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Biomedical subjects

C Shindoh

Publications and source records attributed to C Shindoh.

35 records · Page 2Linked to original sources

Effect of N-acetylcysteine on diaphragm fatigue.

It has recently been postulated that diaphragm fatigue may be due, at least in part, to a form of low-grade injury to subcellular organelles. Moreover, several studies have shown that thiol-containing compounds can protect cardiac and striated skeletal muscle organelles from the deleterious effects of a number of physiological stresses. The purpose of the present study was to determine whether pretreatment with N-acetylcysteine (NAC), a thiol-containing compound, would attenuate the rate of development of diaphragmatic fatigue. Studies were performed with the use of an in situ rabbit diaphragm strip preparation that permitted direct and continuous measurement of diaphragm tension development. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 30/min (20-Hz trains) for 20 min. The diaphragm force-frequency relationship (10-, 20-, 50-, and 100-Hz stimuli) was assessed immediately before and after fatigue trials and then again 20 min into the period of recovery. Half the animals were treated with intravenous NAC before fatigue, whereas the remaining animals were given intravenous saline. The rate of development of fatigue was markedly greater in saline-treated control than in NAC-treated animals, with reductions in tension of 55 +/- 3 and 34 +/- 3%, respectively, in these two groups of animals over 20 min (P less than 0.001). Although rhythmic stimulation resulted in a downward shift in the force-frequency relationship in both NAC- and saline-treated animals, the magnitude of this shift was substantially greater in saline-treated animals (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Aging effect on oxygen consumption of respiratory muscles in humans.

The first purpose of the present study was to develop a new method to examine oxygen consumption of respiratory muscles (VO2resp) in human subjects. The apparatus consists of an expandable dead space and a respirometer. When the dead space was increased at a constant rate (approximately 100 ml/min), minute ventilation (VE) and VO2resp increased gradually. Because the logarithm of VO2 was found to be approximately linearly related to VE, we characterized this relationship by the slope (logVO2/VE) and the intercept at VE = 0 (VO2met) of the semilog regression line. The second purpose of this study was to examine the relationship between VO2resp and aging. Six anthropometric and spirometric factors (age, height, weight, vital capacity, forced expiratory volume in 1 s, and body surface area) were analyzed in 37 normal subjects by simple and stepwise multiple regression analyses. We found a significant increase in logVO2/VE and a significant decrease in VO2met with age. In conclusion, 1) the present method is convenient to use, and we are able to study VO2resp over a wide range of ventilation without voluntary effort, and 2) age per se is one of the factors accounting for the observed increase in VO2resp with age.

Adult↗

Effects of electrical stimulation of the genioglossus on upper airway resistance in anesthetized dogs.

We examined the relationship between the frequency of stimulation of the genioglossus and upper airway resistance in six anesthetized dogs in the supine position. The upper airway was isolated from the lower airway by transecting the cervical trachea, and the pressure flow relationship of the upper airway was obtained by applying constant negative pressure (5, 10, and 20 cm H2O) to the proximal cut end of the trachea. Electrical stimulation of the genioglossus was performed at a constant voltage (10 to 20 V) and at various frequencies (as high as 100 Hz). Upper airway resistance (Rua) during both inspiration and expiration increased with an increase in tracheal negative pressure, and at each tracheal negative pressure Rua was significantly reduced by stimulation of the genioglossus. The effects of genioglossal muscle stimulation were nonlinearly dependent on the stimulating frequency. Below 50 Hz, Rua decreased markedly as the stimulating frequency was increased, but above 50 Hz, Rua plateaued at a minimum value. These findings suggest that at a stimulating frequency of more than 50 Hz, upper airway patency is stably maintained in anesthetized dogs.

Airway Resistance↗

Effects of airway anesthesia on ventilatory responses to graded dead spaces and CO2.

Ventilatory response to graded external dead space (0.5, 1.0, 2.0, and 2.5 liters) with hyperoxia and CO2 steady-state inhalation (3, 5, 7, and 8% CO2 in O2) was studied before and after 4% lidocaine aerosol inhalation in nine healthy males. The mean ventilatory response (delta VE/delta PETCO2, where VE is minute ventilation and PETCO2 is end-tidal PCO2) to graded dead space before airway anesthesia was 10.2 +/- 4.6 (SD) l.min-1.Torr-1, which was significantly greater than the steady-state CO2 response (1.4 +/- 0.6 l.min-1.Torr-1, P less than 0.001). Dead-space loading produced greater oscillation in airway PCO2 than did CO2 gas loading. After airway anesthesia, ventilatory response to graded dead space decreased significantly, to 2.1 +/- 0.6 l.min-1.Torr-1 (P less than 0.01) but was still greater than that to CO2. The response to CO2 did not significantly differ (1.3 +/- 0.5 l.min-1.Torr-1). Tidal volume, mean inspiratory flow, respiratory frequency, inspiratory time, and expiratory time during dead-space breathing were also depressed after airway anesthesia, particularly during large dead-space loading. On the other hand, during CO2 inhalation, these respiratory variables did not significantly differ before and after airway anesthesia. These results suggest that in conscious humans vagal airway receptors play a role in the ventilatory response to graded dead space and control of the breathing pattern during dead-space loading by detecting the oscillation in airway PCO2. These receptors do not appear to contribute to the ventilatory response to inhaled CO2.

Administration, Inhalation↗

Role of CO2 responsiveness and breathing efficiency in determining exercise capacity of patients with chronic airway obstruction.

We examined the role of CO2 responsiveness and breathing efficiency in limiting exercise capacity in 15 patients with chronic airway obstruction (FEV1 = 0.88 +/- 0.25 L, mean +/- SD). Responses of minute ventilation and P0.1 (mouth pressure 0.1 s after the onset of occluded inspiration) to hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) were measured by rebreathing, and the ratio of the two (delta VE/delta P0.1) was defined as an index of breathing efficiency during hyperventilation. Exercise capacity was measured as symptom-limited, maximal oxygen consumption (VO2max/BW) in an incremental treadmill test and also as the 12-min walking distance (TMD). All patients discontinued the treadmill test because of dyspnea, and the exercise capacity correlated with the degree of airway obstruction, although there was a wide variability among patients with comparable FEV1. There were no significant correlations between the responses to CO2 and exercise capacity. However, there was a significant correlation between delta VE/delta P0.1 and VO2max/BW (r = 0.87, p less than 0.001) or TMD (r = 0.78, p less than 0.001), and these correlations remained significant even when the relational effects of FEV1 were taken out. These results support the hypothesis that airway obstruction and breathing efficiency are important, but that CO2 responsiveness is not a major factor in determining the exercise capacity of patients with chronic airway obstruction.

Aged↗

Effect of digitalis on the diaphragm in anesthetized dogs.

We examined the effect of digitalis on diaphragmatic contractility and fatigability in 19 anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. In a first group of five dogs, Pdi-stimulus frequency relationships were compared before and after administration of ouabain in doses of 0.01, 0.02, and 0.04 mg/kg. In a second group, diaphragmatic fatigue was produced by bilateral phrenic nerve stimulation at 30 Hz. Ten seconds of stimulation and 15 s of mechanical ventilation were repeated for 30 min. The rates of decrease in Pdi were compared between two groups, one of 0.05 mg/kg deslanoside-treated dogs (n = 7) and one of nontreated dogs (n = 7). After ouabain administration Pdi was significantly greater at each frequency in a dose-dependent manner. On the other hand, the rate of decrease in Pdi in the deslanoside group was significantly smaller than that in the nontreated group, whereas deslanoside did not greatly change the Pdi-frequency curves in fresh diaphragm. We conclude that ouabain improves contractility of the fresh diaphragm and that deslanoside has a protective effect against fatigability.

Animals↗

Ventilatory response to phasic contraction and passive movement in graded anesthesia.

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.

Anesthesia, General↗

Upper airway response during bronchoprovocation and asthma attack.

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.

Adult↗

Effect of clenbuterol on peripheral airway obstruction in bronchial asthma.

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.

Adolescent↗

Effect of inspiratory flow rate on bronchomotor tone in normal and asthmatic subjects.

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.

Adult↗

Response to hypercapnia and exercise hyperpnea in graded anesthesia.

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)

Anesthesia↗

Noninvasive method for detecting laryngeal narrowing with low-frequency sound.

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.

Animals↗

Effect of local vibration on ventilatory response to hypercapnia in normal subjects.

We studied the effects of local high frequency mechanical vibration on ventilatory (VE) and occlusion pressure (P0.1) responses to CO2 rebreathing in twelve normal subjects. Three kinds of vibration procedures were employed: a) sustained vibration over the tendon of the quadriceps femoris near the knee, b) sustained vibration of the right 2nd or 3rd parasternal intercostal spaces and c) 'in-phase' chest wall vibration applied during inspiration on the right 2nd or 3rd parasternal intercostal spaces and during expiration on the right 9th or 10th intercostal spaces anterior to the midaxillary line. The slopes of VE response to hypercapnia (delta VE/delta PETCO2) were 2.05 +/- 0.26 (mean +/- SE), 2.48 +/- 0.24, 2.82 +/- 0.32 and 3.35 +/- 0.38 l.min-1/mmHg in the control state, during tendon vibration of quadriceps femoris, sustained chest wall vibration and 'in-phase' chest wall vibration, respectively. This sequential increase in slopes was significant compared to the control values. The effect of vibration on the P0.1 response to hypercapnia was similar to that of VE. We conclude that local mechanical vibration facilitates responsiveness to hypercapnia.

Adult↗