A novel ryanodine receptor 2 inhibitor, M201-A, enhances natriuresis, renal function and lusi-inotropic actions: Preclinical and phase I study.

BACKGROUND AND PURPOSE: The ryanodine receptor 2 (RyR2) is present in both the heart and kidneys, and plays a crucial role in maintaining intracellular Ca2+ homeostasis in cells in these organs. This study aimed to investigate the impact of M201-A on RyR2, as well as studying its effects on cardiac and renal functions in preclinical and clinical studies. EXPERIMENTAL APPROACH: Following the administration of M201-A (1,4-benzothiazepine-1-oxide derivative), we monitored diastolic Ca2+ leak via RyR2 and intracellular Ca2+ concentration in isolated rat cardiomyocytes and in cardiac and renal function in animals. In a clinical study, M201-A was administered intravenously at doses of 0.2 and 0.4 mg·kg-1 once daily for 20 min for four consecutive days in healthy males, with the assessment of haemodynamic responses. KEY RESULTS: In rat heart cells, M201-A effectively inhibited spontaneous diastolic Ca2+ leakage through RyR2 and exhibited positive lusi-inotropic effects on the rat heart. Additionally, it enhanced natriuresis and improved renal function in dogs. In human clinical studies, when administered intravenously, M201-A demonstrated an increase in natriuresis, glomerular filtration rate and creatinine clearance, while maintaining acceptable levels of drug safety and tolerability. CONCLUSIONS AND IMPLICATIONS: The novel drug M201-A inhibited diastolic Ca2+ leak via RyR2, improved cardiac lusi-inotropic effects in rats, and enhanced natriuresis and renal function in humans. These findings suggest that this drug may offer a potential new treatment option for chronic kidney disease and heart failure.

Association between neuromuscular blocking agent use and outcomes among out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and target temperature management: A secondary analysis of the SAVE-J II study.

Background: Neuromuscular blocking agents are used to control shivering in cardiac arrest patients treated with target temperature management. However, their effect on outcomes in patients treated with extracorporeal cardiopulmonary resuscitation is unclear. Methods: This study was a secondary analysis of the SAVE-J II study, a retrospective multicenter study of 2175 out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation in Japan. We classified patients into those who received neuromuscular blocking agents and those who did not and compared in-hospital mortality and incidence rates of favorable neurological outcome and in-hospital pneumonia between the groups using multivariable regression models and stabilized inverse probability weighting with propensity scores. Results: Six hundred sixty patients from the SAVE-J II registry were analyzed. Neuromuscular blocking agents were used in 451 patients (68.3%). After adjusting for potential confounders, neuromuscular blocking agents use was not significantly associated with in-hospital mortality (aHR 0.88; 95% CI, 0.67-1.14), favorable neurological outcome (aOR 0.85; 95% CI, 0.60-1.11), or pneumonia (aOR 1.52; 95% CI, 0.85-2.71). The results for in-hospital mortality (aHR 0.89; 95% CI, 0.64-1.25), favorable neurological outcome (aOR 0.94; 95% CI, 0.59-1.48) and pneumonia (aOR 1.59; 95% CI, 0.74-3.41) were similar after weighting was performed. Conclusions: Although data on the rationale for using neuromuscular blocking agents were unavailable, their use was not significantly associated with outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and targeted temperature management. Neuromuscular blocking agents should be used based on individual clinical indications.

Development, implementation, and refinement of a comprehensive postcardiac arrest care training course in Japan.

Aim: In Japan, no training course is dedicated to postcardiac arrest care (PCAC), including venoarterial extracorporeal membrane oxygenation (VA-ECMO); thus, faculty members of the Japanese Circulation Society developed an original, comprehensive PCAC training course. This report reviews the development, implementation, and refinement of this PCAC training course. Methods: We examined the preserved data from the Japanese Circulation Society PCAC training courses between 2014 and 2020. Data related to the learning content and number of the attendees and instructors were collected and summarized. Results: Sixteen courses were held between August 2014 and February 2020, before the coronavirus disease 2019 (COVID-19) pandemic. A total of 677 health care providers participated: 351 doctors, 225 nurses, 62 perfusionists, five emergency medical professionals, and two pharmacists. Thirty-two attendees' data were missing. The core learning contents of all the courses included a standardized postcardiac arrest algorithm, targeted temperature management, VA-ECMO cannulation skills, and postcannulation management. Concerning curriculum evolution, extracorporeal cardiopulmonary resuscitation simulation, postarrest neurological examination and monitoring, and ultrasound-guided Seldinger technique training were added in the 4th, 5th, and 13th courses, respectively. Conclusion: The Japanese Circulation Society PCAC training course has been developed and refined to provide an organized, comprehensive opportunity for health care providers to acquire specific knowledge and skills in PCAC and VA-ECMO.

Prehospital Administration of Aspirin and Nitroglycerin for Patients With Suspected Acute Coronary Syndrome　- A Systematic Review.

Background: Recent guidelines for acute coronary syndrome (ACS) recommend prehospital administration of aspirin and nitroglycerin for ACS patients. However, there is no clear evidence to support this. We investigated the benefits and harms of prehospital administration of aspirin and nitroglycerin by non-physician healthcare professionals in patients with suspected ACS. Methods and Results: We searched the PubMed database and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Three retrospective studies for aspirin and 1 for nitroglycerin administered in the prehospital setting to patients with acute myocardial infarction were included. Prehospital aspirin administration was associated with significantly lower 30-day and 1-year mortality compared with aspirin administration after arrival at hospital, with odds ratios (OR) of 0.59 (95% confidence interval [CI] 0.35-0.99) and 0.47 (95% CI 0.36-0.62), respectively. Prehospital nitroglycerin administration was also associated with significantly lower 30-day and 1-year mortality compared with no prehospital administration (OR 0.34 [95% CI 0.24-0.50] and 0.38 [95% CI 0.29-0.50], respectively). The certainty of evidence was very low in both systematic reviews. Conclusions: Our systematic reviews suggest that prehospital administration of aspirin and nitroglycerin by non-physician healthcare professionals is beneficial for patients with suspected ACS, although the certainty of evidence is very low. Further investigation is needed to determine the benefit of the prehospital administration of these agents.

Prehospital Activation of the Catheterization Laboratory Among Patients With Suspected ST-Elevation Myocardial Infarction Outside of a Hospital　- Systematic Review and Meta-Analysis.

Background: In the management of patients with ST-elevation myocardial infarction (STEMI), system delays for reperfusion therapy are still a matter of concern. We investigated the impact of prehospital activation of the catheterization laboratory in the management of STEMI patients. Methods and Results: This is a systematic review of observational studies. A search was conducted of the PubMed database from inception to July 2020 to identify articles for inclusion in the study. The critical outcomes were short- and long-term mortality. The important outcome was door-to-balloon time. The GRADE approach was used to assess the certainty of the evidence. Seven studies assessed short-term mortality; 1,541 were assigned to the prehospital activation (PH) group and 1,191 were assigned to the emergency department activation (ED) group. There were 26 fewer deaths per 1,000 patients in the PH group. Three studies assessed long-term mortality; 713 patients were assigned to the PH group and 1,026 were assigned to the ED group. There were 54 fewer deaths per 1,000 patients among the PH group. Five studies assessed door-to-balloon time; 959 were assigned to the PH group and 631 to the ED group. Door-to-balloon time was 33.1 min shorter in the PH group. Conclusions: Prehospital activation of the catheterization laboratory resulted in lower mortality and shorter door-to-balloon time for patients with suspected STEMI outside of a hospital.

Supplemental Oxygen and Acute Myocardial Infarction　- A Systematic Review and Meta-Analysis.

Background: In Japan, oxygen is commonly administered during the acute phase of myocardial infarction (MI) to patients without oxygen saturation monitoring. In this study we assessed the effects of supplemental oxygen therapy, compared with ambient air, on mortality and cardiac events by synthesizing evidence from randomized controlled trials (RCTs) of patients with suspected or confirmed acute MI. Methods and Results: PubMed was systematically searched for full-text RCTs published in English before June 21, 2020. Two reviewers independently screened the search results and appraised the risk of bias. The estimates for each outcome were pooled using a random-effects model. In all, 2,086 studies retrieved from PubMed were screened. Finally, 7,322 patients from 9 studies derived from 4 RCTs were analyzed. In-hospital mortality in the oxygen and ambient air groups was 1.8% and 1.6%, respectively (risk ratio [RR] 0.90; 95% confidence interval [CI] 0.38-2.10]); 0.8% and 0.5% of patients, respectively, experienced recurrent MI (RR 0.44; 95% CI 0.12-1.54), 1.5% and 1.6% of patients, respectively, experienced cardiac shock (RR 1.10; 95% CI 0.77-1.59]), and 2.4% and 2.0% of patients, respectively, experienced cardiac arrest (RR 0.91; 95% CI 0.43-1.94). Conclusions: Routine supplemental oxygen administration may not be beneficial or harmful, and high-flow oxygen may be unnecessary in normoxic patients in the acute phase of MI.

Systematic Review and Meta-Analysis of Diagnostic Accuracy to Identify ST-Segment Elevation Myocardial Infarction on Interpretations of Prehospital Electrocardiograms.

Background: The aim of this study was to assess and discuss the diagnostic accuracy of prehospital ECG interpretation through systematic review and meta-analyses. Methods and Results: Relevant literature published up to July 2020 was identified using PubMed. All human studies of prehospital adult patients suspected of ST-segment elevation myocardial infarction in which prehospital electrocardiogram (ECG) interpretation by paramedics or computers was evaluated and reporting all 4 (true-positive, false-positive, false-negative, and true-negative) values were included. Meta-analyses were conducted separately for the diagnostic accuracy of prehospital ECG interpretation by paramedics (Clinical Question [CQ] 1) and computers (CQ2). After screening, 4 studies for CQ1 and 6 studies for CQ2 were finally included in the meta-analysis. Regarding CQ1, the pooled sensitivity and specificity were 95.5% (95% confidence interval [CI] 82.5-99.0%) and 95.8% (95% CI 82.3-99.1%), respectively. Regarding CQ2, the pooled sensitivity and specificity were 85.4% (95% CI 74.1-92.3%) and 95.4% (95% CI 87.3-98.4%), respectively. Conclusions: This meta-analysis suggests that the diagnostic accuracy of paramedic prehospital ECG interpretations is favorable, with high pooled sensitivity and specificity, with an acceptable estimated number of false positives and false negatives. Computer-assisted ECG interpretation showed high pooled specificity with an acceptable estimated number of false positives, whereas the pooled sensitivity was relatively low.

Performance of the 0-Hour/1-Hour Algorithm for Diagnosing Myocardial Infarction in Patients With Chest Pain in the Emergency Department　- A Systematic Review and Meta-Analysis.

Background: This study assessed the diagnostic performance of the 0-hour/1-hour (0/1-h) algorithm to rule in and rule out acute myocardial infarction (MI) in patients presenting to the emergency department (ED) for suspected acute coronary syndrome without ST-segment elevation, as recommended in the 2015 European Society of Cardiology (ESC) guideline. Methods and Results: Following the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy (PRISMA-DTA) guidelines, a systematic review was conducted using the PubMed database from inception to March 31, 2020. We included any article published in English investigating the diagnostic performance of the ESC 0/1-h algorithm for diagnosing MI in patients with chest pain visiting the ED. Of 651 studies identified as potentially available for the study, 7 studies including 16 databases were analyzed. A meta-analysis of the diagnostic accuracy of the 0/1-h algorithm using high-sensitivity cardiac troponin I (hs-cTn) with 6 observational databases showed a pooled sensitivity of 99.3% (95% confidence interval [CI] 98.5-99.7%) and a pooled specificity of 90.1% (95% CI 80.7-95.2%). A meta-analysis of the diagnostic accuracy of 10 observational databases of the ESC 0/1-h algorithm using hs-cTn revealed a pooled sensitivity of 99.3% (95% CI 96.9-99.9%) and a pooled specificity of 91.7% (95% CI 83.5-96.1%). Conclusions: Our results demonstrate that the ESC 0/1-h algorithm can effectively rule in and rule out patients with non-ST-segment elevation MI.

Impact of Prehospital 12-Lead Electrocardiography and Destination Hospital Notification on Mortality in Patients With Chest Pain　- A Systematic Review.

Background: To achieve early reperfusion therapy for ST-elevation myocardial infarction (STEMI), proper and prompt patient transportation and activation of the catheterization laboratory are required. We investigated the efficacy of prehospital 12-lead electrocardiogram (ECG) acquisition and destination hospital notification in patients with STEMI. Methods and Results: This is a systematic review of observational studies. We searched the PubMed database from inception to March 2020. Two reviewers independently performed literature selection. The critical outcome was short-term mortality. The important outcome was door-to-balloon (D2B) time. We used the GRADE approach to assess the certainty of the evidence. For the critical outcome, 14 studies with 29,365 patients were included in the meta-analysis. Short-term mortality was significantly lower in the group with prehospital 12-lead ECG acquisition and destination hospital notification than in the control group (odds ratio 0.72; 95% confidence interval [CI] 0.61-0.85; P<0.0001). For the important outcome, 10 studies with 2,947 patients were included in the meta-analysis. D2B time was significantly shorter in the group with prehospital 12-lead ECG acquisition and destination hospital notification than in the control group (mean difference -26.24; 95% CI -33.46, -19.02; P<0.0001). Conclusions: Prehospital 12-lead ECG acquisition and destination hospital notification is associated with lower short-term mortality and shorter D2B time than no ECG acquisition or no notification among patients with suspected STEMI outside of a hospital.

Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan.

BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

Effects of Door-In to Door-Out Time on Mortality Among ST-Segment Elevation Myocardial Infarction Patients Transferred for Primary Percutaneous Coronary Intervention　- Systematic Review and Meta-Analysis.

Background: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is now widely accepted. Recent guidelines have focused on total ischemic time, because shorter total ischemic time is associated with a more favorable prognosis. The door-in to door-out (DIDO) time, defined as time from arrival at a non-PCI-capable hospital to leaving for a PCI-capable hospital, may affect STEMI patient prognosis. However, a relevant meta-analysis is lacking. Methods and Results: We searched PubMed for clinical studies comparing short-term (30-day and in-hospital) mortality rates of STEMI patients undergoing primary PCI with DIDO times of ≤30 vs. >30 min. Two investigators independently screened the search results and extracted the data. Random effects estimators with weights calculated by the inverse variance method were used to determine pooled risk ratios. The search retrieved 1,260 studies; of these, 2 retrospective cohort studies (15,596 patients) were analyzed. In the DIDO time ≤30 and >30 min groups, the primary endpoint (i.e., in-hospital or 30-day mortality) occurred for 51 of 1,794 (2.8%) and 831 of 13,802 (6.0%) patients, respectively. The incidence of the primary endpoint was significantly lower in the DIDO time ≤30 min group (odds ratio 0.45; 95% confidence interval 0.34-0.60). Conclusions: Our findings suggest that a DIDO time ≤30 min is associated with a lower short-term mortality rate. However, further larger systematic reviews and meta-analyses are needed to validate our findings.

Cluster Randomized Trial of Duration of Cooling in Targeted Temperature Management After Resuscitation for Cardiac Arrest.

Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12-24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1-2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12- to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67-1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72-1.14, P=0.387). Conclusions: TTM at 34℃ for 12-24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34℃ for 12-24 h for neurologic outcomes.

Variability of extracorporeal cardiopulmonary resuscitation practice in patients with out-of-hospital cardiac arrest from the emergency department to intensive care unit in Japan.

AIM: A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out-of-hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU). METHODS: An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE-J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra-aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded. RESULTS: We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two-thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume (P for trend <0.001). Intra-aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions. CONCLUSIONS: We described the variability in ECPR practice in patients with OHCA from the ED to the ICU.

Theophylline-Induced Left Ventricular Relaxation Disturbance in Magnesium-Deficient Rats: Improvement by K201, a Novel 1,4-Benzothiazepine Derivative.

BACKGROUND: Although magnesium deficiency induces left ventricular dysfunction, it is not known whether both systolic and diastolic functions are altered to the same extent. In this study, we investigated the effects of theophylline on left ventricular function in rats fed a normal diet or a magnesium-deficient diet for 1 month, and determined whether K201, a multi-channel blocker, modulated the effects of theophylline. METHODS: Theophylline was infused at 5 mg/kg/min for 15 min in 6 control rats and 6 magnesium-deficient rats, and hemodynamic measurements were performed. In another 6 magnesium-deficient rats, K201 was infused at 0.1 mg/kg/min for 15 min simultaneously with theophylline. RESULTS: Theophylline induced persistent increases in heart rate, peak positive first derivative of left ventricular pressure (+dP/dt), and a transient increase in left ventricular end-diastolic pressure (LVEDP), but did not affect left ventricular systolic pressure (LVSP) and peak negative first derivative of left ventricular pressure (-dP/dt) in the control rats. In contrast, in the magnesium-deficient rats, there was a persistent decrease in LVSP and a persistent increase in -dP/dt after theophylline infusion, although increases in heart rate, +dP/dt and LVEDP were similar to those in the control rats. When K201 was infused along with theophylline in the magnesium-deficient rats, both the decrease in LVSP and increase in -dP/dt were suppressed. CONCLUSIONS: Theophylline impaired left ventricular function in the magnesium-deficient rats, and this was improved by K201. K201 may provide new insights regarding future strategies for heart failure treatment.

Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: A report from the Angina Pectoris-Myocardial Infarction Multicenter Investigators in Japan.

BACKGROUND: We sought to compare the prognosis of patients with spontaneous coronary artery dissection (SCAD) and atherosclerosis as the cause of acute myocardial infarction (AMI), especially in young females. METHODS AND RESULTS: A total of 20,195 patients with AMI at 20 institutions between 2000 and 2013 were retrospectively studied. Major adverse cardiac event (MACE: cardiac death, AMI or urgent revascularization) was the endpoint. The overall prevalence of SCAD was 0.31% (n=63; female, 94%). SCAD developed following emotional stress in 29% of patients. Revascularization was performed in 56% (35 of 63 patients), and SCAD recurrence developed in the originally involved vessel in 6 of 35 patients with revascularization, compared to none among 28 patients after conservative therapy (p=0.002). We compared the clinical characteristics of young female AMI patients aged ≤50years in the SCAD (n=45) and no-SCAD groups (atherosclerotic AMI, n=55). During a median follow-up of 50months, SCAD recurred in 27% of patients, of which 42% was in the first 30days. Kaplan-Meier analysis showed a significantly higher incidence of MACE in the SCAD group compared to the no-SCAD group (hazard ratio, 6.91; 95% confidence interval, 2.5 to 24.3; p<0.001), although the rate of successful percutaneous coronary intervention for SCAD was as high as 92%. CONCLUSIONS: Young female patients with SCAD represent a high-risk subgroup of patients with AMI and require close follow-up.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study.

AIM: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Impact of irbesartan, an angiotensin receptor blocker, on uric acid level and oxidative stress in high-risk hypertension patients.

Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients' prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6 mg ml(-1), P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65 U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress.