Role of oxygen holes in Li(x)CoO(2) revealed by soft X-ray spectroscopy.

The fundamental electronic structure of the widely used battery material Li(x)CoO(2) still remains a mystery. Soft x-ray absorption spectroscopy of Li(x)CoO(2) reveals that holes with strong O 2p character play an essential role in the electronic conductivity of the Co(3+)/Co(4+) mixed valence CoO(2) layer. The oxygen holes are bound to the Co(4+) sites and the Li-ion vacancy, suggesting that the Li-ion flow can be stabilized by oxygen hole back flow. Such an oxygen hole state of Li(x)CoO(2) is unique among the various oxide-based battery materials and is one of the key ingredients to improving their electronic and Li-ion conductivities.

Band structure of the heavily-electron-doped FeAs-based Ba(Fe,Co)2As2 superconductor suppresses antiferromagnetic correlations.

In the heavily-electron-doped regime of the Ba(Fe,Co)2As2 superconductor, three hole bands at the zone center are observed and two of them reach the Fermi level. The larger hole pocket at the zone center is apparently nested with the smaller electron pocket around the zone corner. However, the (pi,0) Fermi surface reconstruction reported for the hole-doped case is absent in the heavily-electron-doped case. This observation shows that the apparent Fermi surface nesting alone is not enough to enhance the antiferromagnetic correlation as well as the superconducting transition temperature.

Excitonic insulator state in Ta2NiSe5 probed by photoemission spectroscopy.

We report on a photoemission study of Ta2NiSe5 that has a quasi-one-dimensional structure and an insulating ground state. Ni 2p core-level spectra show that the Ni 3d subshell is partially occupied and the Ni 3d states are heavily hybridized with the Se 4p states. In angle-resolved photoemission spectra, the valence-band top is found to be extremely flat, indicating that the ground state can be viewed as an excitonic insulator state between the Ni 3d-Se 4p hole and the Ta 5d electron. We argue that the high atomic polarizability of Se plays an important role to stabilize the excitonic state.

Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function.

BACKGROUND: Recently, it has been reported that frequent premature ventricular contractions (PVCs) may be associated with causing heart failure in patients with left ventricular (LV) dysfunction. However, the prognostic significance of frequent PVCs in asymptomatic patients with a normal LV function is unclear. METHODS: Two hundred and thirty-nine consecutive patients presenting with frequent PVCs (>1000 beats/day) originating from the right or left ventricular outflow tract without any detectable heart disease were enrolled in the study. Structural heart disease was ruled out by echocardiography and cardiac magnetic resonance imaging, and Holter-ECG monitoring was repeated two or three times to evaluate the PVC prevalence at the initial evaluation. All patients were followed up for at least 4 years, and further observation was continued if possible. RESULTS: During an observation period of 5.6 (1.7) years, no patients exhibited any serious cardiac events. Although there was no significant change in the mean LV ejection fraction (LVEF) and mean LV diastolic dimension (LVDd), there was a significant negative correlation between the PVC prevalence and DeltaLVEF (p<0.001) and positive correlation between the PVC prevalence and DeltaLVDd (p<0.001). When the development of LV dysfunction was defined as DeltaLVEF>-6%, 13 patients exhibited LV dysfunction. For the prediction of the development of LV dysfunction, PVC prevalence and LVEF at the initial evaluation were independent predicting factors (p<0.01). CONCLUSION: Although the prognosis in patients with frequent PVCs was considered relatively benign, attention should be paid to the progression of the LV dysfunction during a long-term observation, especially in patients with a high PVC prevalence.

Fatal familial insomnia with an unusual prion protein deposition pattern: an autopsy report with an experimental transmission study.

We recently performed a post-mortem examination on a Japanese patient who had a prion protein gene mutation responsible for fatal familial insomnia (FFI). The patient initially developed cerebellar ataxia, but finally demonstrated insomnia, hyperkinetic delirium, autonomic signs and myoclonus in the late stage of the illness. Histological examination revealed marked neuronal loss in the thalamus and inferior olivary nucleus; however, prion protein (PrP) deposition was not proved in these lesions by immunohistochemistry. Instead, PrP deposition and spongiform change were both conspicuous within the cerebral cortex, whereas particular PrP deposition was also observed within the cerebellar cortex. The abnormal protease-resistant PrP (PrP(res)) molecules in the cerebral cortex of this case revealed PrP(res) type 2 pattern and were compatible with those of FFI cases, but the transmission study demonstrated that a pathogen in this case was different from that in a case with classical FFI. By inoculation with homogenate made from the cerebral cortex, the disease was transmitted to mice, and neuropathological features that were distinguishable from those previously reported were noted. These findings indicate the possibility that a discrete pathogen was involved in the disease in this case. We suggest that not only the genotype of the PrP gene and some other as yet unknown genetic factors, but also the variation in pathogen strains might be responsible for the varying clinical and pathological features of this disease.

Development of a flow estimation and control system of an implantable centrifugal blood pump for circulatory assist.

A bypass flow rate estimation and control system (BECS) for an implantable centrifugal blood pump (ICBP) has been developed in our institute. The estimated flow rate (EF) of the ICBP was derived from the electric power consumption, the rotating speed of a motor, and the blood viscosity presumed by the hematocrit and body temperature. The error in the EF was 0.5 +/- 0.4 L/min in in vivo experiments for 40 days. The rotating speed of the motor was controlled automatically every 200 ms to bring the EF in accord with the desired flow rate (DF). The reactivity and accuracy of the BECS were investigated in in vitro and in vivo experiments. The ICBP was operated by the BECS in a mock circuit in parallel with a pulsatile ventricular assist device (PVAD) to simulate left heart bypass. The reactivity was evaluated by changing the DF from 7 L/min to 5 L/min at an afterload of 160/97 mm Hg. To evaluate the accuracy of the BECS, the ICBP was driven under the aortic pressure of 110/85 mm Hg in the abdominal wall of an adult goat (70 kg). The DF was set at 5 L/min for 4 min for the goat in an awake condition. It took 13 s to change the flow rate in the in vitro experiment. The measured flow rate (MF) was maintained at 5.0 +/- 0.2 L/min by the BECS in vivo. In conclusion, the BECS has moderate reactivity and accuracy.

Intrathoracic and intraabdominal wall implantation of a centrifugal blood pump for circulatory assist.

An implantable centrifugal pump (ICP) 320 ml in volume and 830 g in weight has been developed for prolonged circulatory assist. The antithrombogenicity of the ICP is provided by a balancing hole in the center of the impeller. The watertightness and histocompatibility of the ICP are supported by its silicone ring seal and its casing of titanium and acrylic resin, respectively. The total efficiency of the ICP was 30% at a 5 L/min flow rate and a 100 mm Hg head. The heat generation, watertightness, and anatomical fitting of the ICP were assessed in an intrathoracic implantation in a goat (66 kg) and in an intraabdominal wall implantation in a goat (70 kg). Warfarin was given for anticoagulation in each experiment to keep the prothrombin time around 1.7 times that of the control. The temperatures of the pump surface, the pleura, and the room were measured every 3 h. Anatomical fitting was evaluated by pathological observation after the termination of the experiment. The ICP could run for 40 days in the chest cavity and for 11 days in the abdominal wall. The temperature of the motor remained about 1.8 degrees C higher than the reference in both experiments. The ICP was completely covered by a layer of smooth fibrous tissue. The moisture content of the seals remained normal. Although a small amount of atelectasis was found in the lingula, neither lung adhesion nor necrotic change of the chest wall was observed. The inflammation of the surrounding tissue including foreign body reaction and thermal burn was minimal. In conclusion, the ICP has satisfied in vivo testing of its watertightness, exothermicity, and anatomical fitting.

Development of design methods of a centrifugal blood pump with in vitro tests, flow visualization, and computational fluid dynamics: results in hemolysis tests.

There are few established engineering guidelines aimed at reducing hemolysis for the design of centrifugal blood pumps. In this study, a fluid dynamic approach was applied to investigate hemolysis in centrifugal pumps. Three different strategies were integrated to examine the relationship between hemolysis and flow patterns. Hemolytic performances were evaluated in in vitro tests and compared with the flow patterns analyzed by flow visualization and computational fluid dynamic (CFD). Then our group tried to establish engineering guidelines to reduce hemolysis in the development of centrifugal blood pumps. The commercially available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the dimensions of 2 types of gaps between the impeller and the casing, the axial and the radial gap, were varied. Four impellers with different vane outlet angles were also prepared and tested. Representative results of the hemolysis tests were as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100 L, respectively. The backward type vane and the standard one resulted in NIH values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that small gaps led to more hemolysis and that the backward type vane caused more hemolysis. Therefore, the design parameters of centrifugal blood pumps could affect their hemolytic performances. In flow visualization tests, vortices around the impeller outer tip and tongue region were observed, and their patterns varied with the dimensions of the gaps. CFD analysis also predicted high shear stress consistent with the results of the hemolysis tests. Further investigation of the regional flow patterns is needed to discuss the cause of the hemolysis in centrifugal blood pumps.

Prolonged nonpulsatile left heart bypass with reduced systemic pulse pressure causes morphological changes in the aortic wall.

We investigated the morphological changes in the aorta due to reduced systemic pulse pressure in prolonged nonpulsatile left heart bypass (LHB). Nineteen adult goats were divided into 3 groups, the nonpulsatile group in which nonpulsatile LHB was conducted, the pulsatile group in which pulsatile LHB was conducted, and the control group used as the normal control. The average aortic pulse pressures were 12, 47, and 37 mm Hg, respectively. The descending aorta was subjected to morphological examination. In the nonpulsatile group, the wall was significantly thinner, and the volume ratio of smooth muscle cells (SMCs) was much lower. In terms of the SMC type classification, the proportion of SMCs with low activity and low contractility was higher, and the cell density of the SMCs was increased compared to those in the other groups. These results indicate that prolonged nonpulsatile LHB causes morphological atrophic changes in the aorta.

Hemodynamic and humoral conditions in stepwise reduction of pulmonary blood flow during venoarterial bypass in awake goats.

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 +/- 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50, 25, 10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 +/- 14 to 66 +/- 3 mmHg and from 1,288 +/- 77 to 740 +/- 73 dyne.sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 concentration increased from 1.5 +/- 0.6 to 8.8 +/- 0.6 pg/ml following the decrease in PAF from 100 to 0%. The renin-angiotensin system increased in proportion to the decrease in PAF. In contrast, the epinephrine and norepinephrine concentrations (60 +/- 10 and 227 +/- 80 pg/ml, respectively, at 100% PAF) did not change appreciably even at 10% PAF, but were markedly elevated to 335 +/- 117 and 2,088 +/- 1,503 pg/ml at 0% PAF. The antidiuretic hormone level similarly changed. In conclusion, decrease in PAF during VAB exerts significant effects on hemodynamics in a proportional manner and on vasoactive humoral factors in a diverse manner.

Development of an implantable centrifugal blood pump for circulatory assist.

An implantable centrifugal pump (ICP) for prolonged circulatory assist has been developed, at 320 ml and 830 g. A central balancing hole was made in its impeller for better antithrombogenicity. Waterproofing and histocompatibility were supported by a silicone seal and a casing made of titanium and acrylic resin. Overall efficiency was 30% and normalized index of homolysis was 0.003 mg/dl, the same value as the BP-80, at a flow rate of 5 L/min and a head of 100 mmHg. Antithrombogenicity and hemolytic properties of the ICP were investigated in paracorporeal implantation in three goats (61-71 kg). Exothermicity, anatomic fit, and water tightness of the ICP were evaluated in intrathoracic implantation in an adult goat (66 kg). The ICP could run paracorporeally for 50, 200, and 381 days. There was no thrombus in the ICP after 381 days' pumping, and the ICP could run in the chest cavity for 40 days. The temperature of the motor rose 1.8 +/- 0.3 degrees C from that of the pleura. Moisture content of the seal remained normal. The ICP was completely covered with smooth fibrous tissue. Although a small area of atelectasis was found in the lingula, neither lung adhesion nor necrosis of the chest wall was observed. The ICP has satisfactory antithrombogenicity, hemolytic property, water tightness, anatomic fit, and exothermicity for use as an implantable circulatory assist device.

In vitro and in vivo heat dissipation of an electrohydraulic totally implantable artificial heart.

The authors evaluated the heat transfer characteristics of an electrohydraulic totally implantable artificial heart (EH-TAH) developed at our institute. In three in vitro experiments, the heat dissipation of the EH-TAH was investigated. First, the EH-TAH was connected to a closed mock circuit filled with 1 L of saline, and driven at an input power of 20 W. The estimated heat conducted to the blood was approximately 10.3 W, which was almost half of the input power. Second, we simulated heat transfer with the circulation of a calf by using a heat exchanger. The amount of heat dissipating directly from the EH-TAH surface was calculated to be 10 W. Third, the temperature of the actuator examined with thermography was found to be almost uniform, and no prominent high temperature area was observed. In an in vivo study, the EH-TAH was implanted for 10 days in a calf weighing 62 kg. The input power was 18 +/- 2 W, the temperature of the actuator-tissue contacting surface was 39.4 +/- 0.8 degrees C, and that of the pump blood chamber was 39.8 +/- 0.4 degrees C. This slight temperature elevation was thought to be attributable to heat dissipation to the blood. On histologic study of the chest wall and the lung in contact with the actuator, vascularized connective tissue envelopes were observed, but unfavorable side effects, such as tissue necrosis, were not observed. These results suggest that the thermal effect of this system is acceptable at the input power used.

Early changes in circulating blood volume and volume regulating humoral factors after implantation of an electrohydraulic total artificial heart.

The early changes in circulating blood volume (CBV) and volume regulating humoral factors after implantation of an electrohydraulic total artificial heart (EH-TAH) were investigated in a calf and compared with results in a sham operated control calf. CBV was measured by the dye dilution method using indocyanine green. CBV and humoral factors were periodically investigated. In the EH-TAH implanted calf, the cardiac output was estimated at 6-7 L/ min (94-109 ml/kg/min), and the aortic pressure and aerobic metabolic condition were favorable. Nevertheless, the CBV was increased to 132 and 168% of the pre-operative value (range in the control calf, 83-103%) on post operative days 4 and 8, respectively. The atrial natriuretic peptide level on days 2, 5, and 7 was 23, 170, and 240 (in the control calf, 19-61) pg/ml, respectively, and the antidiuretic hormone level was 7.3, 2.0, and 1.3 (0.5-1.3) pg/ ml, respectively. The plasma renin activity was 3.2, 3.7, and 3.1 (0.5-0.3) ng/ml/hr, respectively. The angiotensin-I and angiotensin-II levels were also increased in the EH-TAH implanted calf. It is concluded that significant water retention occurs even at sufficient cardiac output early after EH-TAH implantation. The changes in humoral factors are suggested to arise secondary to the increased CBV or other unknown factors.

Establishment of flow estimation for an implantable centrifugal blood pump.

A less invasive and non thrombogenic flow estimation of an implantable centrifugal blood pump (ICBP) has been developed, which was derived from electric power consumption, the rotating speed of a motor, and blood viscosity presumed by hematocrit and body temperature. The power consumption and the rotating speed of the motor were measured by a wattmeter every 0.2 sec. Accuracy and stability of the estimated flow (EF) were investigated during in vitro and in vivo experiments. The EF was compared with a measured flow rate (MF) monitored by an electromagnetic flowmeter. During in vitro experiments, the EF and MF were measured at 79 operating points. The ICBP was driven in a closed mock loop filled with goat blood with hematocrit values of 21.5, 28, 34, and 42%. During in vivo experiments, the ICBP was implanted in the chest cavity of a goat and driven for 40 days with continuous estimation of the bypass flow rate. Blood was taken to determine hematocrit value several times a week. The temperature of the pleura away from the ICBP was measured every 15 min. A linear correlation between the EF and MF was observed, and the correlation coefficient between the EF and MF was 0.99 during in vitro examinations. An averaged error of the EF was 0.5 L/min, with the MF ranging from 2.3 to 8.1 L/min during in vivo experiments. In conclusion, flow estimation was established with good stability and accuracy in both in vitro and in vivo experiments.

Characteristics of mixed venous oxygen saturation and physical activity as parameters for artificial heart control.

Mixed venous oxygen saturation (SvO2) and physical activity (PhyAc) are practical candidates as parameters of total artificial heart (TAH) control because SvO2 can be measured through a transparent blood pump housing with infrared rays and PhyAc can be calculated from signals of an accelerometer used for rate response pacemakers. Although the methods for measurement of the parameters have already been developed, characteristics of these parameters for TAH control, such as during exercise, are still unclear and were examined in this study. SvO2, cardiac output (CO), and PhyAc were measured as parameters. Multi-stage treadmill exercise tests were performed. Difference values (DVs) from the value at the start of exercise showed better correlation than did absolute values. Correlation coefficients between DV in CO and DV in SvO2 and between DV in CO and PhyAc were high at -0.82 and 0.72, while the time constants for the change of SvO2 and CO to the PhyAc change were 26 and 32 sec. Although the correlation coefficient between the CO and SvO2 was higher than that between CO and PhyAc, PhyAc responded more quickly to the speed change compared with the response of SvO2 and CO. It was concluded that SvO2 and PhyAc were useful parameters with different characteristics for TAH control during exercise.

Morphologic changes of the aortic wall due to reduced systemic pulse pressure in prolonged non pulsatile left heart bypass.

The morphologic changes of the aortic wall due to reduced systemic pulse pressure in prolonged non pulsatile left heart bypass (LHB) were investigated. Sixteen adult goats were divided into three groups: the non pulsatile group in which non pulsatile LHB was conducted for 137 days on average, the pulsatile group in which pulsatile LHB was conducted for 79 days on average, and the control group used as the normal control. The average aortic pulse pressures were 12, 48, and 37 mmHg, respectively. At the end of the experiments, the descending aorta was excised and subjected to morphologic examination. The wall thickness of the aorta in the non pulsatile group (1.4 mm) was significantly thinner than that in the pulsatile group (2.2 mm) and the control group (2.0 mm), and the volume ratio of smooth muscle cells (SMC) in the non pulsatile group (37%) was lower than that in the pulsatile group (48%) and the control group (49%). In SMC classification, the proportion of SMC with low activity and low contractility in the non pulsatile group (57%) was high as compared with that in the pulsatile (2%) and control (5%) groups. These results strongly indicate that prolonged non pulsatile LHB causes substantial morphologic changes in the aorta.

Noninvasive pump flow estimation of a centrifugal blood pump.

A flow rate estimating method was investigated for a centrifugal blood pump developed in our institute. The estimated flow rate was determined by the power consumption, the rotating speed of the motor, and the hematocrit value. The power consumption and the rotating speed of the motor were measured with a wattmeter. The examinations were performed in a closed mock loop filled with goat blood with hematocrit values of 21.5%, 28%, 34%, and 42%. Measured values of blood viscosity were 2.47, 3.09, 3.71, and 5.07 mPa.s at a share rate of 37.5/s, respectively. A linear correlation between the power consumption and the pump flow rate was observed in all hematocrit values. But variations in hematocrit caused a difference in the flow rate up to 1.1 L/min at the same power consumption and rotating speed. Effects of blood viscosity on the flow estimation were corrected by the hematocrit value. The value of the coefficient of determination, R2, between the estimated flow rate and the measured flow rate was 0.988. These results may indicate that the flow estimating method calculated by the power consumption of the motor, the rotating speed, and the hematocrit value is useful in the clinical situation.

Long-term evaluation of a nonpulsatile mechanical circulatory support system.

Antithrombogenicity of a centrifugal pump (CP) developed in our institute is provided by a central balancing hole (BH) in the impeller. A current CP, the National Cardiovascular Center (NCVC)-2, was ameliorated to improve antithrombogenicity, whereby the BH diameter was widened to improve self washout flow velocity, and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of these modifications were assessed in a long-term in vivo experiment. The antithrombogenicity, hemolytic property, and mechanical durability of the NCVC-2 were investigated in 3 goats. The NCVC-2 was installed paracorporeally between the left atrium and the aorta and driven as long as possible at rotating speeds of about 2,800 rpm. The NCVC-2 ran for 50, 200, and 367+ days. The mean bypass flow rates were 6.8, 5.0, and 5.3 L/min, respectively. Creatinine, blood urea nitrogen (BUN), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) did not increase until one week before termination. Plasma free hemoglobin was kept to a level less than 15 mg/dl, except for the last week of the second case. These results indicate that the NCVC-2 has excellent antithrombogenicity, an acceptable hemolytic property and the necessary durability for prolonged use.

Application of hydrogen absorbing alloys to medical and rehabilitation equipment.

As power sources for rehabilitation equipment, electric, hydraulic, and pneumatic actuators have been used. However a more human-sized and higher powered actuator that can reduce the equipment size is desired. A new metal hydride (MH) actuator that uses the reversible reaction between the heat energy and mechanical energy of a hydrogen absorbing alloy has recently attracted much attention. The MH actuator is characterized by its small size, low weight, noiseless operation and a compliance similar to that of the human elbow joint. Therefore, the MH actuator has the characteristic of being light and easy to use and so is suitable for use in medical and rehabilitation applications. Some lifting devices using this actuator have already been developed and are being used for the care of the aged and disabled. The characteristics of the MH actuator are presented and then some applications are introduced in this paper. It is our opinion that in our aging society the MH actuator will play an important role in the development of medical and rehabilitation equipment.

Effects of self washout structure on the antithrombogenicity and the hemolytic properties of a centrifugal pump.

Antithrombogenicity in an initial type (N1) of a centrifugal pump (CP) developed in our institute is provided by the central balancing hole of an impeller. A new CP (N2) was modified to obtain better antithrombogenicity, in which the balancing hole was widened to improve self washout flow velocity (Vsf), and an edge of the thrust bearing was rounded off to minimize flow separation. Effects of the modifications were assessed in vitro and in vivo studies. The Vsf of the N1 and the N2 evaluated by a Doppler velocimeter were 12.8 and 22.1 cm/s, respectively. Flow around the thrust bearing, which was visualized by a light cutting method, confirmed less flow stagnation in the N2. The hemolytic indices of the N1 and the N2 were 0.023 and 0.008 mg/dl, respectively. In vivo antithrombogenicity and the hemolytic properties of the N2 and the N1 were investigated without anticoagulation therapy in 3 goats. In each goat the N2 was driven for 1 week and exchanged for the N1, which was driven for the same period. Red thrombi at the thrust bearing were found in 2 N1s, and 2 small thrombi were on the impeller of another N1, whereas a thrombus of less than 1 mm3 at the TB was noted in 1 N2. Plasma free hemoglobin was not increased in either CP. These results indicate that the N2 has better antithrombogenicity and hemolytic properties than the N1.