Biomedical subjects
Publications and source records attributed to W Hida.
The isolated upper airway pressure and flow changes during electrical stimulation of the genioglossus muscle in spontaneously breathing anesthetized dogs were measured at given pressures in the inspiratory direction. Upper airway resistance was maximal during no stimulation and decreased rapidly with stimulation at frequencies up to about 40 Hz.
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The ventilatory response to electrically induced contraction (EIC) and passive movement (PM) of hindlimb muscles at different levels of anesthesia was studied in 11 chloralose-urethan anesthetized dogs with and without rhizotomy. The level of anesthesia was assessed by corneal reflexes and measurements of the ventilatory response to hypercapnia. Muscle contraction was induced by electrically stimulating the peripheral cut ends of the sciatic and femoral nerves for 4-5 min, and PM was induced manually at the same frequency and amplitude as during EIC. In spinal intact dogs (n = 7), initial rapid increases in minute ventilation (VE) during EIC and PM were found in both light and deep anesthesia. Further increases in VE above the initial rise were seen during EIC but not PM. The initial rapid increases in VE did not differ between the two anesthetic levels. The steady-state ventilatory response during EIC decreased as anesthesia deepened but did not do so during PM. Rhizotomy (n = 4) abolished the initial rapid increase in VE during EIC and PM and the steady-state VE response to PM at both anesthetic levels. These results suggest that the transitional ventilatory response is neurally mediated from the muscles and not affected by the level of general anesthesia. Additionally, the anesthesia-induced reduction of ventilatory response may be due to depression of responsiveness to CO2 rather than to the inspiratory motoneuron pathway.
We developed a new method of direct-writing recording of the frequency dependence of dynamic compliance analysed from one cycle of breathing and pulmonary resistance. Both pulmonary resistance (RL) and frequency dependence of dynamic compliance (Cdyn.f) are calculated by Fourier-series analysis of flow and transpulmonary pressure in a single cycle of breathing. RL was obtained from fundamental harmonics. Cdyn.f was calculated from 1st and 2nd harmonics and estimated by the ratio of Cdyn at 0.5 Hz to Cdyn at zero frequency, C0.5/C0. We used fenoterol aerosol which contained 0.2 mg of fenoterol with one puff of aerosol. Two puffs of fenoterol aerosol were used in each subject and followed changes of RL, C0 and C0.5 as long as 30 min. After fenoterol inhalation RL decreased considerably and C0.5/C0 cont [C0.5/(control C0)] increased. With time, while RL was kept stable, C0.5/C0 cont increased further. We suggest that fenoterol has a potent effect on the small airways which is enhanced with time.
To investigate the mechanisms involved in increasing bronchial reactivity, we made a model of airway reactivity increase in dogs after Type C influenza virus infection. Five beagle dogs were inoculated intranasally with the virus, and the time courses of changes in the hemagglutination inhibition (HI) antibody titer and the bronchial reactivity were determined. To assess bronchial reactivity the dogs were anesthetized, and dose-response curves of pulmonary resistance were obtained against increasing concentrations of acetylcholine aerosol. The dogs infected with the virus showed mild symptoms of rhinorrhea and cough. The HI antibody titer was significantly increased in all dogs, with peak values at 1 to 3 wk after infection. The bronchial reactivity to acetylcholine began to increase towards Day 3, reached a peak at 1 to 2 wk, and returned to a normal level at 4 wk. The airway reactivity to acetylcholine at 2 wk after infection was increased by 2.3 to 6.5 times the normal value in terms of the acetylcholine provocative concentration. The mean increase was significant at 1 wk (p less than 0.05), 2 wk (p less than 0.01), and 3 wk (p less than 0.05). Although both the HI antibody titer and the airway responsiveness increased together towards 1 to 2 wk, no close relationship between these factors was observed thereafter. The present dog model of airway hyperreactivity may be useful for further investigation of the mechanism governing increase in bronchial reactivity with respiratory viral infection in normal subjects as well as in patients with asthma.
The inhibitory effect of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine (KC-404) on aerosolized methacholine- and histamine-induced increase in total respiratory resistance (Rrs) was determined in monkeys using the forced 3 Hz oscillation method and was compared with the effect of aminophylline. The effects of several derivatives of KC-404 on methacholine-induced bronchoconstriction were also determined. All of the i.v. administered pyrazolopyridine derivatives showed an inhibition of the increase in Rrs induced by aerosolized methacholine. Among these derivatives, KC-404 exerted the most potent bronchodilating effect. KC-404 also inhibited the histamine-induced increase in Rrs. These effects of KC-404 were more potent than those of aminophylline. On the other hand, the dose of KC-404 tested caused an increase in heart rate, although the degree was moderate as compared with aminophylline. From the results obtained in this study, it is considered that the pyrazolopyridine derivatives, particularly KC-404, may be promising bronchodilators for the treatment of bronchial asthma.
The mechanisms governing increased central (Rc) and peripheral airway resistance (Rp) during hemodynamic edema formation were studied in anesthetized dogs. Rc and Rp were measured by forced oscillation at 1 Hz by use of a retrograde catheter to partition resistance and a pleural capsule to detect alveolar pressure. After elevation of left atrial pressure to 30 cmH2O by inflation of the left atrial balloon, Rc gradually increased an average of 60% above control in approximately 100 min. Vagotomy had a small influence on the change. On the other hand, Rp with vagus nerves intact increased triphasically: first, it increased transiently by 160% above the control value within 15-20 min before returning to near base line. It then increased gradually for approximately 40 min and finally rose sharply up to five times the control value after approximately 100 min. With vagi cut, the initial phase disappeared, but the second gradual and final rapid phases were not affected. Several sequential mechanisms of increased Rp can be proposed: 1) transient bronchoconstriction mediated by vagal reflex; 2) gradual formation of peribronchial edema; and 3) a sharp increase in airway fluid and formation of bronchial froth. In addition, narrowing of the airways by vascular engorgement may have contributed to the increase of Rp throughout all stages.
We performed pulmonary function tests after antigen inhalation challenge in 6 patients with hypersensitive pneumonia. 2 patients showed a reduction in maximal expiratory flow at 25% vital capacity (V25) within the first 1-3 h (early reaction) followed by a decrease in vital capacity, forced expiratory volume at 1 s and increased respiratory resistance in the next 4-7 h (late reaction). In the other 4 patients, only V25 decreased within the first 1-3 h. Diffusion capacity did not change significantly. It is suggested that the small airway is the most sensitive site of reaction to an antigen inhalation challenge in hypersensitive pneumonia and that the obstructive change of the small airway could occur as the early reaction.
Bronchomotor tone after deep inspiration and bronchial responsiveness to methacholine were studied at 4:00 A.M. and 4:00 P.M. in 14 normal and 13 asthmatic subjects. Bronchomotor tone was assessed with respiratory resistance (Rrs) measured by the forced oscillation method. Bronchial responsiveness to methacholine and baseline Rrs were higher at 4:00 A.M. than at 4:00 P.M. in both normal and asthmatic subjects (p less than 0.01). The difference in methacholine threshold between 4:00 P.M. and 4:00 A.M. In asthmatics was similar to that in normal subjects. Immediately after deep inspiration, Rrs decreased more at 4:00 A.M. than at 4:00 P.M. In normal subjects. In contrast, asthmatic subjects showed a significantly greater immediate increase in Rrs after deep inspiration at 4:00 A.M. than at 4:00 P.M. It is suggested that the bronchoconstrictive effect after deep inspiration is a distinguishing characteristic of asthmatics.
We measured laryngeal resistance (Rla), upper airway resistance (Ruaw), and lower respiratory resistance below the larynx (Rlrs) during methacholine and histamine provocation in 10 normal and 12 asthmatic subjects. In another 10 asthmatic subjects, Rla was measured during medication for spontaneous asthma attack. The Rla was measured with the low-frequency sound method (see reference 9). Direct measurements of Ruaw and Rlrs were obtained using the 3-Hz forced oscillation technique with a needle inserted below the cricoid cartilage. In normal subjects, Ruaw increased in proportion to the increase in Rlrs during methacholine and histamine provocation. In asthmatic subjects, control Ruaw was higher than the control Ruaw in normal subjects (p less than 0.001) and Ruaw did not change despite an increase in Rlrs during methacholine and histamine provocation. After medication for spontaneous asthma attack, Rla decreased in proportion to the decrease in total respiratory resistance (Rrs). We conclude that in asthmatic subjects, Rla contributes to an increase in Rrs during both the nonspasmodic period and the spontaneous asthma attack but does not do so during bronchoprovocation, probably because the larynx is less sensitive than the lower respiratory tract.
A study was carried out in 6 patients with bronchial asthma to investigate the effects of clenbuterol, a beta 2-sympathomimetic bronchodilator, on peripheral airway obstruction. The basal lung functions of the patients were almost within normal range in both vital capacity (VC) and forced expiratory volume in 1 second (FEV1), but their maximal flow rates were lower in effort-independent phase of both maximal expiratory flow volume (MEFV) curve and partial expiratory flow volume (PEFV) curve. Furthermore, they demonstrated marked basal frequency dependence of dynamic compliance [CL,dyn]. Oral administration of clenbuterol (40 micrograms) produced a significant increase in the maximal flow in effort-independent phase of both MEFV and PEFV curves, and markedly decreased frequency dependence of CL,dyn in comparison with the baseline values, while it improved both VC and FEV1 to a lesser extent. These results suggest that clenbuterol preferentially reduced the peripheral airway obstruction in bronchial asthma.
In order to elucidate the mechanism of the bronchial response of monkeys to constrictive stimuli, the effects of pretreatment with aerosolized lidocaine, atropine, and isoproterenol were studied. Treatment with aerosolized lidocaine and atropine not only extinguished the cough reflex, but also decreased bronchial susceptibility to aerosolized methacholine. Moreover, the pretreatment with lidocaine blocked the histamine challenge, but atropine did not. The aerosolized lidocaine decreased the bronchoconstriction induced with methacholine, but not with histamine. Pretreatment with over 1% of isoproterenol did not extinguish the cough reflex. However, this dose of isoproterenol did suppress an increase in Rrs due to the challenge of both methacholine and histamine. Isoproterenol also decreased the bronchoconstriction due to the previous challenge by both methacholine and histamine. The antagonistic effects of lidocaine, atropine, and isoproterenol on the broncho-constriction of monkeys are discussed in relation to the subepithelial receptor.
The effect of the inspiratory flow rate during deep inspiration on the regulation of bronchomotor tone was studied in nine normal and 22 asthmatic subjects. Changes in bronchial tone were assessed by respiratory resistance measured by an oscillation method. In normal subjects with bronchoconstriction induced by methacholine a rapid deep inspiration reduced respiratory resistance more than a slow deep inspiration. Asthmatic subjects with spontaneous airway narrowing showed an increase in respiratory resistance after deep inspiration that was greater after rapid than after slow deep inspiration. On the other hand, in asthmatics with methacholine induced bronchoconstriction, bronchodilatation occurred after deep inspiration and this was also greater after rapid than after slow deep inspiration. Lignocaine inhalation attenuated both bronchoconstriction and bronchodilatation induced by both slow and rapid deep inspiration. These results suggest that the effects of deep inspiration are mediated at least in part via receptors in the airways. It is suggested that in asthmatic patients with spontaneous bronchoconstriction irritant receptor activity will be increased in proportion to the speed of inspiration. After methacholine induced bronchoconstriction stretch receptor activity is likely to behave in a similar fashion, leading to an opposite effect.
Trapped gas volume (Vtg) was obtained after 5 and 10 repeated inflation-deflation cycles between transpulmonary pressure (Ptp) = 0 and 30 cmH2O in 12 experimental groups of freshly excised rabbit lungs. Gas flow rate was 1.0 ml/s except in one group (0.4 ml/s). In lungs degassed by O2 absorption (Dabs), Vtg increased from an initial 12-15% total lung capacity (TLC) (1st cycle) to 40% TLC (10th cycle), whereas in vacuum-degassed lungs (Dvac) the final Vtg was almost unchanged, remaining at less than 20% TLC. However, with the slower flow rate, Vtg in Dvac became 60% TLC. Increased lung water was not found in Dabs and therefore could not account for the above difference. In lungs not degassed after excision, Vtg increased roughly in proportion to the duration of passive collapse at Ptp = 0. However, a single brief exposure to a negative airway pressure (Pao = -10 cmH2O) resulted in a greater rate of increase of Vtg than 15-min collapse. When any of the foregoing groups were vacuum degassed after 5 cycles, they then resembled the Dvac group and showed almost no increase of Vtg in successive cycles. In Dvac, negative Pao and 15-min collapse had only minor effects on increasing Vtg. Thus, at a flow rate of 1 ml/s vacuum degassing almost eliminated all tendencies to trap gas in rabbit lungs, but the tendency was more than restored at slower flows. Brief airway closure by negative tracheal pressure can markedly enhance subsequent trapping of collapsed lungs. Differences arising from degassing methods might be due to effects on bronchomotor tone or on the physical characteristics of airway lining.
Peribronchoarterial interstitial fluid pressure [Px(f)] was measured by wicks inserted between bronchus and artery of dog lobes filled with air, saline, 6% dextran in saline, or mineral oil. Five inflations were made to total lung capacity, with one min stops at eight selected volume levels in each cycle. Deflation recoil (measured as transpulmonary pressure, Ptp) was largest for air and least for saline and dextran, and it fell between these extremes for mineral oil. Correspondingly, Px(f) was most negative for air, slightly less negative for mineral oil, and least for saline and dextran. On the first cycle, the Px(f) for saline and dextran were nearly equal, but in later cycles Px(f) with saline drifted fairly rapidly toward alveolar pressure. By plotting Px(f) vs. Ptp, all first-cycle curves were brought toward a single line. During later cycles, Ptp and Px(f) always changed together along this line, except for saline. We conclude that 1) at fixed vascular pressure, Px(f) depends mainly on Ptp and less on lung volume; 2) large changes in Px(f) with saline suggest that at least some fluid can enter this interstitial space quite rapidly; and 3) peripheral tissue swelling with saline causes some reduction in Ptp, and both swelling and lower recoil contribute to increased trapping of saline.
We examined the relationship between response to hypercapnia and ventilatory response to exercise under graded anesthesia in eight dogs. The response to hypercapnia was measured by the CO2 rebreathing method under three grades of chloralose-urethan anesthesia. The degrees of response to hypercapnia (delta VE/delta PETCO2, 1 X min-1 X Torr-1) in light (L), moderate (M), and deep (D) anesthesia were 0.40 +/- 0.05 (mean +/- SE), 0.24 +/- 0.03, and 0.10 +/- 0.02, respectively, and were significantly different from each other. Under each grade of anesthesia, exercise was performed by electrically stimulating the bilateral femoral and sciatic nerves for 4 min. The time to reach 63% of full response of the increase in ventilation (tauVE) after beginning of exercise was 28.3 +/- 1.5, 38.1 +/- 5.2, and 56.0 +/- 6.1 s in L, M, and D, respectively. During steady-state exercise, minute ventilation (VE) in L, M, and D significantly increased to 6.17 +/- 0.39, 5.14 +/- 0.30, and 3.41 +/- 0.16 1 X min-1, from resting values of 3.93 +/- 0.34, 2.97 +/- 0.17, and 1.69 +/- 0.14 1 X min-1, respectively, while end-tidal CO2 tension (PETCO2) in L decreased significantly to 34.8 +/- 0.9 from 35.7 +/- 0.9, did not change in M (38.9 +/- 1.1 from 38.9 +/- 0.8), and increased significantly in D to 47.3 +/- 1.9 from 45.1 +/- 1.7 Torr.(ABSTRACT TRUNCATED AT 250 WORDS)
We measured laryngeal narrowing with low-frequency sound in human subjects. A low-frequency sound of 800 Hz was forced into the mouth, and sound-pressure amplitude above (SPAa) and below the vocal cord (SPAb) was detected using two separate microphones at the anterior neck. If the subject voluntarily narrowed the larynx at functional residual capacity, the increased respiratory resistance (Rrs) was only caused by increased laryngeal resistance, and SPAa was increased and SPAb was decreased. The percent changes of SPAa (SPAa%) minus that SPAb (SPAb%) from the initial values (SPAa% - SPAb% = Y) was proportional to the increase of Rrs from the initial control state (X, cmH2O X 1-1 X s); Y = 22.4 X1.20 (coef of correlation, r = 0.96, P less than 0.01). We confirmed similar proportions in dogs by manually narrowing the vocal cord. When laryngeal resistance was directly measured by tracheal puncture with a needle, the proportions between Y and X were not significantly dependent on the increase of Rrs below the vocal cord induced by methacholine inhalation in human subjects and histamine injection in dogs. We concluded that the increase of laryngeal resistance from the initial state could be detected noninvasively by using low-frequency sound.