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Biomedical subjects

S Eguchi

Publications and source records attributed to S Eguchi.

At least 163 records · Page 9Linked to original sources

Phenotypic change of endothelin receptor subtype in cultured rat vascular smooth muscle cells.

An endothelium-derived vasoactive peptide, endothelin (ET)-1, is a potent constrictor and mitogen for vascular smooth muscle cells (VSMC). To determine whether vascular ET receptor subtypes phenotypically change during in vitro culture conditions, we studied the expression of ET receptor subtypes, ET-induced phosphoinositide breakdown, and DNA synthesis in cultured rat VSMCs during serial passages. Binding studies using [125I]ET-1 as a radioligand revealed that the early passage (10th-15th) VSMCs possess predominantly ETA receptors, whereas the late passage (30th-35th) VSMCs possess predominantly ETB receptors in addition to ETA receptors. Northern blot analysis using cDNAs for rat ETA and ETB receptors as probes also demonstrated the predominant expression of ETA receptor mRNA in the early passage and ETB receptor mRNA in the late passage, whereas only ETA receptor mRNA was expressed in intact medium of rat aorta. ET-1 had a greater effect than ET-3 in stimulating inositol 1,4,5-trisphosphate formation, whereas ET-1 and ET-3 almost equipotently stimulated insitol 1,4,5-trisphosphate formation in the late passage VSMC even in the presence of an ETA receptor antagonist. ET-1-induced DNA synthesis was almost completely inhibited by an ETA receptor antagonist in the early passage VSMC. In contrast, ET-1, ET-3, and an ETB receptor agonist remarkably stimulated DNA synthesis in the late passage VSMC, which was completely inhibited by a nonselective ET receptor antagonist, but not by an ETA receptor antagonist. Our data provide the first evidence that a phenotypic change in VSMC in culture is concomitantly associated with a change in the ET receptor subtype that potentiates mitogenic activity and suggest that switching the ET receptor subtype from ETA to ETB during phenotypic change may in part contribute to the development of vascular lesions, such as in atherosclerosis.

Animals↗

Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells.

Vascular smooth muscle cells (VSMC) from rat aorta possess specific receptors for a novel potent vasorelaxant peptide, adrenomedullin (AM). To elucidate its receptor coupling to guanine nucleotide-binding stimulatory protein and the structural requirement of the AM molecule to its vascular receptors, we have studied the effects of guanine nucleotides on [125I]human (h) AM binding and adenylate cyclase activity in cultured rat VSMC, and the effects of various synthetic hAM analogs on [125I]hAM binding and the cAMP response. Guanosine 5'-O-(3-thiotriphosphate) dose dependently inhibited [125I]hAM binding to rat VSMC membranes. hAM stimulated adenylate cyclase activity, and its effect was additive with GTP. hAM-induced cAMP formation was abrogated by pretreatment with cholera toxin, but not by that with pertussis toxin. Intact hAM-(1-52)-NH2 and N-terminal truncated derivatives [hAM-(13-52)-NH2, hAM-(16-52)-NH2] almost equally inhibited [125I]hAM binding and stimulated cAMP formation, whereas removal of C-terminal Tyr52 residue [hAM-(1-51)-NH2] remarkably decreased receptor-binding activity and the cAMP response. The effects of hAM-(1-52)-OH, hAM-(1-51)-OH, and a linear hAM analog ([carbamoylmethyl-Cys16,21]hAM-NH2) were far less potent on receptor binding and the cAMP response than that of hAM-(1-52)-NH2. The C-terminal fragment [hAM-(33-52)-NH2] and the N-terminal fragment [hAM-(1-10)-OH] had neither receptor-binding nor adenylate cyclase activity. hAM-(22-52)-NH2 had no agonistic effect, but showed an antagonistic effect on the hAM-induced cAMP response. These data suggest that vascular AM receptors are functionally coupled to adenylate cyclase via guanine nucleotide-binding stimulatory protein. Studies of the structure-activity relationship of hAM revealed that the cyclic structure formed by the disulfide bridge and amidation of the C-terminal residue of the AM molecule are critical for receptor binding and subsequent cAMP generation and suggest that the C-terminal fragment hAM-(22-52)-NH2 may be an antagonist for vascular AM receptors.

Adenylate Cyclase Toxin↗

[The changes on cerebral hemodynamics during selective cerebral perfusion cooling].

We studied the influence on cerebral hemodynamics with 10 pigs, weighing 25 to 30 kg, when the temperature of perfusion blood changed in both rapid cooling and rewarming, and in slow them. As for the protocol of temperature, we decided that rapid change was the large temperature gradient of more than 0.5 degree C/min, and slow change was the small gradient of less than 0.3 degree C/min. Cardiopulmonary bypass (CPB) was established with a flow rate of 60 ml/kg/min, and core cooling was performed until the temperature of the returned blood from internal jugular vein reached 25 degrees C/min. For selective cerebral perfusion (SCP), blood was infused into aortic arch with the clamp of descending aorta at the temperature of less than 20 degrees C. We measured regional tissue cerebral blood flow (TCBF), intracranial pressure (ICP), carotid arterial flow (CAF), and carotid arterial pressure (CAP), and PCO2 in both CPB and SCP. Rapid cooling during CPB caused an elevation in CAP, and marked decrease in CAF, ICP, and PCO2. In contrast, rapid rewarming caused the significant increase in CAF, ICP. Slow change did not cause marked difference in CAP, CAF, and ICP, and PCO2. Moreover, TCBF was not significant in both rapid and slow changes. On the other hand, rapid change in SCP caused a significant decrease in CAP, significant difference in CAF, ICP. Slow change did not cause significant difference in them as same as in CPB. In conclusion, we presume that the influence on cerebral hemodynamics is less in slow cooling and rewarming than in rapid changes.

Animals↗

Effect of an AT1 receptor antagonist (CV-11974) on angiotensin II-induced cardiomyocyte hypertrophy in vitro.

Angiotensin (ANG) II, a potent vasoconstrictor is known to be a hypertrophic factor for cardiomyocytes. Recently, endothelin (ET)-1 has also been shown to be an autocrine/paracrine growth factor for cardiomyocytes. To determine the cellular mechanism by which ANG II induces cardiac hypertrophy, we studied the effects of ANG II on the gene expression of ET-1 and ET receptor subtypes (ETA, ETB), as well as its effects on the expression of immediate early oncogenes (c-fos, c-myc) in cultured rat cardiomyocytes in vitro. ANG II (10(-7) M) increased steady-state mRNA levels of ET-1 in the same manner as c-fos and c-myc during a short incubation period (0.5-1 h), while ANG II induced ETB receptor mRNA, but not ETA receptor mRNA, during a long incubation period (6-12 h). CV-11974, an antagonist of ANG II receptor type-1 (AT1), inhibited the ANG II-induced expression of c-fos, c-myc and ET-1 mRNAs, as well as that of ETB receptor mRNA, whereas PD-123319, an antagonist of the ANG II type-2 (AT2) receptor, failed to block such induction. CV-11974 similarly blocked ANG II-induced immediate-early oncogenes (c-fos, c-myc) in cultured rat vascular smooth muscle cells. Our findings indicate that ANG II immediately upregulates the cardiac ET-1 gene in the same manner as it does the immediate early protooncogenes, while the late induction of the ETB receptor, mainly via the cardiac AT1 receptor, suggests the involvement of endogenous ET-1 in ANG II-induced cardiac hypertrophy.

Angiotensin II↗

Noncontact, two-dimensional measurement of retinal microcirculation using laser speckle phenomenon.

PURPOSE: To report a new apparatus for noncontact, two-dimensional measurement of retinal microcirculation using the laser speckle phenomenon and to demonstrate that this apparatus can document known or expected changes in retinal blood flow. METHODS: The rabbit fundus was illuminated by an argon (blue) laser spot (0.62 x 0.62 mm), and its image speckle was detected with an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB), a quantitative index of blood velocity in the retinal microcirculation. The results were displayed on a color monitor showing the two-dimensional variation of the NB level in the measurement area. Using this apparatus in the rabbit, the NB in the retinal field free of visible surface vessels was determined and compared with the retinal blood flow rate measured using the microsphere technique in the same eye simultaneously. In addition, the effect of the ocular perfusion pressure (OPP) on NB was studied. In the above experiments, a stepwise reduction in OPP was introduced by elevating the intraocular pressure manometrically. RESULTS: The relative decrease in the average NB (NBav) over the field measured, with the reduction in OPP, showed significant correlation with the relative change in the blood flow rate determined using the microsphere technique (r = 0.59, P < 0.001). Although NBav in the retina was little affected by OPP change when OPP was greater than 50 mm Hg, NB decreased along with OPP at levels less than 50 mm Hg. CONCLUSIONS: The NBav showed significant correlation with the retinal blood flow rate determined with microsphere technique. Retinal microcirculation under various conditions can be studied two dimensionally and noninvasively in the living eye with the present apparatus.

Animals↗

[A new operative technique for pulmonary artery banding: adjustment of pulmonary artery bands by mitral valve flow velocity].

We developed a new technique to adjust the pulmonary artery band at surgery by monitoring the mitral valve flow velocity, which is indirectly indicative of the pulmonary flow. We employed this technique for 10 consecutive patients aged from 5 days to 5 months (mean, 1 months) weighing from 2.7 to 4.4 kg (mean, 3.3 kg). Underlying disease was aortic coarctation or interrupted+ventricular septal defect in 7 patients, single ventricule in 1 patients and miscellaneous defects in 2 patients. The pulmonary artery was exposed through a left lateral thoracotomy and a 3 mm wide Teflon tape was placed around the main pulmonary artery. The transducer of the Doppler echocardiography was placed along the left sternal border. The band was tightened gradually until the maximum velocity of the mitral valve flow decreased to around 70% of the previous level. During banding procedure, arterial oxygen saturation, heart rate and left ventricular contractility were monitored continuously. If bradycardia, unacceptable hypoxemia or ventricular dysfunction occurred, the band was released. The mitral valve flow velocity decreased rapidly by just a little additional tightness of the band between the range of 50% to 80% of the previous level. This technique enabled a very fine adjustment (less than 0.5 mm plication) and postoperative management has become very easy. Although there is a limitation of this technique that monitoring of the mitral valve flow velocity cannot be applied to the patients with significant interatrial shunt or mitral regurgitation, we conclude that this technique is simple and useful to obtain the optimum constriction of the pulmonary artery with excessive pulmonary blood flow.

Aortic Coarctation↗

[Tetralogy of Fallot with a restrictive ventricular septal defect caused by a membranous flap].

A 5-year-old boy who had typical tetralogy of Fallot (TOF) with mild cyanosis was referred to us. Preoperative echocardiogram revealed that in addition to the TOF morphology, an abnormal piece of tissue attached to the right side of the ventricular septum was floating and obstructing flow through the ventricular septal defect (VSD) in systole. Preoperative cardiac catheterization showed suprasystemic right ventricular pressure with a gradient of 60 mmHg between the right ventricle and the aorta, and a right ventriculogram demonstrated a narrow radiolucent structure beneath the aortic valve in the right ventricle. During surgery a fibrous membranous tissue, with no relation to the tricuspid valve, was found to extend from the edge of the VSD to the aortic valve and to partially occlude the defect. This tissue was used as a suture anchorage for patch closure of the defect. Preoperative echocardiography is useful to detect such flaps and early surgical correction should be done to prevent right ventricular failure resulting from right ventricular pressure overload.

Child, Preschool↗

Long term clinical results with 19 mm or 21 mm standard aortic St. Jude Medical prosthesis.

Comparison of long term clinical results after aortic valve replacement with 19 mm or 21 mm vs. 23 mm or larger bileaflet prostheses has not yet been reported. Between December 1979 and September 1993, 80 consecutive patients who underwent isolated aortic valve replacement at Niigata University using a standard St. Jude Medical valve were assigned to small size group (19 mm and 21 mm, n = 34) or to large size group (23 mm or larger, n = 46). In the small size group, patient's age was older, body surface area smaller, female patients and calcified aortic stenosis were dominant (all p < 0.01). The left ventricular systolic dimension was shorter (p < 0.001), while the cardiothoracic ratio was similar to that of the large size group. All patients received warfarin treatment, and target thrombotest level was 15 to 25% (equivalent to INR 1.6 to 2.1). Actuarial survival rates including hospital death in the small size group (94% at fifth postoperative year) were comparable to those in the large size group. Cerebrovascular event occurred in two patients with the small size prosthesis (1.3%/pty) and three with larger prosthesis (0.9%/pty). Major hemorrhagic complication was not observed in either group. No significant difference was noticed in the proportion free from valve-related morbidity. In the patients with aortic stenosis (n = 41), the left ventricular posterior wall thickness decreased from 15 mm preoperatively to 11 mm late post surgery in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Adjustment of pulmonary artery banding by mitral valve flow velocity.

In order to determine the tightness of the pulmonary artery band, Doppler echocardiography is used to assess mitral valve flow velocity, which is an indirect indicator of pulmonary blood flow. The band is tightened until the velocity decreases to 70% of the original maximal level. Additional adjustment of the constriction is then made to obtain reasonable arterial oxygen saturation, heart rate and ventricular contractility. Using this method, 12 consecutive patients underwent pulmonary artery banding with satisfactory results. This technique is simple but useful in obtaining optimum constriction of the pulmonary artery in congenital heart disease with excessive pulmonary blood flow.

Aorta, Thoracic↗

[The protective effect and problem of retrograde cerebral perfusion].

In order to study the protective effect and problem of retrograde perfusion (RCP), cerebral hemodynamics and cerebral metabolism were evaluated in fourteen pigs weighing 25-30 kg. Intracranial pressure, carotid arterial flow and pressure, and internal jugular venous pressure as cerebral hemodynamics; pyruvate, lactate, and oxygen consumption as cerebral metabolism; and brain temperature were measured. The animal was cooled to electrical cerebral silence on electroencephalogram under cardiopulmonary bypass. Then, animals were divided into three groups: group I (n = 4); circulatory arrest; group II (n = 3); RCP through superior vena cava (SVC); group III (n = 7); RCP through bilateral internal jugular vein (IJV). Retrograde perfusion flow was regulated to maintain the SVC pressure or IJV pressure of 30 mmHg, for 90 minutes. The variations in brain temperature were least in group III. As perfusion flow increased, intracranial pressure, and inferior vena cava (IVC) pressure increased. But, cerebral perfusion pressure, which was calculated from the difference of intracranial arteriovenous pressure, did not increase and, SVC pressure and returned blood flow through the aorta did not increase in group III. In group II, there was no significant relation between pump flow, SVC pressure, and intracranial pressure, but SVC pressure had a positive correlation with the pressure gradient of SVC-IJV. The uptake of cerebral lactate, cerebral pyruvate, and lactate-pyruvate ratio, and cerebral oxygen consumption were superior in group III than other groups. In conclusion, RCP through IJV was advantageous to maintain hypothermia and aerobic metabolism of the brain during systemic hypothermic circulatory arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Successful primary correction for tetralogy of Fallot associated with total anomalous pulmonary venous drainage (type Ia)].

The surgical correction was performed successfully in a 3-year-old girl with tetralogy of Fallot associated with total anomalous pulmonary venous drainage (type Ia). The preoperative cardiac catheterization and angiography showed high systolic pulmonary artery pressure (58 mmHg) and small left ventricular volume (54% of normal). The early postoperative course was stormy because of the unstable circulatory state. During the early postoperative period, we estimated the volume of left ventricle by 2 D echocardiography. A significant increase of the volume was observed on the 8th postoperative day, when her circulatory state became stable. The cardiac catheterization before discharge revealed Pp/Ps of 0.38 and normal LV volume. We conclude that primary repair should be done for this combined cardiac anomaly, even if small left ventricle and pulmonary hypertension is present.

Female↗

[An apparatus using the laser speckle phenomenon for non-invasive two-dimensional analysis of retinal microcirculation].

A new instrument using the laser speckle phenomenon for non-invasive two-dimensional analysis of the retinal microcirculation was developed. The fundus was illuminated with an argon laser spot and its image speckle was detected with an area sensor. The difference between the average of output data (Imean) and output data for successive scannings of the image speckles at the sensor plane was calculated and integrated to give Dmean, and Imean/Dmean is defined as normalized blur (NB), which is a quantitative index of blood flow velocity. The results were displayed in color graphics showing the two-dimensional variation of the NB level in the area of interest. The NB had a good correlation with the speed of rotation of the ground glass in a range between 5 and 120 mm/sec. Using this instrument, the effect of intraocular pressure (IOP) on the microcirculation of the rabbit retina was studied. The coefficient of reproducibility was 9.2% when measured in the same area twice at 5-minute intervals. A stepwise reduction in the ocular perfusion pressure (OPP) was introduced by elevating the IOP manometrically. The NB in the retina was little affected by OPP change when OPP was above 50 mmHg, but below this value the NB decreased as the OPP decreased.

Animals↗

[Noninvasive two-dimensional analysis of microcirculation in optic nerve head and choroid--calibration of the normalized blur (NB) value].

We have developed an apparatus using the laser speckle phenomenon for noninvasive two-dimensional measurements of the fundus microcirculation. The normalized blur of the speckle pattern (NB value) was adopted as an index of blood flow velocity in the tissue. The present study investigated whether the NB value can be also used as a quantitative index of the blood flow rate in the tissue. In experimental animals, an injection of a lethal dose of pentobarbital causes rapid reduction in the ocular perfusion pressure (OPP), which linearly correlates with blood flow rate in the ocular tissue. The NB in rabbit optic nerve head (ONH) tissue showed a linear correlation (r = 0.98, p < 0.001) with the OPP after injection of a lethal dose of pentobarbital, which suggested that the NB value parallels the blood flow rate in the ONH tissue. At various levels of OPP, the choroidal NB showed a good correlation (r = 0.60, p < 0.001) with the choroidal blood flow rate measured with microsphere technique. These results indicated that the NB value can be used as a quantitative index not only for the blood flow velocity but also for the blood flow rate in the tissue.

Animals↗

[Noninvasive two-dimensional analysis of retinal microcirculation using the laser speckle phenomenon--II. Comparison of results with those obtained with the microsphere technique].

We have recently developed an apparatus for noninvasive two-dimensional analysis of the retinal microcirculation using the laser speckle phenomenon. The fundus is illuminated by an argon laser spot and its image speckle is detected by an area sensor. The difference between the average of output data and the output data for successive scannings of the image speckles at the sensor plane is calculated to give the value of normalized blur (NB), which is a quantitative index of tissue blood flow velocity. In pigmented rabbit eyes, the coefficient of reproducibility was 8% when the same area of retina was measured twice at 5-minute intervals and 13% at 24-hour intervals. The NB values in the retina free of visible vessels were recorded under various levels of intraocular pressure ranging from 10 to 80 mmHg and the results were compared with the blood flow rate determined with the colored microsphere technique. A linear correlation was found between the former and the latter, which suggested that the NB value also parallels the tissue blood flow rate.

Animals↗

[The study on cerebral hemodynamics during selective cerebral perfusion].

This study was undertaken to clarify characterization on cerebral hemodynamics during deep hypothermic selective perfusion (SCP) in 18 pigs. Besides, the changes on cerebral hemodynamics were investigated with obstruction to venous drainage due to the clamp of superior vena cava (SVC) cannula. For SCP, blood was infused into aortic arch with the clamp of descending aorta, during 90 minutes at 20 degrees C. We measured regional cerebral blood flow (CBF), intracranial pressure (ICP), and carotid arterial flow (CAF), and carotid arterial pressure. The carotid arterial pressure as perfusion pressure was not significantly correlated with CAF, CBF and ICP. Although CAF increased as pump flow rate increased, the relationship between pump flow and CBF was not significant. Moreover, SVC pressure showed a tendency to increase, as CAF increased. Both ICP and internal jugular vein pressure (IJVP) were significantly (p < 0.01) increase, and CAF was significantly (p < 0.05) decrease with the clamp of SVC cannula. On the other hand, both ICP and IJVP were significantly decrease, and both CAF and CBF were increase, without unclamp of SVC cannula. The results suggest that cerebral autoregulation is intact during deep hypothermic SCP, and hyperperfusion cause the increase of shunt flow in extracranial area, and besides, the increase of ICP with obstruction to venous drainage cause decrease in cerebral blood flow.

Animals↗

[Effect of calcium antagonist on retinal microcirculation evaluated with the laser speckle retinal microcirculation analyzer].

The effect of intravenous administration of a calcium antagonist on the retinal microcirculation in rabbit eyes was examined with a laser speckle retinal microcirculation analyzer. Under general anesthesia, 40 micrograms/kg of nicardipine, a calcium antagonist, was injected intravenously in the nicardipine group, and 0.4 ml/kg of saline in the control group. A quantitative index of blood flow velocity, the normalized blur (NB) value, in a retinal area (0. 62 x 0.62 mm) free of visible vessels, was recorded at 1-minute intervals for the first 5 minutes and at 5 minute-intervals for the next 85 minutes. The retinal NB value in the nicardipine group was significantly greater than in the control group, averaging 119%, 115%, 111%, 112%, and 116% of the initial value at 65, 75, 80, 85, and 90 minutes after injection, respectively. The blood pressure in the nicardipine group decreased significantly from 1 to 20 minutes after injection. The pulse rate, arterial pH, partial CO2 pressure, partial oxygen pressure, body temperature and intraocular pressure did not show significant change during the experiment. These results suggest, for the first time, that nicardipine increases the blood flow velocity in the retinal microvasculature in the living eye.

Animals↗