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Biomedical subjects

Masahiro Nishida

Publications and source records attributed to Masahiro Nishida.

16 recordsLinked to original sources

The pivot wash in two impeller modes for the Baylor/Miwatec centrifugal blood pump.

A centrifugal blood pump with a double pivot impeller and an eccentric inlet port is being developed as an implantable artificial heart by the Baylor College of Medicine and Miwatec Co. Ltd. Flow visualization measurements were conducted to compare the flow around the pivot for two impeller operational modes: the top and the bottom contact modes. In the top contact mode, one-way flow in the pivot gap due to the eccentric vortex was observed, and sufficient wall shear rate to prevent thrombus formation was attained around the bottom pivot for over 1,400 rpm. Computational fluid dynamic analyses confirmed that the causes of the eccentric vortex were the inlet eccentricity and the pressure imbalance in the volute.

Assisted Circulation↗

Hemolysis resulting from surface roughness under shear flow conditions using a rotational shear stressor.

The degree of hemolysis as a function of surface roughness value and roughened area under shear flow conditions was investigated using a rotational shear stressor. The shearing portion of the stressor is cone shaped in its upper and lower positions, with a cylindrical central section. Surface roughness was applied to the cylindrical section. Bovine blood was sheared for 30 min over a set of roughened surfaces of between arithmetic mean roughness (Ra) 0.1 and 0.8 mm covering 10% of the surface area of the cylindrical section (equivalent to 1.8% of the whole blood contact area) at a shear rate of 3750/s. The threshold value thus obtained for rapid increase in hemolysis was between Ra 0.6 and 0.8 mm. When sheared with a roughened surface of Ra 0.8 mm applied to the cylindrical surface at areas between 0 and 100% (equivalent to between 0 and 18% of the whole blood-contacting area), the hemolysis level did not increase from 10 to 100%, but a significant difference was obtained between 0 and 10%. This suggests that red blood cells were destroyed not by fatigue failure caused by rolling on the roughened surface, but due to the high shear stress generated by surface roughness. Moreover, it appears that the shear stress was generated over the entire cylindrical section, regardless of the area of surface roughness.

Animals↗

Hemolysis caused by surface roughness under shear flow.

In this study, the relationship between the degree of roughness of blood contact surfaces under laminar shear flow conditions and the level of hemolysis resulting from this roughness was investigated using a rotational shear stressor. Unlike previous in vitro experiments that used a pumped circuit, the level of hemolysis was directly evaluated under a constant shear flow. In total, 1.8% of the blood contact area was roughened to an arithmetic mean roughness (Ra) value of between 0.4 and 9.2 microm by machine processing and a shear load was applied for 30 min at a shear flow rate of 3750 s(-1). As a result, the threshold Ra value for the induction of hemolysis was found to be between 0.4 and 0.8 microm. In addition, the results of this experiment suggested that the high shear stress resulting from surface roughness plays a major role in determining the level of hemolysis caused by surface roughness.

Animals↗

The hemolytic characteristics of monopivot magnetic suspension blood pumps with washout holes.

The hemolytic characteristics of monopivot magnetic suspension blood pumps as a function of impeller washout hole configuration and female pivot shape are observed. The pump impellers are designed with three washout hole configurations for blood circulation, and four female pivot shapes to reduce blood stagnation and to enhance antithrombogenicity. The hemolytic characteristics of the monopivot pumps were observed to be better than those of a currently available commercial centrifugal blood pump, BP-80, and changed to be nearly equal when the female pivot shape was changed. This indicates that hemolysis in monopivot pumps is mainly caused by shear stress between the male and female pivots.

Animals↗

Selective endothelin ET(B) receptor antagonist improves left ventricular function but exaggerates degeneration of cardiomyocytes in J2N-k hamsters.

BACKGROUND: Endothelin-1 (ET-1) receptor antagonist is expected to improve the prognosis of patients with heart failure, but the role of the ET(B) receptor in cardiac function and structure is complicated. In the present study the NADPH diaphorase activity and ET-1 content in the failing heart treated with ET(A) or ET(B) receptor antagonist were evaluated in a model of dilated cardiomyopathy. METHODS AND RESULTS: Selective ET(A) receptor antagonist, ABT-627 (10 mg/kg per day), or selective ET(B) antagonist, A-192621 (30 mg/kg per day), was given to 22-week-old J2N-k cardiomyopathic hamsters for 8 weeks. The effects of ABT-627 and A-192621 on cardiac function, left ventricular (LV) histology, ET-1 content and NADPH diaphorase activity in the LV were evaluated. Treatment with ABT-627, but not A-192621, significantly decreased ET-1 content and NADPH diaphorase activity. Although the improvement of LV function was modest, ABT-627 prevented tissue damage in J2N-k hamsters. In contrast, A-192621 worsened the degeneration of cardiomyocytes despite improving hemodynamic parameters. CONCLUSIONS: Selective ET(A) antagonist, but not ET(B) antagonist, reduced the ET-1 content as well as the NADPH diaphorase activity, and preserved the fine structure of LV myocardium in cardiomyopathic hamsters. Long-term blockade of ET(B) receptor might worsen the degeneration of cardiomyocytes through the ET-1/ET(A) system even if LV function could be improved.

Animals↗

QT PRODACT: sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation.

The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4x4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation.

Animals↗

[Cerebral hemodynamics in adult ischemic-type patients with moyamoya disease compared with those of atherothrombotic middle cerebral artery occlusion].

We measured regional cerebral blood flow (rCBF) in adult ischemic-type patients with moyamoya disease and in patients with atherothrombotic middle cerebral artery occlusion (MCAO) to investigate cerebral hemodynamics in adult ischemic-type of moyamoya disease. In this study we measured rCBF and regional cerebrovascular response (rCVR) using acetazolamide by Xenon-enhanced CT. Our subjects consisted of 15 adult ischemic-type patients with moyamoya disease and 27 atherothrombotic stroke patients with proximal occlusion of the middle cerebral artery. The region of interest was conducted in the anterior cerebral artery, middle cerebral artery and posterior cerebral artery territories as well as basal ganglia regions. rCBF was preserved in all regions of patients with moyamoya disease. However, rCVR severely decreased in the anterior circulation territory in patients with moyamoya disease compared with those of MCAO. These results suggest that rCBF in the anterior circulation territory of adult ischemic-type patients with moyamoya disease is preserved by vasodilation of the cerebral arteries, while cerebral hemodynamic reserve capacity is severely reduced. The results indicated that basal moyamoya vessels are dilated. These findings may be one of the reasons why stroke occurs more frequently in adult than child patients with moyamoya disease.

Adult↗

Role of endothelin ETB receptor in the pathogenesis of monocrotaline-induced pulmonary hypertension in rats.

We investigated the role of endothelin ETB receptor in the development of monocrotaline-induced pulmonary hypertension, by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the endothelin ETB receptor gene. Three weeks after injection of saline or monocrotaline (60 mg/kg, s.c.), hemodynamics, cardiac hypertrophy and endothelin-1 levels in right ventricle were determined. Monocrotaline produced a marked pulmonary hypertension associated with increases in right ventricular pressure and hypertrophy, pulmonary arterial medial thickening and the endothelin-1 levels. The monocrotaline-induced alterations tended to be enhanced in ETB-deficient homozygous rats, compared with cases in wild-type rats. The treatment with selective ETA receptor antagonist ABT-627 [2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid] for 3 weeks (10 mg/kg/day, twice daily) almost completely suppressed the monocrotaline-induced pulmonary hypertension and related organ damage both in ETB-deficient and wild-type animals to the same levels. Thus, we suggest that the antagonism of the ETA receptor is essential for the protection from monocrotaline-induced pulmonary hypertension, irrespective of the presence of the ETB receptors, although a protective role of ETB receptor-mediated action in the pathogenesis of this disease model cannot be ruled out.

Animals↗

Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension.

The functional roles of endothelin ETA and ETB receptors in the development of monocrotaline (MCT)-induced pulmonary hypertension were investigated using MCT-treated rats in the absence or presence of a daily administration of A-192621, a selective ETB receptor antagonist, ABT-627, a selective ETA receptor antagonist, or a combination of both drugs. Four weeks after the injection of saline or MCT (60 mg/kg, s.c.), cardiac hypertrophy, right ventricular systolic pressure and morphologic changes of pulmonary arteries were evaluated. Compared with the control animals, MCT produced marked pulmonary hypertension associated with increases in right ventricular pressure and hypertrophy, and pulmonary arterial medial thickening. These MCT-induced alterations were markedly suppressed by daily treatment with ABT-627 for 4 weeks (10 mg/kg/d, twice daily), whereas treatment with A-192621 significantly aggravated the above MCT-induced pathologic changes. The blockade of both receptor subtypes by a combination of A-192621 and ABT-627 also significantly improved the MCT-induced pathologic changes, to the same extent as with ABT-627 administration. Thus, an exaggerated response to MCT during ETB receptor blockade also seems to be mediated by ETA receptor activation, thereby suggesting that ETA receptor-mediated action is exclusively contributive to the pathogenesis of MCT-induced pulmonary hypertension, although we cannot rule out a protective role of ETB receptor-mediated action.

Administration, Oral↗

The most profitable use of flow visualization in the elimination of thrombus from a monopivot magnetic suspension blood pump.

The purpose of this study was to eliminate fluid dynamic causes of thrombus formation for the monopivot magnetic suspension centrifugal pump under development with the aid of flow visualization as an indirect measurement tool for animal experiments. The formation of thrombus observed in early animal experiments was successfully overcome by combining the multiple washout holes at the center into a single hole, optimizing the hole diameter, and eliminating the pivot gap. Flow visualization was used to optimize the washout hole diameter influencing the flow around the pivot. In animal experiments flow visualization showed that the contours of thrombus corresponded to shear rates of 300 s(-1) or 1300-1700 s(-1). It was found that flow visualization is a useful technique to predict locations where low shear thrombi form and to optimize the pump design in the development stage.

Animals↗

Intraoperative hemodynamic measurements of the vertebral artery and common carotid artery.

The hemodynamics in the vertebrobasilar artery (VBA) system were investigated in patients with vertebrobasilar insufficiency (VBI). Vertebral artery (VA) stump pressure and blood flows in the VA and common carotid artery (CCA) were intraoperatively measured in 45 patients who underwent surgical correction of the first segment of the VA (V1) for angiographic tortuosity, kinking, and/or stenosis manifesting as symptomatic VBI. The effects of changes in the systemic arterial blood pressure (SABP) induced by trimethaphan, phenylephrine, and cervical epidural anesthesia were also investigated. The VA stump pressure was 79.3 +/- 13.6 (mean +/- SD) mmHg and the ratio of the VA stump pressure to the SABP was 0.87 +/- 0.08. The baseline values were SABP 90.5 +/- 10.1 mmHg, VA blood flow 53.4 +/- 33.0 ml/min, and CCA blood flow 204.3 +/- 50.3 ml/min. During changes in the SABP, autoregulation of the blood flow in the VA appeared tighter than in the CCA. During cervical epidural anesthesia, blood flows in both the VA and CCA were significantly reduced in response to SABP reduction. This study demonstrated that the VBA system maintains excellent autoregulation with good collateral flows and cervical sympathetic nerve function. However, this autoregulatory capacity may be overwhelmed by unexpected occlusion of the VA due to postural changes associated with tortuosity, kinking, and/or stenosis of the V1 segment.

Adult↗

[Symmetrical bilateral epidural hematoma after head injury in the mid parietooccipital region: case report].

The authors presented a patient with acute symmetrical bilateral epidural hematomas, which are rare but life threatening. A 72-year-old male accidentally fell from the roof at a height of about 3 meters and hit his head against the ground. He was transferred to the emergency ward in our hospital. On admission, he was alert and had no neurological deficits. Skull X-ray film revealed a depressed fracture in the mid parietoocipital region and bilateral linear fractures extending from the parietal regions to the temporal regions. CT scan showed symmetrical bilateral epidural hematomas in the both parietotemporal regions. His consciousness deteriorated to be drowsiness about one hour after admission. An additional CT scan revealed enlargement of the both epidural hematomas and impending tentorial herniation. Therefore, an emergency operation was called for. For rapid decompression of the brain, bilateral craniotomies were carried out simultaneously by the two neurosurgeon-groups involved and bilateral epidural hematomas were also simultaneously removed. Injury of both of the middle meningeal arteries was revealed to be the cause of the bilateral epidural hematomas. Clinical course after operation was uneventful and the patient was discharged without any neurological deficit. Simultaneous bilateral craniotomies and removal of the epidural hematomas would have contributed to obtaining the good result in this patient.

Accidental Falls↗

Role of endothelin B receptor in the pathogenesis of ischemic acute renal failure.

This study evaluated the role of endothelin B (ET ) receptor-mediated action in the development and maintenance of ischemic acute renal failure (ARF), using the spotting-lethal ( ) rat that carries a naturally occurring deletion in the ET receptor gene. Because homozygous ( ) rats die shortly after birth due to congenital distal intestinal aganglionosis, genetic rescue of rats from the developmental defect using a dopamine-beta-hydroxylase (DbetaH)-ET transgene was performed to produce ET -deficient adult rats. Rescued homozygous (DbetaH-ET ) and wild-type (DbetaH-ET +/+) rats were subjected to ischemic ARF by clamping the renal pedicle for 45 min followed by reperfusion. At 24 h after the reperfusion, renal glomerular dysfunction and histologic damage, such as proteinaceous casts in tubuli, were markedly and observed equally in homozygous and wild-type groups, and these renal injuries gradually recovered. However, when the ischemia/reperfusion-induced renal injury was examined 7 days after the reperfusion, the recovery in homozygous ARF rats was obviously delayed compared with the wild-type animals. Two of the eight homozygous ARF rats died within 3 days after the reperfusion. Increment of renal endothelin-1 content after the ischemia/reperfusion was more marked in homozygous than in wild-type rats. Thus, ET receptor-mediated actions do not play an important role in the development of ischemic ARF but may be involved in the recovery process from ischemia/reperfusion-induced renal injury.

Acute Kidney Injury↗

[Drug sensitivity and beta-lactamase producibility of various types of bacteria clinically isolated during the period from December 1999 to February 2000].

beta-Lactamase activity and drug sensitivity were measured in 744 strains from 8 species of bacteria isolated at medical institutions in Chikugo District of Fukuoka Prefecture during the period from December 1999 to February 2000. Nitrocefin test revealed that beta-lactamase was positive in 48% of S. aureus, 7% of H. influenzae, and 92% of M. catarrhalis, and acidometry revealed that penicillinase/cephalosporinase were positive in 13%/14% of E. coli, 22%/8% of K. pneumoniae, 47%/97% of E. cloacae, 3%/65% of S. marcescens, and 10%/36% of P. aeruginosa. Based on the assessment of the MIC values of various types of antibacterial drugs for beta-lactamase-producing strains, there were 11 strains (1 strain of K. pneumonia, 6 strains of E. cloacae, and 4 strains of P. aeruginosa) of class-B beta-lactamase-producing bacteria out of a total of 496 strains of Enterobacteriaceae and Pseudomonas aeruginosa. The results of PCR analysis suggested that 1 strain of K. pneumonia, 1 strain of E. cloacae, and 4 strains of P. aeruginosa produced metallo-beta-lactamase. There was no strain (E. coli and K. pneumoniae) of ESBL-producing bacteria. BLNAR strains, on the other hand, were found in 9% (9/100) of H. influenzae.

Bacteria↗

Fractural characteristic evaluation of a microcapsule suspension using a rotational shear stressor.

We are developing microcapsule suspensions to evaluate the absolute hemolytic properties of centrifugal blood pumps. Four types of microcapsule suspensions, with maximum diameters of 100 microm or 10 microm, and membranes of polyurethane or melamine resin, were exposed to fluid dynamic shear up to 15,000 s(-1) with a rotating shear stressor developed in our laboratory. As a result, destruction was observed of only the 100 microm microcapsules. The microcapsules with polyurethane membranes broke at a high shear velocity range over 11,250 s(-1), a tendency similar to that observed using bovine blood. The microcapsules with melamine resin ruptured at approximately 7,500 s(-1). These observations could lead to determination of absolute hemolysis from shear stress occurring in centrifugal blood pumps.

Biomechanical Phenomena↗