Relation between ventriculoarterial coupling and myocardial energetics in patients with idiopathic dilated cardiomyopathy

AbstractObjectives. The purpose of this study was to evaluate left ventricular contractility, arterial loading conditions and the way their interaction affects myocardial energetics.Background. Ventriculoarterial coupling, defined as the ratio of effective arterial elastance to left ventricular end-systolic elastance, is known to reflect the mechanoenergetic performance of the heart. However, relations between the coupling and efficiencies of energy transfer from oxygen consumption to hydraulic energy have not been fully investigated in failing hearts.Methods. Pressure-volume data were measured in 23 patients with idiopathic dilated cardiomyopathy by using a conductance catheter, and myocardial oxygen consumption was obtained simultaneously in 16 patients by a double-thermistor coronary sinus catheter. End-systolic elastance was determined by transient inferior cava occlusion.Results. Data are reported as mean value ± SE. Ventriculoarterial coupling at baseline was 3.14 ± 0.28. It decreased from 3.12 ± 0.43 to 1.86 ± 0.15 (p < 0.05) for the group receiving dobutamine infusion and from 3.16 ± 0.45 to 1.78 ± 0.22 (p < 0.01) for the group receiving the oral phosphodiesterase inhibitor MS-857. The ratio of pressure-volume area to myocardial oxygen consumption had a positive correlation with ventriculoarterial coupling. The ratio of external work to pressure-volume area had a hyperbolic correlation with the coupling. The mechanical efficiency defined as the ratio of external work to myocardial oxygen consumption remained within a narrow range (16.4 ± 1.2%).Conclusions. The degree of ventriculoarterial coupling is far from optimal and the cardiovascular performance is severely depressed mechanically and energetically in patients with idiopathic dilated cardiomyopathy. Although inotropic agents improve the coupling, they have a minimal effect on mechanical efficiency

Early hemoperfusion with an immobilized polymyxin B fiber column eliminates humoral mediators and improves pulmonary oxygenation

INTRODUCTION: The objective of this study was to clarify the efficacy and mechanism of action of direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) in patients with acute lung injury or acute respiratory distress syndrome caused by sepsis. METHOD: Thirty-six patients with sepsis were included. In each patient a thermodilution catheter was inserted, and the oxygen delivery index and oxygen consumption index were measured. DHP-PMX was performed in patients with a normal oxygen delivery index and oxygen consumption index (> 500 ml/minute per m(2 )and >120 ml/minute per m(2), respectively). The Acute Physiology and Chronic Health Evaluation II score was used as an index of the severity of sepsis, and survival was assessed after 1 month. The humoral mediators measured were the chemokine IL-8, plasminogen activator inhibitor-1, and neutrophil elastase (NE). These mediators were measured before DHP-PMX treatment, and at 24, 48, and 78 hours after the start of treatment. The arterial oxygen tension (PaO(2))/fractional inspired oxygen (FiO(2)) ratio was measured before DHP-PMX treatment and at 24, 48, 72, 92, and 120 hours after the start of treatment. RESULTS: All patients remained alive after 1 month. Before DHP-PMX treatment, the Acute Physiology and Chronic Health Evaluation II score was 24 ± 2.0, the IL-8 level was 54 ± 15.8 pg/ml, plasminogen activator inhibitor-1 was 133 ± 28.1 ng/ml, and NE was 418 ± 72.1 μg/l. These three humoral mediators began to decrease from 24 hours after DHP-PMX treatment, and the decline became significant from 48 hours onward. The PaO(2)/FiO(2 )ratio was 244 ± 26.3 before DHP-PMX treatment but improved significantly from 96 hours onward. There were significant negative correlations between the PaO(2)/FiO(2 )ratio and blood levels of NE and IL-8. CONCLUSION: The mechanism of action of DHP-PMX is still not fully understood, but we report the following findings. The mean blood levels of plasminogen activator inhibitor-1, NE, and IL-8 were significantly decreased from 48 hours after DHP-PMX treatment. The mean PaO(2)/FiO(2 )ratio was significantly improved from 96 hours after DHP-PMX treatment. Improvement in the PaO(2)/FiO(2 )ratio appeared to be related to the decreases in blood NE and IL-8 levels

Integral Effects of Systemic Nitric Oxide Synthase Inhibition on Carotid Arterial Compliance

Decreased arterial compliance (increased arterial stiffness) is associated with cardiovascular events. Nitric oxide regulates vascular tone, which can influence arterial compliance. We previously investigated the effects of systemic nitric oxide synthase (NOS) inhibition on arterial compliance under the systemic α-adrenergic receptor blocking. In the present study, we investigated the effect of systemic NOS inhibition alone on central arterial compliance (via carotid arterial ultrasound imaging and applanation tonometry). Eighteen apparently healthy young adults (26±1 years) underwent intravenous infusions of NG-monomethyl-L-arginine (L-NMMA) or placebo (saline) on separate days. In the placebo control condition, no significant changes were observed in mean arterial pressure, cross-sectional compliance, and β-stiffness index. Mean arterial pressure increased significantly (84±2 vs. 96±3 mmHg) after the administration of L-NMMA, whereas there were no significant changes in cross-sectional compliance (0.11±0.01 vs. 0.12±0.01 mm2/mmHg), β-stiffness index (6.44±0.37 vs. 5.51±0.41 unit), or isobaric arterial compliance. Theses results in young healthy adults are not consistent with the idea that carotid arterial compliance is modulated by nitric oxide. Grant Support: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (18300215, 18650186), JSPS Postdoctoral Fellowships for Research Abroad, and NIH grant AG20966

Hard to "tune in": neural mechanisms of live face-to-face interaction with high-functioning autistic spectrum disorder

Persons with autism spectrum disorders (ASD) are known to have difficulty in eye contact (EC). This may make it difficult for their partners during face to face communication with them. To elucidate the neural substrates of live inter-subject interaction of ASD patients and normal subjects, we conducted hyper-scanning functional MRI with 21 subjects with autistic spectrum disorder (ASD) paired with typically-developed (normal) subjects, and with 19 pairs of normal subjects as a control. Baseline EC was maintained while subjects performed real-time joint-attention task. The task-related effects were modeled out, and inter-individual correlation analysis was performed on the residual time-course data. ASD-Normal pairs were less accurate at detecting gaze direction than Normal-Normal pairs. Performance was impaired both in ASD subjects and in their normal partners. The left occipital pole (OP) activation by gaze processing was reduced in ASD subjects, suggesting that deterioration of eye-cue detection in ASD is related to impairment of early visual processing of gaze. On the other hand, their normal partners showed greater activity in the bilateral occipital cortex and the right prefrontal area, indicating a compensatory workload. Inter-brain coherence in the right IFG that was observed in the Normal-Normal pairs (Saito et al., 2010) during EC diminished in ASD-Normal pairs. Intra-brain functional connectivity between the right IFG and right superior temporal sulcus (STS) in normal subjects paired with ASD subjects was reduced compared with in Normal-Normal pairs. This functional connectivity was positively correlated with performance of the normal partners on the eye-cue detection. Considering the integrative role of the right STS in gaze processing, inter-subject synchronization during EC may be a prerequisite for eye cue detection by the normal partner

Altered awareness of action in Parkinson’s disease: evaluations by explicit and implicit measures

Deficits in the integration of motor prediction and its feedback have been reported in Parkinson's disease. Conscious awareness of action is proposed to emerge under the integration of motor prediction and its feedback. Thus, it may lead to changes in the awareness of the authorship of action (in other words, the sense of agency) in Parkinson's disease. We have employed both explicit and implicit measures to assess the awareness of action in Parkinson's disease and matched controls. As an explicit measure, an action recognition task requiring explicit judgments was used. Patients showed less attribution of their movements to non-biased and angular-biased visual feedbacks. As an implicit measure, the temporal attraction between the perceived time of actions and their effects, which is known as intentional binding task, was used. While action-effect association was observed in the control group, actions were not experienced as having shifted towards their subsequent effects in the patient group. These tendencies were consistent regardless of the side of the asymmetrical motor symptoms. These results may reflect an underlying abnormality in the awareness of voluntary action in Parkinson's disease

ラット肝腫瘍モデルにおける化学療法の早期効果判定に有用なダイナミック造影超音波のパラメータについて

Objectives: The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model. Material and Methods: Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan, n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters. Pearson’s correlation coefficients (r) between tumor size and parameters in the control group were calculated. In the treatment group, relative changes of parameters in the first 3 days were compared between responder and non-responder (<20% and ≥20% increase in size on day 10, respectively). Results: PI, k value, PI × k, and TTP significantly correlated with tumor growth (r = 0.513, 0.911, 0.665, and 0.741, respectively). The mean RC in k value among responders (n = 6) was significantly lower than non-responders (n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003). Conclusion: Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.博士（医学）・甲第879号・令和5年3月15

Autistic empathy toward autistic others.

自閉スペクトラム症がある方々による、自閉スペクトラム症がある方々に対する共感. 京都大学プレスリリーズ. 2014-11-06.Individuals with Autism Spectrum Disorder (ASD) are thought to lack self-awareness and to experience difficulty empathising with others. Although these deficits have been demonstrated in previous studies, most of the target stimuli were constructed for typically developing (TD) individuals. We employed judgment tasks capable of indexing self-relevant processing in individuals with and without ASD. Fourteen Japanese males and one Japanese female with high-functioning ASD (17-41 years of age) and 13 Japanese males and two TD Japanese females ( 22-40 years of age), all of whom were matched for age and full and verbal intelligence quotient scores with the ASD participants, were enrolled in this study. The results demonstrated that the ventromedial prefrontal cortex was significantly activated in individuals with ASD in response to autistic characters and in TD individuals in response to non-autistic characters. Whereas the frontal-posterior network between the ventromedial prefrontal cortex and superior temporal gyrus participated in the processing of non-autistic characters in TD individuals, an alternative network was involved when individuals with ASD processed autistic characters. This suggests an atypical form of empathy in individuals with ASD toward others with ASD

Dual-time-point 18F-FDG PET imaging for diagnosis of disease type and disease activity in patients with idiopathic interstitial pneumonia

Purpose Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumors, to the differential diagnosis and prediction of disease progression in IIP patients. Methods Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n=21), nonspecific interstitial pneumonia (NSIP, n=18), and cryptogenic organizing pneumonia (COP, n=11), underwent 18F-FDG PET examinations at two time points: Scan 1 at 60 min (early imaging) and Scan 2 at 180 min (delayed imaging) after 18F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression, and disease types. To evaluate short term disease progression, all patients were examined pulmonary function test every 3 months for 1 year after 18F-FDG PET scanning. Results The early SUV for COP (2.47±0.74) was significantly higher than that for IPF (0.99±0.29, P=0.0002) or NSIP (1.22±0.44, P=0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity, and accuracy were 90.9%, 94.3%, and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1-year of follow-up (progressive group, 13.0±8.9%) than in cases without deterioration during the 1-year observation period (stable group, -16.8±5.9%, P<0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity, and accuracy were 95.5%, 100%, and 97.8%, respectively. Conclusion Early-SUV and RI-SUV obtained from dual-time point 18F-FDG PET are useful parameter for the differential diagnosis and prediction of disease progression in patients with IIP

ACTN1 Mutations Cause Congenital Macrothrombocytopenia

Congenital macrothrombocytopenia (CMTP) is a heterogeneous group of rare platelet disorders characterized by a congenital reduction of platelet counts and abnormally large platelets, for which CMTP-causing mutations are only found in approximately half the cases. We herein performed whole-exome sequencing and targeted Sanger sequencing to identify mutations that cause CMTP, in which a dominant mode of transmission had been suspected but for which no known responsible mutations have been documented. In 13 Japanese CMTP-affected pedigrees, we identified six (46%) affected by ACTN1 variants cosegregating with CMTP. In the entire cohort, ACNT1 variants accounted for 5.5% of the dominant forms of CMTP cases and represented the fourth most common cause in Japanese individuals. Individuals with ACTN1 variants presented with moderate macrothrombocytopenia with anisocytosis but were either asymptomatic or had only a modest bleeding tendency. ACTN1 encodes α-actinin-1, a member of the actin-crosslinking protein superfamily that participates in the organization of the cytoskeleton. In vitro transfection experiments in Chinese hamster ovary cells demonstrated that altered α-actinin-1 disrupted the normal actin-based cytoskeletal structure. Moreover, transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes, resulting in the production of abnormally large proplatelet tips, which were reduced in number. Our findings provide an insight into the pathogenesis of CMTP