Yusuke Katayama

C-Terminal Tails of Sulfonylurea Receptors Control ADP-Induced Activation and Diazoxide Modulation of ATP-Sensitive K+ Channels

The ATP-sensitive K+ (KATP) channels are composed of the pore-forming K+ channel Kir6.0 and different sulfonylurea receptors (SURs). SUR1, SUR2A, and SUR2B are sulfonylurea receptors that are characteristic for pancreatic, cardiac, and vascular smooth muscle–type KATP channels, respectively. The structural elements of SURs that are responsible for their different characteristics have not been entirely determined. Here we report that the 42 amino acid segment at the C-terminal tail of SURs plays a critical role in the differential activation of different SUR-KATP channels by ADP and diazoxide. In inside-out patches of human embryonic kidney 293T cells coexpressing distinct SURs and Kir6.2, much higher concentrations of ADP were needed to activate channels that contained SUR2A than SUR1 or SUR2B. In all types of KATP channels, diazoxide increased potency but not efficacy of ADP to evoke channel activation. Replacement of the C-terminal segment of SUR1 with that of SUR2A inhibited ADP-mediated channel activation and reduced diazoxide modulation. Point mutations of the second nucleotide-binding domains (NBD2) of SUR1 and SUR2B, which would prevent ADP binding or ATP hydrolysis, showed similar effects. It is therefore suggested that the C-terminal segment of SUR2A possesses an inhibitory effect on NBD2-mediated ADP-induced channel activation, which underlies the differential effects of ADP and diazoxide on KATP channels containing different SURs.

Epidemiology and outcome of adult out-of-hospital cardiac arrest of non-cardiac origin in Osaka: a population-based study

Objectives To evaluate epidemiological characteristics of out-of-hospital cardiac arrests (OHCAs) by detailed non-cardiac cause and factors associated with the outcomes after OHCAs of non-cardiac origin. Design A prospective, population-based observational study. Setting The Utstein Osaka Project. Participants 14 164 adult patients aged ≥20 years old with OHCAs due to non-cardiac origin who were resuscitated by emergency-medical-service personnel or bystanders, and then were transported to medical institutions from January 2005 to December 2011. Primary outcome measures One-month survival after OHCA. Multiple logistic regression analysis was used to assess factors that were potentially associated with the outcome. Results During the study period, the 1-month survival rate was 5.3% (755/14 164). The proportion of 1-month survival was 6.2% (510/8239) in external causes, 6.5% (94/1148) in respiratory diseases, 0.8% (11/1309) in malignant tumours, 4.9% (55/1114) in strokes and 4.1% (85/2054) in others. As for external causes, the proportion of 1-month survival was 14.3% (382/2670) in asphyxia, 4.2% (84/1999) in hanging, 0.7% (9/1300) in fall, 1.1% (12/1062) in drowning, 1.6% (12/765) in traffic injury, 3.7% (7/187) in drug overuse and 1.6% (4/256) in unclassified external causes. In a multivariate analysis, adults aged <65 years old with arrests witnessed by bystanders, with normal activities of daily living before the arrests, having ventricular fibrillation arrests, having arrests in public places, intravenous fluid levels and early Emergency Medical Service response time were significant predictors for 1-month outcome after OHCAs of non-cardiac origin. The proportion of 1-month survival of all OHCAs of non-cardiac origin did not significantly increase (from 4.3% (86/2023) in 2005 to 4.9% (105/2126) in 2011) and the adjusted OR for one-increment of year was 1.01 (95% CI 0.97 to 1.06). Conclusions From a large OHCA registry in Osaka, we demonstrated that 1-month survival after OHCAs of non-cardiac origin was poor and stable.

Epinastine, a nonsedating histamine H1 receptor antagonist, has a negligible effect on HERG channel

Terfenadine and astemizole rarely cause cardiac arrhythmias by suppressing the cardiac rapid delayed rectifier K+ channel encoded by the human ether-a-go-go-related gene (HERG). Epinastine, however, has not been reported to have the adverse effect. We have therefore compared the effects of epinastine, terfenadine and astemizole on HERG channels expressed in Xenopus oocytes. Terfenadine and astemizole suppressed the HERG current with IC50 of 431 nM and 69 nM, respectively. In contrast, 100 microM epinastine inhibited the HERG current by only 11+/-2.1%. These results may provide an explanation for the difference in the cardiotoxicity between different nonsedating histamine H1 receptor antagonists.

Characteristics and Outcomes of Bath-Related Out-of-Hospital Cardiac Arrest in Japan

BACKGROUND Characteristics and outcomes of emergency patients with bath-related sudden cardiac arrest in prehospital settings have not been sufficiently investigated. METHODSANDRESULTS From a prospective population-based registry, which covers all out-of-hospital cardiac arrests (OHCAs) in Osaka City, a total of 642 patients who had a bath-related OHCA from 2012 to 2014 were enrolled in the analyses. The characteristics and outcomes of OHCA were compared by three locations of arrest: home baths (n=512), public baths (n=102), and baths in other public institutions (n=28). Overall, bath-related OHCAs mainly occurred in winter (December-February, 48.9%, 314/642). The proportion of OHCAs that were witnessed by bystanders was 6.4% (33/512) in home baths, 17.6% (18/102) in public baths, and 25.0% (7/28) in baths in other public institutions. The proportion of public-access automated external defibrillator pad application was 0.8% (4/512) in home baths, 6.9% (7/102) in public baths, and 50.0% (14/28) in baths in other public institutions. Only 1 survivor with a favorable neurologic outcome was observed in a home bath, whereas there were no patients who survived with favorable neurologic outcomes in public baths and baths in other public institutions. CONCLUSIONS Bath-related OHCAs mainly occurred in winter, and the outcome of victims was exceedingly poor, irrespective of location of arrest. The establishment of preventive measures as well as earlier recognition of cardiac arrest by bystanders are needed. (Circ J 2016; 80: 1564-1570).

Factors associated with the difficulty in hospital acceptance at the scene by emergency medical service personnel: a population-based study in Osaka City, Japan

Objectives To investigate the association between the difficulty in hospital acceptance at the scene by emergency medical service (EMS) personnel and prehospital demographic factors and reasons for EMS calls. Design A retrospective, observational study. Setting Osaka City, Japan. Participants A total of 100 649 patients transported to medical institutions by EMS from January 2013 to December 2013. Primary outcome measurements The definition of difficulty in hospital acceptance at the scene was EMS personnel making ≥5 phone calls to medical institutions until a decision to transport was determined. Multivariable analysis was used to assess the relationship between difficulty in hospital acceptance and prehospital factors and reasons for EMS calls. Results Multivariable analysis showed the elderly, foreigners, loss of consciousness, holiday/weekend, and night-time to be positively associated with difficulty in hospital acceptance at the scene. As reasons for EMS calls, gas poisoning (adjusted OR 3.281, 95% CI 1.201 to 8.965), trauma by assault (adjusted OR 2.662, 95% CI 2.390 to 2.966), self-induced drug abuse/gas poisoning (adjusted OR 4.527, 95% CI 3.921 to 5.228) and self-induced trauma (adjusted OR 1.708, 95% CI 1.369 to 2.130) were positively associated with the difficulty in hospital acceptance at the scene. Conclusions Ambulance records in Osaka City showed that certain prehospital factors such as night-time were positively associated with difficulty in hospital acceptance at the scene, and reasons for EMS calls, such as self-induced drug abuse/gas poisoning, were also positive predictors for difficulty in hospital acceptance at the scene.

Influence of arterial stiffness on cardiovascular outcome in patients without high blood pressure

Objective Although blood pressure (BP) is a major determinant of arterial stiffness, whether high pulse wave velocity (PWV) adversely influences cardiac parameters and cardiovascular (CV) outcome in patients without high BP remains unclear. Methods Outpatients without high BP (n=320), defined as systolic BP ≥140 mm Hg, were enrolled in this retrospective study. At baseline, all patients underwent echocardiography and multidetector CT to determine the coronary artery calcification (CAC) score. Arterial stiffness was assessed based on brachial-ankle PWV (baPWV), from which patients were classified into two groups: those with high (≥18 m/s, n=89) and low baPWV (<18 m/s, n=231). Cardiac parameters and CV event incidence during the follow-up period were compared between these groups. Results In multivariable linear regression analysis, baPWV was significantly associated with CAC score and serum N-terminal pro-brain natriuretic peptide hormone level, after adjustment for confounding factors. In multivariable logistic regression analysis, baPWV ≥18 m/s was significantly associated with CAC score ≥400 (OR 2.466, 95% CI 1.012 to 6.009, p=0.0471). Kaplan-Meier analysis showed that the high-baPWV group experienced more CV events during the 575 days of follow-up (20% vs 6%, p=0.0003). Conclusions High baPWV was associated with greater CAC and a high risk of a future CV event, especially coronary artery disease, even in patients without high BP.

Evaluation of factors associated with the difficulty in finding receiving hospitals for traffic accident patients at the scene treated by emergency medical services: a population-based study in Osaka City, Japan

Although the prolongation of the time between injury and hospital arrival of traffic accident patients can influence their prognosis, factors associated with the difficulty in hospital acceptance of these patients have not been sufficiently evaluated in Japan.

An increase in the coronary calcification score is associated with an increased risk of heart failure in patients without a history of coronary artery disease

BACKGROUND The presence of coronary artery calcification (CAC) and its severity predict future cardiovascular events and is used for risk stratification. However, the association of CAC with heart failure (HF) in patients without a history of coronary artery disease (CAD) remains unclear. This study aimed to determine the correlations of CAC with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and HF events in patients without a history of CAD or HF. METHODS From June 2010 to June 2013, a total of 487 patients without a history of CAD and HF were enrolled. All of the patients underwent plane multi-detector computed tomography. They were divided into four categories according to CAC scores: ≤10, 11-100, 101-400, and ≥401. RESULTS The proportion of patients with high NT-proBNP levels increased with CAC categories (p<0.0001). The CAC score was associated with NT-proBNP levels ≥400pg/ml, with an odds ratio of 2.901 (95% confidence interval: 1.368-6.151, p=0.0055) for CAC scores ≥401 compared with CAC scores of 0-10 after adjustment for confounding factors. During the follow-up period of 497±315 days, nine patients were admitted for HF. Kaplan-Meier analysis showed that patients with CAC scores ≥401 had a lower rate of freedom from admission for HF with cumulative incidences of 0.4%, 1%, 2%, and 8% for CAC scores of 0-10, 11-100, 101-400, and ≥401, respectively (p<0.0001). Increasing CAC scores were associated with an increase in incidence of admission for HF, with a hazard ratio of 10.371 for CAC scores ≥401 (95% CI: 1.062-101.309, p=0.0443) compared with CAC scores of 0-10 after adjustment for risk factors. CONCLUSION Severe CAC is an independent determinant of high NT-proBNP levels and a predictor of admission for HF in a population without a history of CAD or HF.

High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.

BACKGROUND The number of people living in high-rise buildings has recently been increasing in Japan, and delayed transport time by emergency-medical-service (EMS) personnel from higher floors could lead to lower survival after out-of-hospital cardiac arrest (OHCA). However, there are no clinical studies assessing the association between the floor where patients reside and neurologically favorable outcome after OHCA. METHODS This was a prospective, population-based study conducted in Osaka City, Japan that enrolled adults aged >=18years suffering an OHCA of cardiac origin before EMS arrival between 2013 and 2014. The primary outcome measure was one-month survival with neurologically favorable outcome. We divided OHCA patients into the following groups: those residing on >=3 floors (the high floor group) and <3 floors (the low floor group). Multiple logistic regression analysis was used to assess factors associated with neurologically favorable outcome. RESULTS A total of 2979 patients were eligible for analysis. Of them, 1885 (62.3%) occurred below the third floor and 1094 (37.4%) occurred at or above the third floor. The proportion of neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (2.7% [30/1094] versus 4.8% [91/1885], P=0.005). In a multivariate analysis, neurologically favorable outcome after OHCA was significantly lower in the high floor group than in the low floor group (adjusted odds ratio, 0.59 [95% confidence interval, 0.37-0.96]). CONCLUSIONS In this population, one-month survival with neurologically favorable outcome from OHCA was lower in the high floor group than in the low floor group.

Improvements in Patient Acceptance by Hospitals Following the Introduction of a Smartphone App for the Emergency Medical Service System: A Population-Based Before-and-After Observational Study in Osaka City, Japan

Background Recently, the number of ambulance dispatches has been increasing in Japan, and it is therefore difficult for hospitals to accept emergency patients smoothly and appropriately because of the limited hospital capacity. To facilitate the process of requesting patient transport and hospital acceptance, an emergency information system using information technology (IT) has been built and introduced in various communities. However, its effectiveness has not been thoroughly revealed. We introduced a smartphone app system in 2013 that enables emergency medical service (EMS) personnel to share information among themselves regarding on-scene ambulances and the hospital situation. Objective The aim of this study was to assess the effects of introducing this smartphone app on the EMS system in Osaka City, Japan. Methods This retrospective study analyzed the population-based ambulance records of Osaka Municipal Fire Department. The study period was 6 years, from January 1, 2010 to December 31, 2015. We enrolled emergency patients for whom on-scene EMS personnel conducted hospital selection. The main endpoint was the difficulty experienced in gaining hospital acceptance at the scene. The definition of difficulty was making ≥5 phone calls by EMS personnel at the scene to hospitals until a decision to transport was determined. The smartphone app was introduced in January 2013, and we compared the patients treated from 2010 to 2012 (control group) with those treated from 2013 to 2015 (smartphone app group) using an interrupted time-series analysis to assess the effects of introducing this smartphone app. Results A total of 600,526 emergency patients for whom EMS personnel selected hospitals were eligible for our analysis. There were 300,131 emergency patients in the control group (50.00%, 300,313/600,526) from 2010 to 2012 and 300,395 emergency patients in the smartphone app group (50.00%, 300,395/600,526) from 2013 to 2015. The rate of difficulty in hospital acceptance was 14.19% (42,585/300,131) in the control group and 10.93% (32,819/300,395) in the smartphone app group. No change over time in the number of difficulties in hospital acceptance was found before the introduction of the smartphone app (regression coefficient: −2.43, 95% CI −5.49 to 0.64), but after its introduction, the number of difficulties in hospital acceptance gradually decreased by month (regression coefficient: −11.61, 95% CI −14.57 to −8.65). Conclusions Sharing information between an ambulance and a hospital by using the smartphone app at the scene was associated with decreased difficulty in obtaining hospital acceptance. Our app and findings may be worth considering in other areas of the world where emergency medical information systems with IT are needed.