed right heart failure. Localized hematoma posterior to the pericardial space and the RV compression to the sternum were shown by computed tomography. Transthoracic Doppler echocardiography demonstrated restrictive physiology of the RV although there was no evidence of constrictive pericarditis. These findings suggest that RV diastolic dysfunction could have occurred due to the hematoma posterior to the LV. Since pleural effusion had persisted despite medical therapy, the hematoma was removed surgically. Soon after surgery, dyspnea and pretibial edema were diminished bilateral pleural effusion dramatically disappeared. RV diastolic dysfunction estimated by echocardiography was improved and RV compression disappeared.We speculate that there are two physiological mechanisms for the RV compression: (1) the localized hematoma elevated the intrapericardial pressure and (2) the hematoma shifted the entire heart to the sternum. In conclusion, this is the first case report of RV diastolic dysfunction due to large hematoma posterior to the LV.&lt . Learning objective: Localized hematoma posterior to the left ventricle can be a cause of right ventricular compression that leads to onset of severe right ventricular diastolic dysfunction.&gt .