PubMed Health⌕ Search

Biomedical subjects

T Ohrui

Publications and source records attributed to T Ohrui.

16 recordsLinked to original sources
PubMed1992

Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat airways.

To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.

Alprostadil↗
PubMed1992

Vascular permeability and airway narrowing during late asthmatic response in dogs treated with Metopirone.

Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR (P greater than 0.10), but in LAR, it increased significantly from that of control (p less than 0.01) and IAR (p less than 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 microns) in the trachea, large (diameter, greater than 5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi (p less than 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge (p less than 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.

Airway Obstruction↗
PubMed1992

Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure.

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.

Adult↗
PubMed1992

Capsaicin desensitization inhibits cigarette smoke-induced increase in cytoplasmic motility of alveolar macrophages in guinea pigs.

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in guinea pigs with and without systemic capsaicin pretreatment in vivo. Four days after instillation of 3 mg/kg ferrimagnetic particles (Fe3O4) into the trachea, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time because of particle rotation (relaxation), which is thought to be correlated to CM of AM. The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to baseline values within 5 min, and with the inhalation of the smoke of as many as three cigarettes, peak lambda 0 increased in animals without capsaicin pretreatment. However, cigarette smoke decreased lambda 0 with an increased number of cigarettes in animals with capsaicin pretreatment. Injection of nicotine or acetylcholine increased respiratory resistance to a degree similar to that observed with cigarette smoke, but it did not change lambda 0. However, substance P (SP) increased lambda 0, and repeated administration of SP produced a significant tachyphylaxis in animals with and without capsaicin pretreatment in a fashion similar to that noted with cigarette smoke inhalation. Acrolein decreased lambda 0 in animals with and without capsaicin. Colchicine inhibited the cigarette smoke-induced increase in lambda 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Effective site of bronchodilation by beta-adrenergic and anticholinergic agents in patients with chronic obstructive pulmonary disease: direct measurement of intrabronchial pressure with a new catheter.

To study the effective site of bronchodilators in patients with chronic obstructive pulmonary disease (COPD), a catheter tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus, 3 mm inner diameter, in 14 patients with COPD. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (RP) was obtained by the subtraction of RC from RL. This technique permitted identification of the site of changes in airway resistance. Atropine sulfate (5 mg/ml) was continuously inhaled during tidal breathing for 1 min by seven patients (Group A), and the other seven patients (Group B) inhaled fenoterol (1 mg/ml) for 1 min. The doses that were actually delivered were 0.75 mg for atropine sulfate and 0.15 mg for fenoterol. The baseline resistances of RC and RP were 3.9 +/- 0.8 and 3.7 +/- 0.6 cm H2O/L/s in Group A, and 4.3 +/- 0.5 and 3.5 +/- 0.4 cm H2O/L/s in Group B, respectively. Both atropine sulfate and fenoterol significantly decreased RL by an average of 2.4 and 2.6 cm H2O/L/s, and there was no significant difference between them (p greater than 0.20). The percentage decrease in resistance from the baseline values by fenoterol did not differ significantly between RC and RP (p greater than 0.20). However, atropine sulfate significantly decreased RC more than RP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma.

To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine.

The contractile response of isolated guinea pig trachea to histamine was potentiated in the presence of the histamine N-methyltransferase (HMT) inhibitor SKF 91488, whereas the diamine oxidase inhibitor aminoguanidine was without effect. SKF 91488 shifted in a concentration-dependent fashion the concentration-response curves to histamine to lower concentrations with the maximum by 1 log unit. The trachea contained significant HMT activity (45.4 +/- 5.0 pmol/min/mg protein). In situ hybridization to detect HMT mRNA indicated that HMT mRNA was present in the epithelium and endothelium, being more abundant in the former. Removal of the epithelium shifted the concentration-response curves to histamine to lower concentrations by 0.8 log unit, and SKF 91488 caused only a slight shift of histamine concentration-response curves in tissues denuded of epithelium. These findings suggest that HMT regulates the contractile response of guinea pig trachea to histamine, and epithelial removal-induced bronchial hyperresponsiveness to histamine is largely explained by the loss of HMT in the epithelium.

Animals↗
PubMed1991

Pre- and postjunctional muscarinic receptor subtypes in dog airways.

To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ED50) and the maximum (EDmax) contractions and the pA2 values were atropine greater than or equal to 4-DAMP methiodide greater than pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

Acetylcholine↗
PubMed1991

Effective site of bronchodilation by antiasthma drugs in subjects with asthma.

We studied the effective sites of airway response to atropine and fenoterol aerosols and to the intravenous injection of aminophylline in patients with stable and spontaneous asthma, by the simultaneous assessment of respiratory resistance (Rrs) and anatomic dead space (VD). Central airway response was determined by VD, and overall response was determined by Rrs. Peripheral airway response was inferred from Rrs when the change in VD was slight. Atropine (4 mg/ml) or fenoterol (0.4 mg/ml) was continuously inhaled during tidal breathing for 5 minutes. Inhalation of both atropine and fenoterol increased Grs (reciprocal of Rrs) (p less than 0.01) with a simultaneous increase in VD (p less than 0.01) in the patients with stable and spontaneous asthma. Fenoterol increased Grs more than did atropine at an equivalent increase in VD in patients with spontaneous asthma (p less than 0.05). Intravenous injection of aminophylline (250 mg) had no effect on either Grs or VD in patients with stable asthma, but it significantly increased Grs (p less than 0.01) without change in VD in patients with spontaneous asthma. These results suggest that the predominant sites of bronchodilation induced by inhaled atropine are the central airways, that those sites induced by intravenous injection of aminophylline are the peripheral airways, and that inhaled fenoterol dilates both the central and peripheral airways in subjects with asthma. Differences among clinically used bronchodilators on the effective sites may be considered in the treatment of bronchial asthma.

Adult↗
PubMed1991

Chemical oxidant potentiates electrically and acetylcholine-induced contraction in rat trachea: possible involvement of cholinesterase inhibition.

To determine the roles of oxidants in airway responsiveness, we studied the effects of the chemical oxidant N-chlorosuccinimide (NCS) on the contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh) in isolated rat tracheal smooth muscle segments. Effects of NCS on the contractile response to EFS (5 Hz, 20 sec of duration, 50 V) reached the maximum with a 60-min incubation time. NCS potentiated the contractile response to EFS, with a maximum effect at 3 x 10(-7) M and to ACh, with a maximum effect at 3 x 10(-6) M. Thus, at a concentration of 3 x 10(-6) M, NCS significantly decreased log ED50 concentration of ACh from a control value of -5.56 +/- 0.05 to -6.24 +/- 0.06. Physostigmine (10(-7) M), at a concentration that did not alter resting tension, mimicked NCS-induced effects on contractile responses to ACh and EFS with the greater degree of shift in the respective dose-response curves. However, NCS failed to alter dose-response curves to carbachol. Removal of the epithelium shifted the dose-response curves to ACh to lower concentrations, but NCS showed similar effects on dose-response curves to ACh with and without the epithelium. Active staining showed that both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) activities were found in the smooth muscle of the rat trachea. NCS inhibited both enzyme activities from rat tracheal homogenates in a concentration-dependent fashion. These results suggest that NCS potentiates cholinergically induced contraction by decreasing cholinesterase activity and that the oxidation of cholinesterase may cause hyperresponsiveness of airway smooth muscle by inhibition of the enzyme activity.

Acetylcholine↗
PubMed1991

A small airway pressure sensor for humans.

We developed a small airway pressure sensor for humans. This sensor catheter was introduced to the right lower lobe bronchus through a fiberoptic bronchoscope until the tip was wedged, at which point the bronchoscope was removed. We measured small airway pressure using this sensor. Simultaneously, we measured mouth flow, mouth pressure and transpulmonary pressure by the esophageal balloon technique during tidal breathing. The present method is called an anterograde method. By this method, we obtained central airway resistance and peripheral airway resistance. A significant increase in peripheral airway resistance, compared to normal subjects, has been confirmed as a symptom of chronic obstructive pulmonary disease.

Airway Resistance↗
PubMed1990

Ozone increases susceptibility to antigen inhalation in allergic dogs.

To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.

Acetylcholine↗
PubMed1990

Prolonged hypoxemia after 10 min walking exercise in aged patients with chronic obstructive pulmonary disease.

Although the behavior and factors of exercise tolerance have been studied during exercise in patients with chronic obstructive pulmonary disease (COPD), little attention has been paid to the after-effects of such activity. Arterial oxygen saturation (SaO2) was monitored during and after a 10 min walking exercise in aged patients with COPD. Neither baseline SaO2 nor mean SaO2 during exercise correlated to the 10 min walking distance. However, the recovery time of SaO2 to the baseline value shows significant correlation to the 10 min walking distance. Careful attention should be paid to prolonged hypoxemia after exercise in severe cases of COPD.

Aged↗
PubMed1989

Laryngeal resistance immediately after panting in asthmatic subjects.

The panting manoeuvre may be used during the assessment of airway resistance and in asthmatic patients during bronchial provocation testing or spontaneous asthma. To study whether panting opens the larynx in patients with asthma, laryngeal resistance was examined in six patients with stable asthma before and after methacholine induced bronchoconstriction and in another six patients with spontaneous asthma. Subjects were asked to pant and then to hold their breath immediately afterwards. Laryngeal resistance after panting was compared to that during quiet tidal breathing. Change in laryngeal resistance was estimated by a method using low frequency sound and respiratory resistance by forced oscillation at 10 Hz. Mean baseline respiratory resistance during inspiration was 0.245 and 0.470 kPa/l.s before and after methacholine in the patients with stable asthma and 0.480 kPa/l.s in the patients with spontaneous asthma. In the patients with stable asthma mean laryngeal resistance was lower after panting than during the preceding quiet tidal breathing, both before and after methacholine induced bronchoconstriction (by 0.08 before and by 0.065 kPa/l.s after). In contrast, the patients with spontaneous asthma showed an increase in laryngeal resistance after panting of 0.089 kPa/l.s. The magnitude of change in laryngeal resistance after panting was similar to the change in respiratory resistance in the patients with spontaneous asthma and in the patients with stable asthma after methacholine, but was greater than the change in respiratory resistance in the patients with stable asthma before methacholine. These results suggest that panting may cause different effects on the laryngeal aperture in patients with stable and spontaneous asthma.

Adult↗
PubMed1988

Partitioning of large and small airway resistance in human measured by an anterograde catheter with a tip micromanometer.

We measured lateral pressure in airways 3 mm in internal diameter in three normal subjects using an anterograde catheter with a tip micromanometer. The pressure was used to partition total pulmonary resistance into a large airway resistance component between the mouth and the pressure sensor and a small airway resistance component between the pressure sensor and alveoli. Large airway resistance and small airway resistance during inspiration were 2.3 +/- 0.4 and 0.9 +/- 0.2 cmH2O/liter/sec (mean +/- S.E.), respectively, and small airway resistance was 29% of the total pulmonary resistance. We suggest that the present technique may be useful for determining the localization of airway resistance in human subjects.

Adult↗