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Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO2) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P

Among heart failure patients diagnosed as having exertional oscillatory ventilation (OV), some present with OV at rest that persists during exercise, and others develop OV only after the onset of exercise during cardiopulmonary exercise (CPX) testing. We tested whether or not there was any difference in the prognostic significance between the two abnormal breathing patterns.Patients with New York Heart Association class III-heart failure were categorized into the following 3 groups according to their ventilation pattern during the CPX: patients with an OV pattern at rest that persisted for ≥60% of the exercise test at an amplitude of ≥15% of the average resting value (group 1), patients with the same abnormal ventilatory pattern as group 1 that was observed only during exercise (group 2), and patients without any OV (group 3). The patients were followed-up for at least 2 years to assess the composite outcome of cardiac death or hospitalization for worsening heart failure.The occurrence of the composite outcome differed significantly across the groups with its highest occurrence in group 1 (21/29 [72.4%], 15/38 [39.5%] and 48/167 [28.7%]; log-rank P 0.001). In multivariate hazard analyses, an N-terminal pro-brain natriuretic peptide of900 pg/mL (hazard ratio [HR] = 1.72, P = 0.04), and group 1 (HR 2.03, P = 0.02) were independently associated with the composite outcome.Checking for the resting OV prior to incremental exercise during CPX testing may be helpful in risk-stratification among subjects with advanced heart failure.

Background Nearly half of patients with heart failure have normal left ventricular ejection fraction (LVEF), but their prognosis is no better than those with reduced LVEF. Although peak oxygen consumption (VO2) is an independent predictor of mortality in heart failure, it is unclear how cardiac function during exercise contributes to peak VO2. Therefore, we explored the useful parameters measured by exercise stress echocardiography to predict peak VO2 in patients with heart failure with preserved LVEF (HFpEF). Methods and Results We assessed 80 patients being investigated for effort intolerance or dyspnea and finally analyzed 50 patients who satisfied the HFpEF criteria. Mean peak VO2 was 16.4±2.8 mL/kg/min. Twenty-three patients (46.0%) achieved a peak VO2

Electrocardiographic left ventricular hypertrophy (ECG-LVH) gradually regressed after aortic valve replacement (AVR) in patients with severe aortic stenosis. Sokolow-Lyon voltage (SV1 + RV5/6) is possibly the most widely used criterion for ECG-LVH. The aim of this study was to determine whether decrease in Sokolow-Lyon voltage reflects left ventricular reverse remodeling detected by echocardiography after AVR. Of 129 consecutive patients who underwent AVR for severe aortic stenosis, 38 patients with preoperative ECG-LVH, defined by SV1 + RV5/6 of ≥3.5 mV, were enrolled in this study. Electrocardiography and echocardiography were performed preoperatively and 1 year postoperatively. The patients were divided into ECG-LVH regression group (n = 19) and non-regression group (n = 19) according to the median value of the absolute regression in SV1 + RV5/6. Multivariate logistic regression analysis was performed to assess determinants of ECG-LVH regression among echocardiographic indices. ECG-LVH regression group showed significantly greater decrease in left ventricular mass index and left ventricular dimensions than Non-regression group. ECG-LVH regression was independently determined by decrease in the left ventricular mass index [odds ratio (OR) 1.28, 95 % confidence interval (CI) 1.03-1.69, p = 0.048], left ventricular end-diastolic dimension (OR 1.18, 95 % CI 1.03-1.41, p = 0.014), and left ventricular end-systolic dimension (OR 1.24, 95 % CI 1.06-1.52, p = 0.0047). ECG-LVH regression could be a marker of the effect of AVR on both reducing the left ventricular mass index and left ventricular dimensions. The effect of AVR on reverse remodeling can be estimated, at least in part, by regression of ECG-LVH.

Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p 0.05). Of the three subsets, the proportion of non-Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p 0.01), whereas those of rTregs and aTregs were not different between the two groups. Moreover, the expression levels of cytotoxic T lymphocyte antigen 4, a functional cell surface molecule, in aTregs (p 0.05) and non-Tregs (p 0.05) were significantly higher in PAH patients compared with controls. These results suggested the non-Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH.

Background The epidemiological data of pulmonary hypertension (PH) due to left heart disease (LHD) are limited. This study investigated hemodynamic and clinical factors associated with mortality in patients with PH due to LHD. Methods and results We conducted a retrospective review in 243 patients with PH due to LHD, defined as mean pulmonary arterial pressure ≥25 mmHg and pulmonary wedge pressure >15 mmHg at rest in right heart catheterization. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Seventy-five patients died during an average follow-up of 52 months (range, 20-73 months). On multivariate analysis, only diastolic pulmonary vascular pressure gradient (DPG) ≥7 mmHg among hemodynamic measurements was a predictor of mortality. Elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), more severe New York Heart Association (NYHA) class, anemia, and renal dysfunction were more strongly associated with mortality. Mean right atrial pressure (RAP) and currently available markers of pulmonary vascular remodeling including transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) had no effect on survival. Conclusions DPG is weakly associated with mortality in PH due to LHD. Clinical factors such as NT-pro BNP, NYHA class, anemia and renal dysfunction are superior predictors. The prognostic ability of hemodynamic factors such as mean RAP, TPG, PVR and DPG is limited.

Background— Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. Methods and Results— This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P =0.01), the intra-arrest PCI was higher (88% versus 70%; P =0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25–51] versus 54 minutes [34–74 minutes]; P =0.002). Conclusions— Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.

Pathologically, the lesions responsible for acute coronary syndrome (ACS) are ruptures of vulnerable plaques (and occasionally fibrous-cap erosions or calcified nodules) with a superimposed thrombosis. We aimed to clarify the clinical presentations related to the morphologies of coronary lesions of ACS using intravascular ultrasound (IVUS) and optical coherence tomography (OCT).Seventy-five culprit lesions of ACS patients were clearly assessed with IVUS and OCT. Patients were classified into two groups based on the presence or absence of a rupture of a culprit plaque as identified by OCT. Clinical characteristics and lesion morphologies were compared between the two groups. Waist circumference was significantly greater (p0.02) and prevalence of the metabolic syndrome (MS) higher (p=0.0011) in the rupture group. The prevalence of prodromal angina was higher in patients without plaque ruptures (p0.0001). Using multivariate analysis, the MS and prodromal angina were independent predictors of rupture of a culprit coronary plaque (odds ratio (OR): 27.30, p0.003 and OR: 0.04, p=0.0004, respectively). Among the components of the MS, the prevalence of abdominal obesity was a significant independent predictor of rupture of a culprit plaque (OR: 4.24, p0.02).There are two presentations related to the coronary lesion morphologies of ACS: we should understand these aspects of ACS.

Background: Acute coronary syndrome (ACS) commonly results from vulnerable plaque rupture, and occasionally results from thrombus formation in lesions without plaque rupture. The aim of the present study was to clarify the clinical features of different etiology of ACS and clinical predictors of culprit plaque rupture assessed on intravascular ultrasound (IVUS). Methods and Results: One hundred and ten ACS patients with emergent coronary angiography were classified into 2 groups based on the presence or absence of culprit plaque rupture assessed on IVUS. Clinical characteristics were compared between the 2 groups. Culprit coronary plaque rupture was observed in 60 patients (55%). Patients with plaque rupture were younger and were more likely to be male (P

Summary Background Although the metabolic syndrome is associated with incident cardiovascular disease, low-density lipoprotein (LDL) cholesterol is a well-known risk factor for coronary atherosclerosis. The aim of this study was to clarify the clinical markers for coronary plaque vulnerability in acute coronary syndrome (ACS) patients (men) without the metabolic syndrome. Methods Consecutive Japanese men with ACS (n = 264) underwent emergent coronary angiography and B-mode carotid ultrasonography. Common carotid intima-media thickening and vascular dilatation were considered to indicate carotid artery remodeling. Patients were divided into two groups based on the number of complex plaques identified by coronary angiography. Results Abdominal obesity and low high-density lipoprotein cholesterol levels were frequently observed in overall patients with multiple complex coronary lesions. Although the metabolic syndrome was a significant independent predictor of multiple complex coronary lesions in overall ACS patients, a high LDL cholesterol level was an independent predictor in ACS patients without the metabolic syndrome. Carotid artery remodeling was an independent predictor of multiple complex coronary lesions in both overall patients and patients without the metabolic syndrome. Conclusion In ACS patients without the metabolic syndrome, high LDL cholesterol levels and carotid artery remodeling are important indicators for assessing the efficacy of aggressive treatments for secondary prevention of ACS.

The notions and methods discussed below will at least allow the screening of new types of drugs. New types of drugs in the screening stage will not only improve the synaptic mechanism for excitation and inhibition, as conventional drugs do, but will also improve the performance of the operating system of the brain. This suggests the existence of chemical compounds that cannot be inferred through limited (localized), sharp and realistic experimental analysis of biochemistry and neurophysiology, since the variables for the integration of varid phenomena in the brain must also be analyzed.

The testing of psychotropic drugs on humans requires that consciousness itself be evaluated. With laboratory animals, conscious activity cannot be diagnosed. How can this handicap be overcome?

A 10-h intraventricular infusion of 10 pmol of uridine from 19.00 to 05.00 h resulted in significant increases in sleep in otherwise saline-infused male rats (n = 8) during the environmental dark period (20.00-08.00 h). Increments of slow wave sleep (SWS) and paradoxical sleep (PS) were 21.0% and 68.1%, respectively, of the baseline value. This was due to increases in the frequencies of both SWS and PS episodes but not to their durations. Similar increases occurred the first recovery night under saline infusion, but sleep amounts returned to the baseline levels the second night. Brain temperature was not affected by uridine administration. A small dose of uridine (1 pmol/10 h) exerted no effect (n = 6) while larger doses (100 and 1000 pmol/10 h, each n = 5) resulted in slight but insignificant increases in SWS and PS. The 1000-pmol uridine administration seemed to be non-physiological since it brought about irregularities in locomotor activity and sleep-waking rhythms. Thus, authentic uridine exhibited the same sleep-enhancing effects as a naturally occurring active component of sleep-promoting substance, which was recently identified with uridine.

In order to purify sleep-promoting substances (SPS), brainstem extract obtained from sleep-deprived rats was fractionated over SP Sephadex and then Sephadex G10 to give two active fractions A and B. The active fraction A was further purified over G10 and then by means of high-performance liquid chromatography to afford two active fractions A-1 and A-2. A 10hr intraventricular infusion of SPS, both fractions A and B, exerted a profound SWS promoting effect on recipient rats. In comparison with baseline nights, nocturnal locomotor activity decreased by 40–60 % while total time of nocturnal SWS increased by 40–100 %. Daily amount of PS in control rats (ca 80 min) was increased by 40 % after intraperitoneal injection of SPS, but the sleep promoting effect of SPS disappeared after pronase treatment of it.

The process of analysis invloved in DBSAM was described based on both the processing flow and the acquired model data. In the first step, the behavior of a mouse was classified into moving stage (MV), deep sleep stage (EP) and OT stage, in which the brain activity of the mouse was near the consciousness level. In the second step, the vague OT stages were classified into stages of quietness during the wakefulness state (QU) and light sleep stages (LSP) by the logical matrix. Finally, the symbol presentation for the stage-linkage of multiple stages per 1 sec was demonstrated.