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This study evaluated the time-to-time aerobic and anaerobic exercise intensities, calculated using the Global Positioning System (GPS), using laboratory measurements of individual physical fitness throughout the game in each female youth football player. In addition, we examine if the anaerobic exercise index calculated by only GPS data presents this evaluation to examine its validity. In the laboratory, the oxygen uptake (V̇O2) matched with moving speed was identified during an incremental exercise test on the treadmill, and the ventilatory (anaerobic) threshold was also analysed to identify individual aerobic and anaerobic exercise intensities. Using these laboratory data, time-to-time changes in individual relative running intensity (aerobic and anaerobic) were visualised from individual GPS data during a football game, and an individual’s sprint output (ability) during the game was evaluated. An index of running intensity and the percentage of anaerobic exercise over the game provided by the GPS software (equivalent distance index [%EDI] and anaerobic index [AI]) did not present the actual individual exercise intensity (ICC(2,1), absolute agreement=−0.031; P=0.596) and percentage of anaerobic exercise (ICC(2,1), absolute agreement=−0.003; P=0.698) values during the game, respectively. These findings suggest that only GPS measurement cannot present the individual actual exercise intensity during a football game because of different individual fitness levels to the same running speed.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

This study aimed to determine possible associations between sarcopenia and poor cardiovascular outcomes in patients with chronic heart failure after cardiac resynchronization therapy.This retrospective study evaluated 120 patients who underwent cardiac resynchronization therapy between March 2004 and June 2018. In total, 58 patients who underwent computed tomography within 30 days of cardiac resynchronization therapy implantation were eligible for inclusion, and their data were analyzed (25 women; 33 men; mean age 71.6 ± 8.7 years). Skeletal muscle area was measured at the third lumbar vertebra, and skeletal muscle index was calculated. Major adverse cardiovascular events included cardiovascular death, hospitalization due to heart failure, cerebral infarction, acute myocardial infarction and cardiac arrest.During the follow-up period (mean 868 ± 617 days), major adverse cardiovascular events occurred in 22 of 58 patients (38%). The patients were allocated to two groups according to sex-based tertiles of skeletal muscle index. The lowest tertile was defined as the low skeletal muscle index group. Kaplan-Meier survival analysis showed that the low skeletal muscle index group had a higher incidence of major adverse cardiovascular events (log-rank 4.38; P = 0.036). Cox proportional hazards regression analysis also showed that low skeletal muscle index values were significantly associated with major adverse cardiovascular events (hazard ratio 3.08; 95% confidence interval 1.26-7.66, P = 0.014).Decreases in skeletal mass index on computed tomography might predict the occurrence of major adverse cardiovascular events in patients with chronic heart failure who underwent cardiac resynchronization therapy. Geriatr Gerontol Int 2022; 22: 1013-1018.

Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.

PURPOSE The present study examined the effect of breath-hold without a Valsalva maneuver during isometric exercise on arterial blood pressure (ABP) and cerebral blood flow (CBF). METHODS Twenty healthy adults (15 men and five women) randomly performed only breath-hold without a Valsalva maneuver (BH), and an isometric handgrip exercise for 30 s at 40% of individual maximal voluntary contraction with continuous breathing (IHG) and with breath-hold without the Valsalva maneuver (IHG-BH). Mean ABP (MAP) and blood velocity in the middle (MCA Vmean) and posterior cerebral arteries (PCA Vmean) were continuously measured throughout each protocol. RESULTS MAP was elevated during the IHG-BH compared with IHG (P

NEW FINDINGS What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

Mobile cloud electrocardiography (C-ECG) can reduce the door-to-balloon time of acute coronary syndrome (ACS) patients, so we hypothesized it would also assist in transporting ACS-suspected patients to the optimal institutes.Methods and Results: Initially, 10 fire departments in Oita had 10 ambulances equipped with C-ECG. Ambulance crews recorded a 12-lead ECG from the patient at the first point of contact and transmitted them to 18 hospitals (13 institutions (PCII) with 24-h availability for percutaneous coronary intervention (PCI) and 5 regional core hospitals (RCH) without 24-h PCI) for analysis by a cardiologist. During 41 months, 476 ECGs suspected to be ACS were transmitted and analyzed. Of these, 24 ECGs transmitted to PCII were judged as not requiring PCI, and the patients were directly transported to a RCH (PCII-RCH); 35 ECGs sent to a RCH were judged as requiring PCI, and the patients were directly transported to a PCII (RCH-PCII). The prevalence of cardiovascular disease was significantly higher in the RCH-PCII group than in the PCII-RCH group (P0.01). There was no significant difference in the door-to-balloon time between the RCH-PCII and the group in which the C-ECG was sent to a PCII and the patients were transported directly to PCII (PCII-PCII) (49±14 vs. 59±20 min, P=0.14).Prehospital 12-lead ECG can assist in transporting ACS-suspect patients to the optimal treatment facility.

The properties of glucose changes in patients with chronic heart failure remain elusive. In the present study, we investigated the sequential changes of interstitial glucose concentrations in patients with chronic heart failure and heart disease who were not undergoing antidiabetic therapy.A glucose monitoring device (FreeStyle Libre Pro) was attached to the backside of an upper arm and the interstitial glucose concentration was monitored every 15 minutes for 1 week. Eleven patients with chronic heart failure (Heart failure (+) ) and 7 patients with chronic heart diseases but not with heart failure (Heart failure (-) ) were enrolled. The average level and peak value of interstitial glucose concentrations, and the duration of hyperglycemia (≥ 140 mg/dL) were not significantly different between Heart failure (+) and Heart failure (-). The duration of hypoglycemia (< 80 mg/dL) was significantly longer and the trough value was significantly lower in Heart failure (+) compared with Heart failure (-). Most of the patients in Heart failure (+) were exposed to a long duration of hypoglycemia from midnight to morning. Importantly, none of the patients who showed hypoglycemia complained of any subjective symptoms during hypoglycemia. Malabsorption may be one of the mechanisms of hypoglycemia.In summary, patients with chronic heart failure are at risk of developing hypoglycemia even if they do not undergo any antidiabetic therapy.

Aims Cardiac hypertrophy is a compensatory response to pressure overload, leading to heart failure. Recent studies have demonstrated that Rho is immediately activated in left ventricles after pressure overload and that Rho signalling plays crucial regulatory roles in actin cytoskeleton rearrangement during cardiac hypertrophic responses. However, the mechanisms by which Rho and its downstream proteins control actin dynamics during hypertrophic responses remain not fully understood. In this study, we identified the pivotal roles of mammalian homologue of Drosophila diaphanous (mDia) 1, a Rho-effector molecule, in pressure overload-induced ventricular hypertrophy. Methods and results Male wild-type (WT) and mDia1-knockout (mDia1KO) mice (10–12 weeks old) were subjected to a transverse aortic constriction (TAC) or sham operation. The heart weight/tibia length ratio, cardiomyocyte cross-sectional area, left ventricular wall thickness, and expression of hypertrophy-specific genes were significantly decreased in mDia1KO mice 3 weeks after TAC, and the mortality rate was higher at 12 weeks. Echocardiography indicated that mDia1 deletion increased the severity of heart failure 8 weeks after TAC. Importantly, we could not observe apparent defects in cardiac hypertrophic responses in mDia3-knockout mice. Microarray analysis revealed that mDia1 was involved in the induction of hypertrophy-related genes, including immediate early genes, in pressure overloaded hearts. Loss of mDia1 attenuated activation of the mechanotransduction pathway in TAC-operated mice hearts. We also found that mDia1 was involved in stretch-induced activation of the mechanotransduction pathway and gene expression of c-fos in neonatal rat ventricular cardiomyocytes (NRVMs). mDia1 regulated the filamentous/globular (F/G)-actin ratio in response to pressure overload in mice. Additionally, increases in nuclear myocardin-related transcription factors and serum response factor were perturbed in response to pressure overload in mDia1KO mice and to mechanical stretch in mDia1 depleted NRVMs. Conclusion mDia1, through actin dynamics, is involved in compensatory cardiac hypertrophy in response to pressure overload.

Background: The onset of acute myocardial infarction (AMI) is related to weather conditions, but the impact of age on gender differences in the AMI onset–weather association has not been elucidated. Methods and Results: We analyzed the Oita AMI Registry and obtained data for 403 enrolled patients. To examine the impact of age, we categorized the patients into 4 groups: young (age ≤65 years) women (n=20); young men (n=123); elderly (age >65 years) women (n=84); and elderly men (n=176). The analyzed meteorological factors were maximum and minimum temperature, intraday temperature difference, average humidity, and average atmospheric pressure. The young women group had a higher minimum temperature (17.7±5.7℃ vs. 13.8±8.2℃, P=0.04), lower intraday temperature difference (7.0±2.6℃ vs. 8.4±2.9℃, P=0.03), higher average humidity (74.5±12.1% vs. 68.1±12.0%, P=0.03), and lower average atmospheric pressure (1,009.5±5.0 hPa vs. 1,012.9±5.8 hPa, P=0.01) than the young men group on the onset day. In the elderly groups, there was no significant difference in meteorological variables except for the intraday temperature difference 2 days before AMI onset. Conclusions: AMI onset appears to be more sensitive to weather conditions (i.e., minimum temperature, average atmospheric pressure, and average humidity) in young patients than in elderly patients. In particular, young women had AMI on days with low intraday temperature difference and high humidity relative to men.

Background Atrial fibrillation (AF) is associated with heart failure (HF) rehospitalization in patients with heart failure with preserved ejection fraction (HFpEF). Objective We tested the hypothesis that catheter ablation of AF could reduce HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF. Methods Eighty-five consecutive HFpEF (EF ≥ 50% and a history of HF hospitalization) patients diagnosed as AF by 12-lead electrocardiogram were retrospectively analyzed. Thirty-five patients who received catheter ablation (ABL group) were compared with 50 patients treated by antiarrhythmic drugs and/or beta-blockers (CNT group). The primary endpoint was rehospitalization due to HF. Results The patients characteristics did not differ between the two groups including, age (71 ± 8 vs 71 ± 13 years; P = .637), female sex (34% vs 36%; P = .870), mean plasma brain natriuretic peptide (145 ± 112 vs 195 ± 153 pg/mL; P = .111), mean left ventricular ejection fraction (62% ± 8% vs 61% ± 9%; P = .624), and type of AF (nonparoxysmal AF 60% vs 62%; P = .852). Amiodarone was continued 40% (14 out of 35) and 40% (20 out of 70) in ABL and CNT groups, respectively (P = 1.000). Neither major complication nor major side effect was observed during the follow-up period. During a mean follow-up period of 792 ± 485 days, Kaplan-Meier curve analysis showed that significantly more patients in the ABL group were free from HF rehospitalization (log-rank P = .0039). Additionally, multivariate analysis revealed that catheter ablation of AF was the only preventive factor of HF rehospitalization (OR = 0.15; 95% CI: 0.04-0.46; P Conclusions Catheter ablation of AF reduced HF rehospitalization compared with conventional pharmacotherapy in patients with HFpEF in our institute. Multicenter randomized study is warranted to confirm the result.

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005–0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (−0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.

Change in cardiac output (Q) contributes to cerebral blood flow (CBF) regulation at rest and even during steady-state exercise. At the onset of cycling exercise, Q increases acutely and largely via muscle pump. The purpose of the present study was to examine whether onset exercise-induced a large increase in Q contributes to CBF regulation at the onset of exercise.In 20 young healthy participants (10 males and 10 females), Q, mean arterial pressure (MAP), and mean blood velocities of middle and posterior cerebral arteries (MCA Vm and PCA Vm) were continuously measured during light cycling exercise for 3 min.At the onset of exercise, Q increased acutely to the peak (P 0.001), while the CBF peak responses were not significantly higher than the values during the steady-state exercise (MCA Vm and PCA Vm; P = 0.183 and P = 0.101, respectively). The change in Q was correlated with that of MCA Vm or PCA Vm from resting baseline to the steady-state exercise (r = 0.404, P 0.001 and r = 0.393, P 0.001, respectively). However, the change in Q was not correlated with that of MCA Vm or PCA Vm at the onset of exercise (P = 0.853 and P = 0.893, respectively). Any sex differences in the onset response of peripheral and cerebral hemodynamics to exercise were not observed.These findings suggest that the acute change in Q does not contribute to CBF regulation at the onset of exercise for protecting cerebral vasculature against a large and acute elevation in Q at the onset of exercise.

Different cerebral blood flow (CBF) responses to exercise between the posterior cerebral artery (PCA) and vertebral artery (VA) have been previously observed, though the physiological mechanisms remain unknown. There is regional heterogeneity in sympathetic innervation between the PCA and VA, which may affect CBF regulation, especially during sympathoexcitation. Thus, in the present study, we hypothesized that different CBF regulatory mechanisms between PCA and VA contribute to heterogeneous CBF responses to isometric exercise. To test this hypothesis, in thirteen healthy young men, dynamic cerebral autoregulation (CA) and cerebrovascular CO

Background: The mobile cloud electrocardiography (C-ECG) system is useful for reducing door-to-balloon (DTB) time in patients with acute coronary syndrome (ACS), but few studies have reported the usefulness of the C-ECG system across a wide provincial prefecture, such as Oita, in Japan. Methods and Results: On 17 April 2017, the C-ECG system was integrated into the Oita remote image transmission system, in 10 ambulances of 10 respective fire departments in Oita Prefecture. During 6 months, 162 ECG indicating suspected ACS were transmitted to 18 hospitals using the C-ECG system. Of 162 patients, 17 who received emergency percutaneous coronary intervention (PCI) were assigned to the cloud group (mean age, 71±11 years). The control group consisted of 29 consecutive ACS patients who were transported to Oita University Hospital without using the C-ECG system (mean age, 66±12 years). Another 40 consecutive patients were diagnosed with ACS before transportation to Oita University Hospital, and were assigned to the diagnosed group (mean age, 70±14 years). DTB time (70±26 min vs. 96±24 min, P

Reducing complications at the puncture site after percutaneous coronary intervention (PCI) is important. The diameter of a 6.5-French (Fr) sheathless guiding catheter (GC) is smaller by approximately 2-Fr compared to a 6-Fr conventional sheath. In the present study, we investigated the post-PCI puncture site complications of a transradial approach in each gender while using a 6.5-Fr sheathless GC.Our study consisted of 332 patients who underwent transradial coronary intervention (TRI) between August 2017 and July 2019. We classified the patients into either the 6.5-Fr sheathless GC (Asahi, Intecc, Aichi, Japan) Group (Sheathless group: n = 182 males, 58 females) or the 6-Fr sheathed GC Group (Sheathed group: n = 150 males, 36 females). We determined the complications at the puncture site: oozing, subcutaneous hemorrhage, formation of hematoma, pseudoaneurysms, and peripheral neuropathy. The body mass index of the patients was greater in the sheathless GC group compared to the sheathed GC group (24.5 ± 3.5 kg/mThe use of the 6.5-Fr sheathless GC system in a transradial approach reduced the complications at the puncture site in female patients. The 6.5-Fr sheathless GC system may be a safe option for them compared to the conventional sheath system.

The present study examined the effect of breath-hold without a Valsalva maneuver during isometric exercise on arterial blood pressure (ABP) and cerebral blood flow (CBF).Twenty healthy adults (15 men and five women) randomly performed only breath-hold without a Valsalva maneuver (BH), and an isometric handgrip exercise for 30 s at 40% of individual maximal voluntary contraction with continuous breathing (IHG) and with breath-hold without the Valsalva maneuver (IHG-BH). Mean ABP (MAP) and blood velocity in the middle (MCA VMAP was elevated during the IHG-BH compared with IHG (P 0.001) and BH (P = 0.001). Similarly, both MCA VThese results indicate that during isometric exercise, a breath-hold enhances an exercise-induced increase in MAP and, consequently, MCA V

The handgrip exercise, a small muscle exercise, is useful for exercise therapy, particularly in the elderly and bedridden patients. The isometric handgrip (IHG) exercise has been utilized in training programs to reduce resting blood pressure; however, the acute effects of the IHG exercise on cognitive performance are not fully understood. The present study aimed to investigate the effect of an intermittent IHG exercise protocol with short exercise duration, which minimizes the arterial blood pressure response to exercise, on cognitive performance. Twenty-two young healthy subjects performed the intermittent IHG exercise protocol, which consisted of 30-s IHG and 45-s recovery × 16 trials; the exercise intensity of the IHG exercise was 30% of the maximal voluntary contraction. Cognitive performance was evaluated before and after the exercise with the Go/No-Go and memory recognition tasks. Specifically, the reaction time (RT) and performance accuracy were measured. The intermittent IHG exercise protocol did not change the RT or performance accuracy of either the Go/No-Go task (P = 0.222 and P = 0.260, respectively) or the memory recognition task (P = 0.427 and P = 0.245, respectively). These findings suggest that the intermittent IHG exercise protocol with short exercise duration may not provide enough stimulation to improve cognitive performance despite being useful as a safe exercise therapy in the elderly and in patients with cardiovascular disease.

Previous studies have reported that even a single bout of dynamic exercise improves cognitive performance. However, the acute effect of the interval handgrip (HG) exercise protocol, which is effective in reducing resting blood pressure, on cognitive performance is poorly understood. Cognitive performance was assessed in 17 young healthy subjects before and after a resting control (e.g., time control) and the interval HG exercise (Exercise), which consisted of four trials of 2-min HG exercise at 25% of maximum voluntary contraction with 3-min recovery in between each trial. Mean arterial blood pressure (MAP) and middle cerebral artery blood velocity (MCA V) were measured continuously throughout the experiment. Memory recognition and executive function were assessed using memory recognition and Go/No-Go tasks, respectively. During interval HG exercise, MAP and mean MCA V increased from the resting baseline condition (both P < 0.049) and returned to the resting baseline levels during recovery after the interval HG exercise (both P = 1.000). The reaction time and performance accuracy of the memory recognition task did not change in either the time control condition or Exercise condition (P = 0.514 and P = 0.414 respectively). However, the changes in reaction time of Go/No-Go task from the baseline in Exercise condition was significantly shorter than that in time-control condition (P = 0.004) without affecting performance accuracy (P = 0.482). The results of the present study show that an acute interval HG exercise could improve the processing speed in executive function despite no post-exercise improvement in hemodynamic parameters in young healthy subjects. These findings suggest that the interval HG exercise is a useful exercise mode that can be expected to have a positive effect on the processing speed in executive function regardless of cardiovascular adaptation to exercise.

Pulmonary tumor thrombotic microangiopathy (PTTM) is histologically characterized by micro tumor cell embolism and intimal fibrocellular proliferation of pulmonary arteries or arterioles. We report a secondary case of PTTM associated with extramammary Paget's disease (EMPD). The patient was a 72-year-old man with exertional dyspnea. Clinical examinations found he had pulmonary hypertension and multiple osteolytic lesions of vertebra. Cytological analysis of pulmonary wedge artery sample detected malignant cells and he was dead before treatment was started. Multiple tumor embolisms (>17) were identified in pulmonary arteries or arterioles at autopsy, consistent with PTTM. Metastatic nodules were found in liver and lymph node. Furthermore, disseminated carcinomatosis of the bone marrow (DCBM) was seen. Immunostaining results pointed out that tumor cells possessed mammary gland phenotype. He had 4-years history of EMPD in the left axilla without recurrence, and immunohistochemistry results were the same as the autopsy specimen. Thus, we diagnosed the primary site of PTTM to be EMPD. Our case highlights the usefulness of the recent proposed classification of PTTM, potential association between PTTM and DCBM, and the necessity for long-term follow-up in EMPD. EMPD can rarely cause PTTM to manifest as a paraneoplastic syndrome.

The onset of acute myocardial infarction (AMI) has been reportedly related to weather conditions. The aim of this study was to investigate the impact of weather conditions on AMI onset. Our study population consisted of 274 patients enrolled in the Oita AMI Registry who were admitted with AMI between June 2012 and May 2013. We divided the 365 days of the year into the four seasons: spring (March, April, May), summer (June, July, August), autumn (September, October, November), and winter (December, January, February). We classified each day as a day of onset of AMI (onset day) or a day of non-onset of AMI (non-onset day). Information on maximum temperature, minimum temperature, mean humidity, and mean atmospheric pressure was obtained from the Japan Meteorological Agency. In summer, the temperatures and intraday temperature differences were significantly lower on onset days than on non-onset days. Receiver operating characteristic analysis for predicting AMI onset in each season showed that the maximum temperature 2 days before AMI onset in summer had the largest area under the curve (AUC = 0.72, p = 0.0005). Our analysis demonstrated that there exist specific weather conditions that influence AMI onset in each season in Oita prefecture. AMI onset in summer was particularly associated with the maximum temperature 2 days before AMI onset.

Hyperleptinemia and Atrial FibrillationBackground Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF. Methods and Results Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P < 0.01). In WT-HFD mice, hyperleptinemia was observed as expected. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob-HFD mice (P < 0.01). In isolated perfused hearts, the interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (P < 0.05). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT-HFD mice, which was not observed in Ob-HFD mice (P < 0.05). Upregulation of collagen1, collagen3, α-smooth muscle actin, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA levels was noted in WT-HFD mice LA, but attenuated in Ob-HFD mice LA. Conclusions Our findings suggest that hyperleptinemia exacerbates HFD-mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF.

The present case report describes a 59-year-old female with manifest Wolff–Parkinson–White syndrome and severe left ventricular (LV) dysfunction, however, there was no indication of heart palpitations. The polarity of delta is consistent with the features of the right anteroseptal accessory pathways (APs). The echocardiography showed a remarkable dyssynchrony of the LV wall motion. To circumvent the cardiac dysfunctions, radiofrequency catheter ablation (RFCA) was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and the clinical reports observed 6 months following RFCA showed that the LV ejection fraction had been improved from 13% up to 48%, in addition to the improvement in other parameters. The RFCA prevented her from receiving a cardiac resynchronization therapy defibrillator as well as a heart transplantation.

Background Cardiac sarcoidosis is a cause of epicarditis and sustained life-threatening ventricular arrhythmias. These arrhythmias occasionally arise from epicardial. Positron emission tomogramphy-comututed tomography (PET-CT) is useful for diagnosis with sarcoidosis. However, the usefulness for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis is unknown. Objective We hypothesized that the evaluation of pericardial fat inflammation could identify high-risk sarcoidosis patients for ventricular arrhythmias. Methods We enrolled 20 consecutive patients with cardiac sarcoidosis performed PET-CT between August 2016 and December 2018. In each case, we measured the maximum standardized uptake value (SUVmax) of pericardial fat around the left atrium, both ventricules, atrioventricular groove, and left main coronary. Results Seven patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). VT/VF patients had significantly more complete right bundle branch block (P=0.035), larger left atrial dimension (P=0.021), larger left ventricular end-diastolic dimension (P=0.005), lower ejection fraction (P=0.007), and higher E/e' (P=0.004). SUVmax of pericardial fat in the roof of left atrium (LA) and left ventricular (LV) with VT/VF patients were significantly higher than non-VT/VF patients (LA: 1.63 vs 1.32, P=0.0311; LV: 1.84 vs 1.26, P=0.045). The cut-off values of SUVmax derived from the ROC curve in the roof of LA and LV are 1.47 and 1.59 respectively. The Kaplan Meire estimator showed that high SUVmax patients in the roof of LA had significantly more detection of NSVT. Conclusions Our results suggest the relationship between SUVmax and VT/VF occurrence in patients with cardiac sarcoidosis. The evaluateon of SUVmax may be useful for VT/VF risk stratification.

Cardiac Sarcoidosis and CRT OutcomeIntroduction Cardiac resynchronization therapy (CRT) has been shown to be effective for patients with chronic heart failure; however, the efficacy of CRT in patients with cardiac sarcoidosis (CS) has not been established. Methods We compared the outcomes of patients with CS who received CRT to patients with dilated cardiomyopathy (DCM). The incidence of major adverse cerebral and cardiovascular events (MACCE) in 11 consecutive CS patients (8 females; mean age, 66 ± 8.0 years) who received CRT were compared with 29 DCM patients (9 females; mean age, 70 ± 8.9 years). Results Females and patients with previous right ventricular pacing were largely included in the comparison of CS and DCM patients (P

This case report describes a 43-year-old man who temporarily survived cardiac arrest that was prospectively related to ventricular fibrillation due to the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Prior to admission to our hospital, he was asymptomatic for ALCAPA syndrome. Emergent coronary angiography revealed that the dilated right coronary artery was connected with extensive collateral vessels to the left coronary artery. The origin of the latter was in the pulmonary artery. Moreover, coronary steal phenomenon was identified by examining the pulmonary arterial blood oxygen saturation. The patient later died of acute decompensated acidosis.

BACKGROUND AND OBJECTIVES Recently, it was reported that mast cells (MCs) could underlie the mechanisms of several cardiovascular diseases. However, the role of MCs in diabetes-induced atrial fibrillation (AF) has not been notably investigated. We tested the hypothesis that MC deficiency attenuates hyperglycemia-induced AF in mice. METHODS AND RESULTS Mast cell-deficient W/W(v) mice, and congenic +/+ littermates (WT) were divided into either the vehicle (VEH)-injection group or the streptozotocin (STZ)-injection group (MCKO-VEH, MCKO-STZ, WT-VEH, and WT-STZ groups). On day 28 of our studies, we observed that (1) STZ-induced hyperglycemia increased MC infiltration in the left atrium (LA) in WT mice (P < 0.01), (2) atrium isolated from the WT-STZ group showed inhomogeneous interstitial fibrosis, abundant infiltration of macrophages, and enhanced apoptosis compared to the WT-VEH group (P < 0.01, P < 0.01, P < 0.05, respectively). However, the changes observed in the WT-STZ group were significantly attenuated in the MCKO-STZ mice. In addition, we observed that (3) messenger RNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, transforming growth factor-β, and collagen-1 in the LA were increased in the WT-STZ group, but not in the MCKO-STZ group, (4) STZ-induced hyperglycemia increased AF induction and prolonged interatrial conduction time in the WT mice, which were not observed in the MCKO mice, and that (5) hyperglycemia-enhanced atrial production of reactive oxygen species (ROS) was equally observed in the WT and MCKO mice. CONCLUSIONS Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.

On the basis of homogeneous liquid-liquid extraction (HoLLE) with Zonyl FSA to plating water containing 1 mg palladium, 96.6% of the palladium was extracted into the sedimented liquid phase. After phase separation, the volume ratio (Va/Vs) of the aqueous phase (Va) and the sedimented liquid phase (Vs) was 556 (50 mL → 0.09 mL). The assessment of the potential implementation of this procedure to wastewater treatment showed that HoLLE was satisfactorily achieved when the volume was scaled up to 1000 mL. Moreover, HoLLE was conducted to real palladium plating wastewater generated in the plating industry. 94.5% of the palladium was extracted into the sedimented liquid phase. After phase separation, the volume ratio (Va/Vs) of the aqueous phase (Va) and the sedimented liquid phase (Vs) was 500 (50 mL → 0.1 mL). In addition, HoLLE could separate palladium from coexisting metals in real plating wastewater. This knowledge is expected to lead to the development of new separation and concentration technologies of rare metals from real plating wastewater.

Cardiac resynchronization therapy (CRT) has been established as a treatment for patients with chronic heart failure (HF). We tested the hypothesis that assessment of coronary flow reserve (CFR) predicts the long-term outcome of CRT. The study consisted of 114 HF patients implanted with a CRT device for the treatment of advanced HF between April 2010 and April 2018. After excluding patients that withdrew from long-term follow-up and patients missing a baseline CFR measurement, we enrolled 53 eligible patients. CFR was determined non-invasively by transthoracic echocardiography. Based on the ROC curve for predicting the appearance of major adverse cerebral and cardiovascular events (MACCE), the level of preserved CFR was set at >1.35 in responders. Accurate follow-up information (mean 873 ± 498 days) was obtained in 23 patients with a preserved CFR (16 females; mean age 71 ± 7.9 years) and 11 patients with a depressed CFR (5 females; mean age, 73 ± 7.6 years) in responders. Kaplan–Meier survival analysis demonstrated that the depressed CFR group had a higher prevalence of MACCE than the preserved CFR group (log rank, 9.83; p = 0.0021). Multivariate analysis revealed that depressed CFR was associated with MACCE (hazard ratio 4.88, 95% confidence interval 1.13–26.5, p = 0.0329). Our results suggest that the assessment of CFR predicts the outcome in responders to CRT. Preservation of coronary circulation flow might underlie one of the mechanisms for a better response to CRT in responders.

Background Epicardial adipose tissue (EAT) is associated with atrial fibrillation (AF), but the underlying mechanisms remain to be fully elucidated. Objective The purpose of this study was to examine, using human left atrial appendage (LAA) samples, the interactive relationship between the EAT profile and atrial myocardial fibrosis through histologic and biochemical analyses. Methods LAA samples were obtained from 59 consecutive AF patients during cardiovascular surgery. In histologic analysis, adipose tissue, atrial myocardial fibrosis, EAT fibrosis, macrophage infiltration, and matrix metalloproteinase-2 and hypoxia-inducible factor-1α (Hif-1α) expression were evaluated in LAA sections. In biochemical analysis, proinflammatory/fibrotic proteins in EAT, total collagen in left atrial (LA) myocardium, angiopoietin-like protein-2 (Angptl2)-related proteins in EAT, and proinflammatory/fibrotic proteins in serum were evaluated. Results Histology revealed that the severity of fibrotic remodeling of EAT was associated with LA myocardial fibrosis. Immunohistochemical and electron microscopic findings revealed that fibrotic remodeling of EAT was associated with infiltration of macrophages and myofibroblasts. Protein concentration analysis demonstrated that the total collagen in the LA myocardium was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor, and matrix metalloproteinase-2 and matrix metalloproteinase-9 in EAT. The proinflammatory and profibrotic cytokines/chemokines in EAT and the total collagen in the LA were also positively correlated with Angptl2 in EAT. Conclusion Our study demonstrated that fibrotic remodeling and cytokines/chemokines in peri-LA EAT were associated with atrial myocardial fibrosis as a substrate of AF. Our results also suggested that overexpression of Hif-1α and Angptl2 may be involved in these processes.

Background: Obesity, characterized by systemic low-grade inflammation, is considered a well-known risk for atrial fibrillation. In fact, IL-10 (interleukin 10), which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypotheses forwarding that genetic deletion of IL-10 exacerbates high-fat diet (HFD)–induced obesity-caused atrial inflammation, lipidosis, fibrosis, and fibrillation and that IL-10 therapy inhibits this pathology. Methods: Eight- to 10-week-old male CL57/B6 (wild-type) mice and IL-10 knockout mice were divided into a 12-week HFD group and a 12-week normal-fat diet (NFD) group, respectively. In addition, the effect of IL-10 administration was also investigated. RESULTS: HFD-induced obesity for 12 weeks significantly depressed serum levels of IL-10 but were found to increase several proinflammatory cytokines in wild-type mice. Adverse atrial remodeling, including atrial inflammation, lipidosis, and fibrosis, was induced in both wild-type and IL-10 knockout mice by HFD. Vulnerability to atrial fibrillation was also significantly enhanced by HFD. With regard to epicardial and pericardial adipose tissue, the total amount of epicardial adipose tissue+pericardial adipose tissue volume was increased by HFD. Besides, proinflammatory and profibrotic cytokines of epicardial adipose tissue+pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by HFD. These HFD-induced obesity-caused adverse effects were further exaggerated in IL-10 knockout mice in comparison to wild-type mice. Systemic IL-10 administration markedly ameliorated HFD-induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation, in addition to improving the quality of epicardial adipose tissue+pericardial adipose tissue. Conclusions: Our results highlight IL-10 treatment as a potential therapeutic approach to limit the progression of HFD-induced obesity-caused atrial fibrillation.

Background Coagulation factor Xa (FXa) promotes thrombus formation and exacerbates inflammation via activation of protease-activated receptor (PAR)-2. We tested the hypothesis of whether administration of direct oral anticoagulant, rivaroxaban, would attenuate transverse aortic constriction (TAC)-induced atrial inflammatory fibrosis and vulnerability to atrial fibrillation (AF) in mice. Methods Ten-week-old male CL57/B6 mice were divided into a sham-operation (CNT) group and TAC-surgery group. These two groups were then subdivided into vehicle (VEH) and rivaroxaban (RVX) treatment (30 μg/g/day) groups. We assessed PAR-2 expression in response to TAC-related stimulation using rat cultured cells. Results TAC-induced left atrial thrombus formation was not observed in the TAC-RVX group. Cardiac PAR-2 upregulation was observed in both TAC groups. In the quantitative analysis of mRNA levels, cardiac PAR-2 upregulation was attenuated in the TAC-RVX group compared to TAC-VEH group. In histological evaluation, the TAC-VEH group showed cardiac inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were attenuated by RVX administration. Electrophysiological examination revealed that AF duration in the TAC group was shortened by RVX administration. TAC-induced protein overexpression of monocyte chemoattractant protein-1, and mRNA overexpression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the left atrium was suppressed by RVX treatment. In cardiac fibroblasts, persistent intermittent stretch upregulated PAR-2, which was suppressed by RVX pre-incubation. Conclusions These observations demonstrate that coagulation FXa inhibitor probably has a cardioprotective effect against pressure-overload-induced atrial remodeling.

Reactive oxygen species (ROS) are the main facilitators of cardiovascular complications in diabetes mellitus (DM), and the ROS level is increased in cultured cells exposed to high glucose concentrations or in diabetic animal models. Emerging evidence shows that mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase are dominant mechanisms of ROS production in the diabetic heart. Hyperpolarization of the mitochondrial inner membrane potentials and impaired mitochondrial function promote ROS production in the mitochondria of the diabetic heart. Uncoupling proteins are upregulated and may reduce the ROS level by depolarizing the mitochondrial inner membrane potential. NADPH oxidase is another major site of ROS production and its contribution to DM-induced ROS increase has been elucidated not only in vascular smooth muscle cells and endothelial cells, but also in cardiomyocytes. Protein kinase C, angiotensin II, and advanced glycation endproducts (AGEs)/receptor for AGEs can activate NADPH oxidase. Increased intracellular calcium level mediated via the Na(+)-H(+) exchanger and subsequent activation of Ca(2+)/calmodulin-dependent protein kinase II may also activate NADPH oxidase. This review presents the current understanding of the mechanisms of ROS production, focusing especially on the roles of mitochondria and NADPH oxidase.

Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high-fat diet (HFD)-induced hyperleptinemia exacerbates atrial fibrosis and AF.Eight-week-old male C57BL/6 (WT) and leptin-deficient ob/ob (Ob) mice were treated with a normal-fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription-polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P0.01). In WT-HFD mice, hyperleptinemia was observed as expected. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT-HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob-HFD mice (P0.01). In isolated perfused hearts, the interatrial conduction time was prolonged in WT-HFD mice, but not in Ob-HFD mice (P0.05). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT-HFD mice, which was not observed in Ob-HFD mice (P0.05). Upregulation of collagen1, collagen3, α-smooth muscle actin, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA levels was noted in WT-HFD mice LA, but attenuated in Ob-HFD mice LA.Our findings suggest that hyperleptinemia exacerbates HFD-mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity-related AF.

Background Monocyte chemoattractant protein-1 (MCP-1)-mediated inflammatory mechanisms have been shown to play a crucial role in atrial fibrosis induced by pressure overload. In the present study, we investigated whether left atrial endothelial cells would quickly respond structurally and functionally to pressure overload to trigger atrial fibrosis and fibrillation. Methods and results Six-week-old male Sprague–Dawley rats underwent suprarenal abdominal aortic constriction (AAC) or a sham operation. By day 3 after surgery, macrophages were observed to infiltrate into the endocardium. The expression of MCP-1 and E-selectin in atrial endothelium and the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and ED1 in left atrial tissue were enhanced. Atrial endothelial cells were irregularly hypertrophied with the disarrangement of lines of cells by scanning electron microscopy. Various-sized gap formations appeared along the border in atrial endothelial cells, and several macrophages were located just in the endothelial gap. Along with the development of heterogeneous interstitial fibrosis, interatrial conduction time was prolonged and the inducibility of atrial fibrillation by programmed extrastimuli was increased in the AAC rats compared to the sham-operated rats. Conclusions Atrial endothelium responds rapidly to pressure overload by expressing adhesion molecules and MCP-1, which induce macrophage infiltration into the atrial tissues. These processes could be an initial step in the development of atrial remodeling for atrial fibrillation.

Recently, it was reported that mast cells (MCs) could underlie the mechanisms of several cardiovascular diseases. However, the role of MCs in diabetes-induced atrial fibrillation (AF) has not been notably investigated. We tested the hypothesis that MC deficiency attenuates hyperglycemia-induced AF in mice.Mast cell-deficient W/W(v) mice, and congenic +/+ littermates (WT) were divided into either the vehicle (VEH)-injection group or the streptozotocin (STZ)-injection group (MCKO-VEH, MCKO-STZ, WT-VEH, and WT-STZ groups). On day 28 of our studies, we observed that (1) STZ-induced hyperglycemia increased MC infiltration in the left atrium (LA) in WT mice (P0.01), (2) atrium isolated from the WT-STZ group showed inhomogeneous interstitial fibrosis, abundant infiltration of macrophages, and enhanced apoptosis compared to the WT-VEH group (P0.01, P0.01, P0.05, respectively). However, the changes observed in the WT-STZ group were significantly attenuated in the MCKO-STZ mice. In addition, we observed that (3) messenger RNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, transforming growth factor-β, and collagen-1 in the LA were increased in the WT-STZ group, but not in the MCKO-STZ group, (4) STZ-induced hyperglycemia increased AF induction and prolonged interatrial conduction time in the WT mice, which were not observed in the MCKO mice, and that (5) hyperglycemia-enhanced atrial production of reactive oxygen species (ROS) was equally observed in the WT and MCKO mice.Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.

BACKGROUND AND PURPOSE Resveratrol is a polyphenol abundantly found in grape skin and red wine. In the present study, we investigated whether resveratrol exerts protective effects against cardiac ischaemia/reperfusion and also explored its mechanisms. EXPERIMENTAL APPROACH Infarct size and functional recovery in rat isolated perfused hearts subjected to no-flow global ischaemia followed by reperfusion were measured. Cultured neonatal rat cardiomyocytes were exposed to H(2)O(2) (100 µmol·L(-1)) to induce cell injury. Intracellular ion concentrations were measured using specific dyes. Western blotting was used to quantify protein expression levels. KEY RESULTS In rat isolated perfused hearts, treatment with resveratrol (20 and 100 µmol·L(-1)) 15 min before ischaemia considerably improved left ventricular functional recovery and infarct size. In cultured neonatal rat cardiomyocytes, resveratrol significantly attenuated the increase in reactive oxygen species (ROS) and loss of mitochondrial inner membrane potential. Resveratrol also suppressed the increase in intracellular concentrations of Na(+) ([Na(+)](i)) and Ca(2+) ([Ca(2+)](i)) after H(2)O(2) application; however, it did not suppress the ouabain-induced [Ca(2+) ](i) increase. By measuring changes in intracellular pH recovery after acidification, we also confirmed that acid-induced activation of the Na(+)-H(+) exchanger (NHE) was prevented by pretreatment with resveratrol. Furthermore, resveratrol inhibited the H(2)O(2)-induced translocation of PKC-α from the cytosol to the cell membrane; this translocation is believed to activate NHE. CONCLUSION AND IMPLICATIONS Resveratrol exerts cardioprotection by reducing ROS and preserving mitochondrial function. The PKC-α-dependent inhibition of NHE and subsequent attenuation of [Ca(2+)](i) overload may be a cardioprotective mechanism.

Diabetes mellitus is a risk factor for heart failure. Increased reactive oxygen species (ROS) have been proposed as a possible mechanism of cardiac dysfunction in diabetic patients. However, the mechanisms of ROS increase are still elusive. We hypothesized that activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) induced by impaired intracellular Ca(2+) ([Ca(2+)](i)) metabolism may stimulate ROS production in the diabetic heart. Cultured cardiomyocytes from neonatal rats were exposed to high glucose concentrations (25 mmol/L) and ROS levels were analyzed in 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H(2)DCFDA)-loaded cells by flow cytometry analysis. Exposure to high glucose concentrations for 24h significantly increased CM-H(2)DCFDA fluorescence, which was significantly inhibited by 1,2-bis (o-aminophenoxy) ethane- N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), a [Ca(2+)](i) chelator, and KB-R7943, an inhibitor of the Na(+)-Ca(2+) exchanger (NCX) in the reverse mode. These results indicate that [Ca(2+)](i) increase by NCX activation may induce ROS increase following exposure to high glucose concentrations. We confirmed that exposure to high glucose concentrations significantly increased [Ca(2+)](i), which was inhibited by KB-R7943. Na(+)-H(+) exchanger (NHE) is a key factor in [Ca(2+)](i) metabolism, and is known to activate NCX by increasing the intracellular Na(+) ([Na(+)](i)) level. We showed that the expression of NHE isoform 1 and NHE activity increased following exposure to high glucose concentrations by evaluating protein expressions and intracellular pH recovery from acid loading. Exposure to high glucose concentrations up-regulated phosphorylated CaMKII expression in cardiomyocytes that was inhibited by KB-R7943. Further, autocamtide 2-related inhibitory peptide (AIP), a CaMKII inhibitor, significantly attenuated the ROS increase following exposure to high glucose concentrations. We confirmed these results obtained in in vitro experiments in an animal model of diabetes. ROS level and components of NADPH oxidase, p47phox and p67phox were up-regulated in streptozotocin-induced diabetic rat heart, which were attenuated by KN-93, a CaMKII inhibitor. Consistently, expression of phosphorylated CaMKII was increased in the diabetic heart. Activation of CaMKII by impaired [Ca(2+)](i) metabolism may be a mechanism of ROS increase in the heart with diabetes mellitus.

Background The influence of glucose fluctuations (GF) on cardiovascular complications of diabetes mellitus (DM) has been attracting much attention. In the present study, whether GF increase susceptibility to ischemia/reperfusion in the heart was investigated. Methods and results Male rats were randomly assigned to either a control, DM, and DM with GF group. DM was induced by an injection of streptozotocin, and glucose fluctuation was induced by starvation and insulin injection. One sequential program comprised 2 hypoglycemic episodes during 4 days. The isolated hearts were subjected to 20-min ischemia/30-min reperfusion. The infarct size was larger in hearts with GF than those with sustained hyperglycemia. Activities of catalase and superoxide dismutase were decreased, and expressions of NADPH oxidase and thioredoxin-interacting protein were upregulated by GF accompanied by an increase of reactive oxygen species (ROS). Swollen mitochondria with destroyed cristae were observed in diabetic hearts; they were further devastated by GF. Microarray analysis revealed that the expressions of microRNA (miRNA)-200c and miRNA-141 were abundant in those hearts with GF. Overexpression of miRNA-200c and miRNA-141 decreased mitochondrial superoxide dismutase and catalase activities, and increased ROS levels. Meanwhile, knockdown of miRNA-200c and miRNA-141 significantly decreased ROS levels in cardiomyocytes exposed to GF. Conclusions GF increased ROS generation and enhanced ischemia/reperfusion injury in the diabetic heart. Upregulated miRNA-200c and miRNA-141 may account for the increased ROS.

A powerful technique for the concentration of rhodium (Rh) in plating wastewater was developed. The technique entails complexing Rh with 1-(2-pyridylazo)-2-naphthol (PAN) followed by homogeneous liquid–liquid extraction (HoLLE) with Zonyl FSA. The optimum HoLLE conditions were determined as follows: [ethanol]T = 30.0 vol.%, pH = 4.00, and Rh:PAN = 1:5. Under these optimum conditions, 88.1% of Rh was extracted into the sedimented liquid phase. After phase separation, the volume ratio [aqueous phase (Va) /sedimented liquid phase (Vs)] of Va and Vs was 1000 (50 mL → 0.050 mL). We then applied the new method to wastewater generated by the plating industry. The phase separation was satisfactorily achieved when the volume was scaled up to 1000 mL of the actual wastewater; 84.7% of Rh was extracted into the sedimented liquid phase. After phase separation, Va/Vs was 588 (1000 mL - 1.70 mL).