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Hosoda H.,Japan National Cardiovascular Center Research Institute
Methods in enzymology | Year: 2012

Octanoyl modification of ghrelin is rapidly hydrolyzed to des-acyl ghrelin in blood samples. Owing to the increased interest in ghrelin measurement, a standardized method of sample collection is required. This chapter investigates the effect of a variety of anticoagulants and storage conditions on ghrelin stability. Experiment 1 evaluates the effects of anticoagulants on ghrelin measurements. Experiment 2 evaluates the effect of plasma pH on ghrelin stability. Experiment 3 evaluates the mechanisms of degradation of the active form of ghrelin in plasma. Experiment 4 investigates the kinetics of ghrelin following intravenous injection of rat ghrelin. In whole blood and plasma, octanoylated ghrelin is highly unstable. The collection of blood samples with EDTA-aprotinin under cooled conditions was appropriate to maintain ghrelin stability. Acidification of plasma to pH 3-4 and storage at 4°C maintained ghrelin stability. The degradation of ghrelin was shown to be due to the hydrolysis to des-acyl ghrelin. After intravenous administration to rats, plasma ghrelin levels rapidly decreased with a half-life of 8 min. The results showed that the ghrelin values measured in human blood samples were markedly affected by the conditions of collection and storage, the pH, and the RIA method in measurement. Measuring the ghrelin values of the active form is useful for studying plasma ghrelin changes over short time periods. As ghrelin is highly unstable, it is necessary to standardize the preparation of samples to ensure reliable ghrelin measurements. Copyright © 2012 Elsevier Inc. All rights reserved.

Ogo T.,Japan National Cardiovascular Center Research Institute
Current Opinion in Pulmonary Medicine | Year: 2015

Purpose of review Chronic thromboembolic pulmonary hypertension (CTEPH), especially when severe in patients unsuited for pulmonary endarterectomy, has a poor prognosis. Balloon pulmonary angioplasty (BPA) is a new catheterbased alternative treatment option for patients with inoperable CTEPH. BPA has not been widely accepted, however, primarily because of possible fatal complications, although effects described in 2001 were encouraging. Recent studies about BPA from Japan and Norway are promising. However, this emerging catheter-based intervention is still considered to be experimental because of a number of concerns and unanswered questions. This review describes the recent progress in BPA at the dawn of a new CTEPH treatment era. Recent findings Recent studies about BPA show consistently beneficial effects in haemodynamics, symptoms, 6-minute walking distance, and biomarkers. Exercise capacity and right ventricular function are also improved by BPA. However, this new technique still has potentially fatal complications, including reperfusion oedema and pulmonary artery perforation, even in recent studies. There remain a number of concerns and unanswered questions about BPA, including indications, best procedural approach, and long-term outcomes. Summary Recent advances in BPA for inoperable CTEPH are promising. Further investigation by multidisciplinary CTEPH teams is mandatory before BPA's role in CTEPH treatment strategies is determined. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Yamamoto K.,Tottori University | Origasa H.,University of Toyama | Hori M.,Japan National Cardiovascular Center Research Institute
European Journal of Heart Failure | Year: 2013

Aims: The therapeutic strategy for heart failure with preserved ejection fraction (HFPEF) has not been established. The Japanese Diastolic Heart Failure Study (J-DHF) is a multicentre, prospective, randomized, open, blinded-endpoint trial, designed to assess the effects of carvedilol in HFPEF patients.Methods and resultsA total of 245 patients with heart failure and ejection fraction >40% were randomly assigned into those treated with (carvedilol group, n = 120) and without carvedilol (control group, n = 125). The primary outcome is a composite of cardiovascular death and unplanned hospitalization for heart failure. During a median follow-up of 3.2 years, the primary endpoint occurred in 29 patients in the carvedilol group and in 34 patients in the control group [adjusted hazard ratio (HR) 0.902, 95% confidence interval (CI) 0.546-1.488, P = 0.6854]. Another major composite endpoint, cardiovascular death and unplanned hospitalization for any cardiovascular causes, occurred in 38 patients of the carvedilol group and 52 patients of the control group (HR 0.768, 95% CI 0.504-1.169; P = 0.2178). The target dose of carvedilol was 20 mg/day, but the median prescribed dose was 7.5 mg/day. In the patients treated with standard doses (carvedilol >7.5 mg/day, n = 58), this composite outcome was significantly less than in the controls (HR 0.539, 95% CI 0.303-0.959; P = 0.0356), whereas it was comparable with the controls in the patients treated with carvedilol ≤7.5 mg/day (n = 62, HR 1.070, 95% CI 0.650-1.763; P = 0.7893).ConclusionsCarvedilol did not improve prognosis of HFPEF patients overall; however, the standard dose, not the low dose, prescription might be effective. This may facilitate further investigation.UMIN number: C000000318. © 2012 The Author.

Kokubo Y.,Japan National Cardiovascular Center Research Institute
Current Opinion in Neurology | Year: 2012

Purpose of review: Recently, many guidelines have given new evidence on the risk factors for stroke. In this review, I refer to the most important guidelines for primary prevention of stroke and hypertension, especially focused on diet and physical activity. Recent findings: The health behavior recommendations in recent guidelines for the primary prevention of stroke are virtually identical, and the same recommendations appear in the recent guidelines for the management of hypertension, especially with respect to diet and physical activity. The recommended health behaviors consist of weight reduction, reduction of salt intake, increase in fruit and vegetable intake, decrease in saturated and total fat intake (increase in fish intake), physical activity, and moderation of alcohol consumption. Fruits and vegetables have high levels of potassium, antioxidants, phytochemicals, and dietary fiber, and thus are also considered preventive of cardiovascular disease and its risk factors. It was found that individuals with many of these health behaviors have been shown to have a lowered risk of stroke. Summary: The health behaviors, especially those related to diet and physical activity, appearing in recent guidelines for the management of hypertension are also important for the primary prevention of stroke, and appear in recent stroke guidelines. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Kitamura S.,Japan National Cardiovascular Center Research Institute
Circulation Journal | Year: 2011

The internal thoracic artery (ITA) has become the gold standard graft material for modern coronary artery bypass grafting (CABG) because of its excellent long-term patency. The use of ITA grafts has also prolonged the postoperative survival of patients when applied to the left anterior descending artery or used bilaterally as 2 grafts for the left coronary system. Moreover, recent large-scale randomized clinical trials comparing the survival rates between CABG and percutaneous coronary intervention (PCI) with stents have shown that CABG is more effective for improving the survival of patients with severe coronary artery disease and/or in those with diabetes mellitus. The fundamental principle underlying these clinical benefits of CABG is the excellent endothelial function of the ITA, which provides physiological and metabolic effects that are beneficial not only for the graft itself, but also for the recipient coronary system. The production of nitric oxide and prostanoids by the ITA endothelium and their beneficial effects on the downstream coronary artery should therefore be taken into consideration when debating the merits of CABG vs. PCI.

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