Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 55 records · Page 3Linked to original sources

PubMed1994

Simulation study on heart failure: effects of contractility on cardiac function.

Using the model proposed by Beyar and Sideman, the effect of maximum isometric active stress at optimal sarcomere length (sigma 0) on left ventricular (LV) function was examined. Comparing the results of calculated LV function with those of reported experiments, sigma 0 was shown to be a potential indicator of myocardial contractility, and the model of Beyar and Sideman successfully predicted LV function with various myocardial contractilities. The LVP compensation curve, which describes the relationship between sigma 0 and maximum LV pressure, was then hypothesized. The combination of the Beyar-Sideman model and the LVP compensation curve enabled the prediction and approximation of the actual process of deterioration in heart failure. These models represent a step towards a fundamentally new concept in the current clinical situation of compensated heart failure and also in evaluating the process of heart failure.

Computer Simulation↗

PubMed1994

Simulation study on the effect of external vibration on left ventricular function: potential indicator of LV tolerance to the sudden reduction of myocardial contractility.

In a previous study the authors reported that external mechanical vibration applied to the left ventricular (LV) epicardium induces contractility-dependent depression in LV pressure, stroke volume and stroke work. It was suggested that this depression may be caused by the direct effect of external vibration on contractile protein. In another paper in this issue, it is proved that LV function with various myocardial contractilities and the actual process of deterioration in heart failure are well simulated in the model proposed by Beyar and Sideman, after some modifications have been made. In the study reported here it is assumed that an external mechanical vibration induces sudden reduction in myocardial active stress in the model of Beyar and Sideman; in this way the contractility-dependent effect of external vibration on LV function has been simulated. The results of this simulation support the suggestion that external mechanical vibration directly affects contractile protein and reduces LV function, and it is further suggested that the reduction of LV function induced by external vibration reflects the reserve or tolerance capacity of LV to a sudden reduction of myocardial contractility.

Animals↗

PubMed1994

Effects of ryanodine on development of myogenic response in rat small skeletal muscle arteries.

OBJECTIVE: The aim was to elucidate the functional role of the sarcoplasmic reticulum in myogenic contraction. METHODS: Small arteries which perfuse the rat gracilis muscle were isolated and cannulated. The inner diameter was measured under no flow condition. Myogenic contraction was induced by increasing transmural pressure from 40 to 100 mm Hg. The diameter transient and the steady state internal diameter were analysed at 40 (ID40) and 100 mm Hg (ID100) of lumen pressure. RESULTS: In control, the vessels dilated immediately after the pressure change, and then constricted over approximately 4 min (the diameter decay). ID40 and ID100 were 120(SEM 16) and 108(12) microns (n = 6, p < 0.05), respectively. Ryanodine (10(-5) M) decreased ID40 to 82(8) microns. The relative rate of the diameter decay in the first 1 min was lower in the ryanodine treated vessels than in control, at 43(1)% v 74(7)%, n = 6 (p < 0.05). While KCl constriction was similar to that of ryanodine, the diameter decay was identical to that of control. Thus a decrease in baseline diameter was not of itself the cause of the depressed rate of diameter decay in the ryanodine treated vessels. Nisoldipine (10(-6) M) abolished myogenic contraction. CONCLUSIONS: Ryanodine sensitive sarcoplasmic reticular function is probably involved in the mechanism for developing the myogenic response in rat skeletal muscle small arteries.

Animals↗

PubMed1994

Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea.

BACKGROUND: It has previously been reported that short term submental stimulation can reduce the frequency of apnoea and improve sleep architecture in patients with obstructive sleep apnoea. The effects of submental stimulation during consecutive nights on apnoea or on daytime sleepiness have not, however, been studied. METHODS: Patients with obstructive sleep apnoea were studied by polysomnography on a control night, for five consecutive nights of submental stimulation, and on three following nights (n = 8). A multiple sleep latency test (MSLT) (n = 8) and measurement of the upper airway resistance (n = 5) were performed during the day after the polysomnographic study, on the control night, and on the fifth stimulation night. In an additional five patients with obstructive sleep apnoea, matched for age, sex, and weight, the effects of two nights of stimulation were examined for comparison. Submental stimulation began when an apnoea lasted for five seconds and stopped with the resumption of breathing as detected by oronasal flow. RESULTS: The apnoea index, the number of times per hour that SaO2 dropped below 85% (SaO2 < 85%/hour), and the total apnoea duration expressed as a percentage of total sleep time during stimulation nights decreased to approximately 50% of the corresponding values on the control night. This improvement persisted for at least two nights after the five consecutive stimulation nights, but not after the two consecutive stimulation nights. Sleep architecture and MSLT following the stimulation nights improved but upper airway resistance did not change. CONCLUSIONS: Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing.

Adult↗

PubMed1994

Effect of an oral gold compound, auranofin, on non-specific bronchial hyperresponsiveness in mild asthma.

BACKGROUND: A recent double blind clinical trial in Japan has shown that auranofin (6 mg/day) is a useful treatment for patients with moderate to severe asthma. To investigate the mechanism of action of auranofin the bronchial responsiveness to inhaled methacholine has been studied in well controlled asthmatic subjects. METHODS: Nineteen adult asymptomatic asthmatic subjects received auranofin (3 mg orally twice a day) or inactive placebo in random order for 12 weeks in a double blind fashion. Bronchial responsiveness to inhaled methacholine and pulmonary function tests were measured at the same time on different days before, and six and 12 weeks after, each treatment. RESULTS: Non-specific bronchial hyperresponsiveness 12 weeks after treatment with auranofin was decreased compared with that before treatment with auranofin and 12 weeks after treatment with inactive placebo, although the treatment did not improve pulmonary function tests. CONCLUSIONS: Non-specific bronchial hyperresponsiveness 12 weeks after treatment with auranofin is decreased in a group of mild asymptomatic asthmatic patients with normal lung function.

Adult↗

PubMed1994

Noninvasive measurement of left ventricular myocardial elasticity.

We examined Advani and Lee's equation (ALeq) and a dimension analysis-derived equation (DAeq), both of which treat vibration of the elastic spherical shell and are able to estimate elasticity of the shell noninvasively when the sizes and eigen-frequency are provided. We confirmed that ALeq was numerically identical to DAeq and that both equations gave the precise elasticity of the silicone shell. Then we estimated left ventricular (LV) myocardial elasticity noninvasively at the moment of the first heart sound emission (1HS) in 25 healthy subjects and 14 hypertrophic cardiomyopathy (HCM) patients, based on the LV eigen-frequency detected by an intraesophageal miniature vibration sensor. HCM patients had a higher mean value of LV myocardial elasticity at 1HS than healthy subjects [102.3 +/- 33.4 vs. 70.7 +/- 24.4 kPa, P < 0.01 (Pa = N/m2 = 10 dyn/cm2)]. We thereby demonstrated the possibility of a noninvasive estimate of myocardial elasticity.

Adult↗

PubMed1994

Effects of aging on induction of cardiocyte growth by extracardiac factors.

To examine the effect of aging on the induction of cardiac myocyte growth by extracardiac factors, we cultured myocytes obtained from neonates of the same litter and implanted them into the peritoneal cavity of developmental phase (2-mo-old), young adult (7-mo-old), and aged (18-mo-old) host Wistar rats. Hearts obtained from 2- to 4-day-old neonates were dissociated with gentle trypsinization, and cells were seeded in culture wells and inserts. The culture insert (9 mm in diam) has a thin membrane the pore size of which is 0.45 microns. After 24 h of usual extracorporeal incubation in the serum-supplemented medium, the inserts were implanted into the peritoneal cavity of the host rats of the three age groups. Zero, 24, 72, and 96 h after implantation into the peritoneal cavity, the inserts were removed from the peritoneal cavity. Surface area of plated myocytes, diameter, number, protein, and DNA content of the suspended cells were measured. Size, protein content per cell, and protein per DNA of cells implanted into the peritoneal cavity were significantly greater than those cultured in the usual extracorporeal method. Growth of the myocytes cultured in the peritoneal cavity of aged host rats was significantly less compared with that of myocytes implanted in the peritoneal cavity of younger rats. Thus aging attenuates the induction of cardiac myocyte growth by extracardiac factors.

Aging↗

PubMed1994

Apically localized IP3 receptors control chloride current in airway gland acinar cells.

We examined the role of inositol 1,4,5-trisphosphate (IP3) receptors in acetylcholine (ACh)-induced chloride (Cl-) current in acinar cells of human and feline airway submucosal glands, using whole cell patch-clamp analysis. ACh (10 nM-1 microM) induced an initial Cl- current followed by a K+ current, and lower doses of ACh (1-10 nM) often induced oscillations of both currents, which were mimicked by the application of intracellular IP3. Neither isoproterenol (-10 microM) nor raising intracellular adenosine 3,5-cyclic monophosphate induced any current. Caffeine (20-50 mM) and intracellular ryanodine (1-100 microM) induced a K+ current alone without Cl- current. Monoclonal antibodies to the IP3 receptor abolished both ACh-induced K+ and Cl- currents. Immunohistochemical analysis revealed the localization of IP3 receptors on both the cytosol and some regions of the endoplasmic reticulum beneath the apical membrane of acinar cells. These results indicate that apically localized IP3 receptors control Cl- secretion from airway submucosal gland cells.

Acetylcholine↗

PubMed1994

Extracellular ATP regulation of feline tracheal submucosal gland secretion.

The standard patch-clamp technique was employed on enzymatically digested acinar cells of submucosal glands isolated from feline trachea. ATP (-10(-3) M) evoked bidirectional current responses and an initial inward current at -80 mV (Cl- current) was followed by an outward current at 0 mV of membrane potential (K+ current). Isoproterenol (ISO) alone did not evoke any significant current responses. However, ISO augmented the ATP-induced inward and outward currents. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, mimicked the augmentation by ISO. [Ca2+]i of acinar cells in isolated gland was measured using a fluorescent dye, fura 2. ATP (-10(-3) M) induced an immediate increase in [Ca2+]i followed by a prolonged plateau, and Ca2+ removal resulted in an initial increase alone without the prolonged phase. ISO also augmented the ATP-evoked increases in [Ca2+]i mainly in the plateau phases. Mucus glycoprotein (MGP) secretion was estimated by measuring trichloroacetic acid-precipitable [3H]glycoconjugates from isolated glands. ATP (-10(-3) M) evoked significant MGP secretion and ISO enhanced the ATP-induced MGP secretion. In contrast, adenosine (-10(-3) M) produced no significant responses in current, MGP secretion, or [Ca2+]i. These findings suggest that 1) P2-receptor stimulation and the resultant [Ca2+]i rise induced both electrolyte and MGP secretions and 2) ATP-induced secretion is enhanced by an adenosine 3',5'-cyclic monophosphate intracellular concentration [cAMP]i-rise after beta-receptor stimulation in airway submucosal glands.

Adenosine Triphosphate↗

PubMed1994

An expectorant, stepronin, reduces airway secretion in vitro.

Stepronin (SPN) is clinically used as an expectorant, and thenoic acid (TA) is its metabolite. We examined the effects of these drugs on the bioelectric parameters [potential difference (PD), short circuit current (SCC), conductance (G)] of the posterior epithelial membrane of canine trachea and on those of the mucus glycoprotein secretion from feline tracheal isolated glands. PD and SCC were obtained using an Ussing chamber and G was calculated as the ratio SCC/PD. Neither SPN nor TA significantly altered the baseline values of PD and SCC. However, in the mucosal solution, both SPN and TA significantly inhibited PD and SCC evoked by isoproterenol (ISOP), whereas G remained unchanged. Amirolide did not alter the inhibitory action of SPN and TA. Mucus glycoprotein secretion from isolated glands was estimated by measuring trichloride acetic acid-precipitable [3H]-glycoconjugates. SPN and TA significantly reduced mucus glycoprotein secretion. Further, when stimulated by methacholine, these agents significantly inhibited mucus glycoprotein secretion from isolated glands. These findings suggest that SPN inhibits airway secretion in vitro by both decreasing Cl- secretion from epithelial cells and mucus glycoprotein secretion from submucosal glands.

Amiloride↗

PubMed1994

Possible mechanisms of airway hyperresponsiveness after late asthmatic response in guinea pigs.

To elucidate the mechanism of airway hyperresponsiveness after late asthmatic response (LAR), we analyzed bronchoalveolar lavage fluid (BALF) and examined the airway smooth muscle contractility to acetylcholine (ACh). On day 1 after LAR, there was a significant positive correlation between the number of neutrophils in BALF and the increase in airway responsiveness after LAR (r = 0.82, p < 0.01). In the in vitro study, the dose response curve to ACh was significantly shifted to the left after removal of the epithelium in control guinea pigs. However, in hyperresponsive animals after LAR, removal of the epithelium had no significant effect on ACh-induced response. These results indicate that infiltration of neutrophils and other inflammatory cells induce epithelial damage and hence the development of airway hyperresponsiveness after LAR.

Acetylcholine↗

PubMed1994

Effect of calcitonin gene-related peptide on coronary microvessels and its role in acute myocardial ischemia.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent dilator of epicardial conduit vessels and is released during myocardial ischemia in humans. However, the effect of CGRP on coronary arterial microvessels is still unclear, and it is unknown if CGRP modulates the tone of coronary arterial microvessels during acute myocardial ischemia. METHODS AND RESULTS: Epimyocardial microvessels were observed through a microscope equipped with a floating objective system in anesthetized open-chest dogs. Heart rate and aortic pressure were maintained at control levels. Flow velocity of the left anterior descending coronary artery (LAD) was measured with a suction-cup Doppler probe. When CGRP was cumulatively infused into the LAD (0.05, 0.5, 5.0, and 50 pmol/kg per minute) or superfused (0.03, 0.3, 3.0, and 30 nmol/L) over the left ventricular surface, arterial control microvessels > 100 microns in diameter dilated dose dependently at dosages of 0.5 to 50 pmol/kg per minute (infused) or 0.3 to 30 nmol/L (superfused), but those < 100 microns dilated only at the highest dose, and those > 100 microns had greater dilation in both groups. Only the highest dose of CGRP (infused) significantly increased coronary flow. The superfusion of CGRP(8-37) (CGRP receptor antagonist, 300 nmol/L) did not affect the control diameters of coronary arterial microvessels but completely abolished CGRP-induced vasodilation at the same doses (infused and superfused). However, 300 nmol/L of CGRP(8-37) did not affect the response of coronary arterial microvessels to the LAD occlusion in any size. CONCLUSIONS: CGRP preferentially dilates the coronary arterial microvessels > 100 microns in diameter but has only a small effect on those < 100 microns. Endogenous CGRP does not modulate the tone of coronary arterial microvessels during acute myocardial ischemia in beating canine hearts.

Animals↗

PubMed1994

Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma.

To investigate whether increased release of acetylcholine may be involved in propranolol-induced bronchoconstriction (PIB), the inhibitory effect of pilocarpine (Pilo), an agonist of M2-muscarinic receptors that in 11 stable asthmatic subjects. The bronchial responsiveness to Pilo was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase. In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalation for 1 min was measured. Atropine reversed PIB. After pilocarpine pretreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs decreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/- SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pilo to PIB without Pilo correlated inversely according to the pretreatment dose (Dmin) of Pilo (p < 0.05). These results suggest increased release of acetylcholine in PIB and that M2-muscarinic receptors are at least in part functioning in stable asthmatic airways.

Acetylcholine↗

PubMed1994

Bradykinin-induced airway inflammation. Contribution of sensory neuropeptides differs according to airway site.

We examined the mechanisms of bradykinin-induced airway microvascular leakage in guinea pig airways by measuring extravasation of Evans blue dye. Animals were pretreated with propranolol (1 mg/kg, intravenous) and atropine (1 mg/kg, intravenous) to block the beta-adrenergic and muscarinic responses, respectively. Bradykinin (250 nmol) instillation into airways significantly increased the leakage of dye in the trachea, main bronchi, and intrapulmonary airways to the same degree. The bradykinin B2-receptor antagonist HOE140 (500 nmol/kg, intravenous) did not alter basal leakage but almost completely inhibited bradykinin-mediated leakage. By contrast, the neurokinin NK1 antagonist FK888 (10 mg/kg, intravenous) partially inhibited bradykinin-induced leakage in trachea (p < 0.01) and main bronchi (p < 0.01), but had no significant effect on intrapulmonary airways. Indomethacin (5 mg/kg, intravenous) had no effect on the plasma leakage after instilled bradykinin. We concluded that the airway inflammatory response to bradykinin administered directly into the airways is mediated by bradykinin B2 receptors and partially mediated by tachykinin release from sensory nerve terminals, whereas cyclooxygenase products have no important role in the response. In the central airways, the contribution of sensory neuropeptides to the bradykinin response is greater than that caused by direct stimulation of the B2 receptor on the endothelium at the postcapillary venule of the bronchial circulation. In contrast, in the peripheral airways, the contribution of direct B2-receptor stimulation on the airway vasculature is greater than that involving sensory neuropeptides.

Animals↗

PubMed1994

Accumulation of basophils and their chemotactic activity in the airways during natural airway narrowing in asthmatic individuals.

To investigate cellular differentials in natural airway narrowing of steroid-dependent asthmatic individuals, we performed bronchoalveolar lavage (BAL) on 10 inpatients with asthma treated only with bronchodilators during episodes of natural airway narrowing evaluated by serial monitoring of peak expiratory flow (PEF), and on nine normal volunteers. We confirmed that the airway narrowing was not completely reversed by salbutamol aerosol just before the BAL study, but was completely reversed by administration of systemic steroid after the BAL study. Thus, the natural airway narrowing investigated in this study consisted not only of the constriction of airway smooth muscle, but also of edema of the airway mucosa and/or secretion in airways. Both the numbers and percentages of eosinophils and alcian blue-positive cells in BAL fluids from the asthmatic subjects were significantly higher than those of normals, but the numbers and percentages of neutrophils, lymphocytes, and macrophages were not. Thus, eosinophils and alcian blue-positive cells selectively increased in the airways during the natural airway narrowing. Because we found that the metachromatic cells consisted of two types, with a single nucleus and with segmented nuclei, we further examined basophil chemotactic activity (BCA) in BAL fluids. We showed that BCA was significantly higher in the asthmatic (79.3 +/- 17.2 cells/5 hpf) than in the normal subjects (6.2 +/- 1.6 cells/5 hpf), and also that the activity was more strongly correlated with the cells having segmented nuclei (p = 0.95) than with all of the cells (p = 0.73).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Effects of prostaglandin E2 inhalation on hypercapnic response in normal subjects.

It is known that the ventilatory response to carbon dioxide (CO2) is increased in asthmatics with airway obstruction. Increased vagal afferent activity as well as increased airway resistance have been postulated as the causative mechanisms. However, whether increased vagal afferent activity without bronchoconstriction increases the ventilatory response to CO2 has not been investigated in humans. We examined the effects of prostaglandin E2 (PGE2) inhalation, which is known to stimulate vagal afferent receptors in the lung without an increase in airway resistance, on the respiratory response to CO2 in seven healthy male subjects. Either physiologic saline or PGE2 (100 micrograms/ml) was inhaled through a Bird nebulizer for 3 min. Twenty minutes after each inhalation, the responses of minute ventilation (VE) and occlusion pressure (P0.1) to hyperoxic hypercapnia were measured. Both the relationships between VE and P0.1 to an increase in tension of end-tidal CO2 (PETCO2) were analyzed by linear regression. Although the mean value of respiratory resistance after PGE2 (3.0 cm H2O/L/s +/- 0.4) did not differ significantly from that after saline (3.1 cm H2O/L/s +/- 0.4), inhaled PGE2 significantly increased the hypercapnic response. This result suggests that the increased vagal afferent activity per se plays an important role in increasing the hypercapnic ventilatory response in humans.

Administration, Inhalation↗

PubMed1994

Mathematical model of the effects of mechanical vibration on crossbridge kinetics in cardiac muscle.

We previously reported that the application of an external mechanical vibration to the epicardial surface caused a vibration-induced-depression (VID) of left ventricular (LV) function. The magnitude of the VID of peak LV pressure increased as either the amplitude or the frequency of the vibration increased. When LV contractility was altered by the administration of propranolol or by continuous infusion of dobutamine, the magnitude of the VID of peak LV pressure was inversely correlated with LV contractility. These characteristics were observed in open-chest and isolated canine preparations. In the present study, we constructed a muscle model to obtain a theoretical explanation for these effects. This model was first proposed by Gray, Gonda and Cheung, and has been extended in this report to explain twitch tension. This new, improved model is able to explain twitch tension and the effects of external vibration on twitch contraction semi-quantitatively. The successful predictions of the this model support the idea that external vibration directly affects contractile protein and modulates crossbridge kinetics.

Adenosine Triphosphatases↗

PubMed1994

Bronchorrhea from diffuse lymphangitic metastasis of colon carcinoma to the lung.

Bronchorrhea, defined as watery sputum of 100 ml or more per day, was seen in a 52-year-old female patient with diffuse lymphangitic metastasis of colon carcinoma to the lung. For 5 months before the visit to our clinic, she complained of progressive worsening of the cough, watery sputum, and shortness of breath. On admission to our hospital, she expectorated large amounts of nonpurulent watery sputum (150 to 300 ml/d), and showed diffuse reticular and linear shadows in both lungs on chest radiograph and severe obstructive impairment (FEV1 percent, 35 percent) in lung function tests. Histologic findings obtained from both surgical specimens at abdominal operation for ileus and lungs at the autopsy revealed lymphangitic metastasis of ascending colon carcinoma to the lung. At autopsy, histologically the lungs showed diffuse infiltrations of mucus-secreting adenocarcinoma cells to both lung parenchyma and airway submucosa.

Adenocarcinoma, Mucinous↗