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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 649 records · Page 36Linked to original sources

Optical sensor for hemoglobin content and oxygen saturation. Application to artificial heart research.

A hybrid optical sensor that can measure both hemoglobin content ([ Hb]) and oxygen saturation (OS) of whole blood has been developed. The measurement errors in [Hb] and OS are 0.5 g% and 1.2%, respectively, over an hematocrit range of 25 to 45%. The oxygen content derived from the optical sensor yielded a standard error of 0.1 to 0.2 vol%. The sensors were mounted in the outflow ports of left and right artificial hearts that maintained the entire circulation and were used to chronically monitor arterial and mixed venous [Hb] and OS. In combination with pump output and pressure measurements, oxygen delivery and oxygen consumption of the animal was derived on-line using a microprocessor. In the experiment that lasted 40 days, both sensors functioned well, with stable measurements, and no thrombus formation around the sensor at the time of autopsy. The optical sensors are useful for monitoring cardiopulmonary function and metabolic status of patients without requiring blood samples. In addition, the pump output may be controlled through the level of mixed venous OS or in combination with the arterial OS.

Animals↗

A synthetic tetrapeptide as a novel platelet-preserving agent during cardiopulmonary bypass.

The possibility of using the synthetic tetrapeptide arginine-glycine-aspartic acid-serine (Arg-Gly-Asp-Ser, RGDS), which was recently identified as the common cell attachment site of adhesive plasma proteins, for platelet preservation during cardiopulmonary bypass (CPB) was investigated. The synthetic RGDS inhibited platelet aggregation and adhesion and secretion of thromboxane A2 in a dose-dependent manner, due to antagonistic inhibition via ligand-receptor interaction. Platelet consumption during CPB was drastically reduced by the administration of RGDS with no remarkable change in hemodynamics and a fairly rapid recovery of platelet functions. Electron microscopic observation revealed that this platelet-preserving effect of RGDS resulted from the inhibition of adhesion and aggregation on the artificial surface. These strongly indicate that the cell attachment site of adhesive plasma proteins plays an important role in platelet consumption during CPB. The synthetic RGDS acting as an antagonist of the platelet membrane receptor, is a novel platelet-preserving agent, especially useful when using an extracorporeal circuit with a large blood-material contact area, such as CPB.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Animals↗

In vitro and in vivo evaluation of a left-right balancing capacity of an interatrial shunt in an electrohydraulic total artificial heart system.

The authors evaluated the basic performance of an interatrial shunt (IAS) made by punching a hole in the atrial septum, in accommodating the left-right imbalance in our electrohydraulic total artificial heart (EHTAH) system. In an in vitro study conducted in a closed mock circuit connected with the EHTAH, the interatrial pressure gradient changed in compliance with the amount of bronchial flow and the size of the IAS. The IAS of 4.4 mm diameter or larger maintained the interatrial pressure gradient within physiologically permissible limits when the amount of bronchial flow was 5% of cardiac output or less. A left-to-right one-way valve made of a piece of pericardium, a possible option in this IAS method, successfully prevented right-to-left reverse shunt flow through the IAS. In a chronic in vivo study using a calf implanted with the EHTAH for 10 days, a 4.5 mm IAS without the one-way valve demonstrated satisfactory dynamic left-right balancing capacity with a stable interatrial pressure gradient of 4 +/- 1 mmHg over a wide range of atrial pressures. No thrombus was found in or around the IAS at autopsy. The authors conclude that the IAS is a simple and promising means of left-right balancing in the EHTAH system.

Animals↗

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.

Animals↗

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.

Angiotensin I↗

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.

Animals↗

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.

Animals↗

Inhibition by Porphyromonas gingivalis LPS of apoptosis induction in human peripheral blood polymorphonuclear leukocytes.

Many factors, such as cytokines and bacterial products, are known to affect the life-span of polymorphonuclear leukocytes (PMNs). We investigated here whether Porphyromonas gingivalis (P.gingivalis) LPS slows down the apoptotic process of PMNs. During incubation in regular culture medium, the viability of PMNs progressively declined, producing apoptotic cells, characterized by chromatin condensation, internucleosomal DNA fragmentation, cell shrinkage and blebbing of plasma membrane. P.gingivalis LPS significantly increased the viability of PMNs and reduced the production of fragmented DNA, as efficiently as E.coli LPS. The present study suggests that the retardation of PMNs apoptosis by P.gingivalis LPS may modulate the restoration of acute inflammation in the periodontal tissues, where activated PMNs accumulate.

Apoptosis↗

Radical intensity and cytotoxic activity of curcumin and gallic acid.

Natural phenolic compounds, curcumin and gallic acid, were compared for their cytotoxic activity in relation to their radical modulating activity. These two compounds induced apoptotic cell death in human promyelocytic leukemic HL-60 cells and human oral squamous carcinoma HSC-4 cells. Curcumin was more cytotoxic than gallic acid. Catalase reduced significantly the cytotoxic activity of gallic acid, but not that of curcumin. ESR spectroscopy demonstrated that curcumin produced radicals under alkaline conditions, scavenged the superoxide anion radical, and enhanced the radical intensity of sodium ascorbate at higher concentrations. As compared with curcumin, gallic acid produced higher amounts of radicals and more efficiently scavenged the superoxide anion radical. Gallic acid reduced the radical intensity of sodium ascorbate, suggesting a possible interaction between these two compounds. These data suggest that curcumin and gallic acid induce apoptosis by different mechanisms.

Antineoplastic Agents↗

Long-term results of corticosteroid administration via appendicostomy in patients with ulcerative colitis involving the entire colon.

BACKGROUND: Ulcerative colitis (UC) of an unknown etiology frequently demonstrates repeated active and inactive stages. As a result, it is difficult to sustain long-term remission under conservative therapy. METHODS: Ten patients who presented suffering from UC involving the entire colon were treated. All patients had been previously treated at other hospitals usually with sulphasalazine and either corticosteroids or steroid enemas for the primary complaints of muco-bloody stool or frequent diarrhea. All patients underwent either an appendicostomy or cecostomy, and were injected with dexamethasone via an artificial fistula twice a day. RESULTS: This treatment led to remission, and, as a result, the symptoms of anal bleeding or muco-bloody stools disappeared in all patients. Radiological, endoscopic, and pathological studies revealed a dramatic response to steroid injection from the fistula. The mean follow-up period was 44.7 months (3-122 months). Eight patients remained free from any symptoms of UC. One underwent a proctocolectomy because of side effects due to steroid treatment. The other patient died suddenly of unknown causes. The mean symptom-free period after cecal injection was 39.5 months (1-119 months). The mean proportion of disease free period from UC, compared with the total follow-up period after surgery, was 88%. After remission, eight patients were able to return to a normal lifestyle at home using a peritoneal button. They could also take a bath and continue their school or social lives in almost the same way as healthy persons. CONCLUSIONS: We thus recommend this new, minimally-invasive therapy for patients with UC involving the entire colon who demonstrate resistance to conventional conservative therapy. As a result of such treatment, all patients were able to achieve a comfortable lifestyle after undergoing minimally-invasive surgery.

Adult↗

Amino acid utilization during cell growth and apoptosis induction.

The amino acid utilization between human promyelocytic leukemia (HL-60), human oral squamous carcinoma (HSC-2, HSC-4, NA), human salivary gland tumor (HSG) and rat neuron cells (PC-12) were compared, using amino acid analyzer. All these cells consumed four essential amino acids (valine, methionine, isoleucine, leucine), glutamine and arginine, whereas they produced glycine, alanine and ammonia, without significantly affecting threonine, tyrosine, phenylalanine, histidine or lysine concentration. Serine and glutamine utilization varied considerably from cell to cell. HL-60 cells consumed serine and arginine at much higher rates than other cells. Serine depletion accumulated the G1 arrested cells, and produced increasing numbers of the apoptotic cells. Supplementation of serine significantly extended the period of logarithmic cell growth. During apoptosis induction of HL-60 cells by dopamine, sodium ascorbate or sodium 5,6-benzylidene-L-ascorbate, the oxidation of methionine to methionine sulfoxide was enhanced, but the consumption of serine, glutamine and arginine was reduced. In the presence of HL-60 cells, the methionine oxidation was significantly inhibited, suggesting the antioxidant action of the cells. These present study suggests the importance of re-evaluation of culture condition for each cell lines.

Amino Acids↗