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Biomedical subjects

C Shindoh

Publications and source records attributed to C Shindoh.

At least 19 recordsLinked to original sources
PubMed1992

Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.

Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline-treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Bronchial asthma].

In the first study, to clarify whether increased vagal afferent activity contributes to the increase in ventilatory response to CO2 in patients with asthma, we examined the effects of prostaglandin E2 (PGE2) inhalation on the respiratory response to CO2 in seven normal subjects. After PGE2 inhalation, the ventilatory and occlusion pressure responses to CO2 increased significantly compared with those after saline inhalation, with no increase in respiratory resistance. These results suggest that increase in vagal afferent activity may play a role in the increased hypercapnic response during acute exacerbations of asthma. In the second study, to clarify the reduced respiratory chemosensitivity associated with asthma-related deaths, we examined the hypercapnic and hypoxic ventilatory responses in five patients with near-fatal asthma who were given artificial ventilation and/or became unconsciousness during an acute exacerbation of asthma. Hypoxic ventilatory response was significantly lower in these subjects than in patients with uncomplicated asthma and normal subjects, suggesting that lowered hypoxic ventilatory response may be related to death from asthma.

Asthma↗
PubMed1991

Decrease in functional residual capacity during inspiratory loading and the sensation of dyspnea.

The purposes of the present study were to determine the changes in functional residual capacity (FRC) during inspiratory loading and to examine their mechanisms. We studied seven normal subjects seated in a body plethysmograph. In both graded inspiratory elastic (35, 48, and 68 cmH2O/l) and resistive (21, 86, and 192 cmH2O.l-1.s) loading, FRC invariably decreased from control FRC and phasic expiratory activity increased. The reduction in FRC was greater with greater loads. A single inspiratory effort against an inspiratory occlusion at three different target mouth pressures (-25, -50, and -75 cmH2O) and durations (1, 2, and 5 s) also resulted in a decrease in FRC with an increase in expiratory electromyogram activity in the following expiration. The decrease in FRC was greater with greater target pressure and duration. This decrease in FRC is qualitatively similar to that during inspiratory loaded breathing, and we suspect that the same mechanisms are at work. Because neither vagal nor chemoreceptor reflex can account for these responses, we suspect conscious awareness of breathing or behavioral control to be responsible. In an additional study, the sensation of discomfort of breathing during elastic loading decreased with a decrease in FRC. These results suggest that the reduced FRC may be due to behavioral control of breathing to reduce the sensation of dyspnea during inspiratory loading.

Adult↗
PubMed1991

Effect of acute fasting on diaphragm strength and endurance.

The effects of short periods of fasting on diaphragm contractile function remain unclear. The purpose of the present study was (1) to examine the relationship between duration of acute fasting and diaphragm contractile performance, and (2) to assess the effects of fasting on diaphragm glycogen stores and the relationship between changes in diaphragm function and alterations in muscle glycogen stores. Studies were performed on four groups of Syrian hamsters (nine animals in each group). One group served as a control and was allowed to feed normally, whereas the other three groups were fasted for either 1, 2, or 3 days. Diaphragm strips from animals were studied in vitro by measuring tension during electrically induced contractions. Two strips from each animal were studied; one strip was examined with a bath glucose equal to the prevailing blood glucose, and the second was preincubated in a high glucose solution (170 mg/dl) for 20 min. Fasting resulted in reductions in body weight, blood glucose concentrations, diaphragm strength, and diaphragm endurance in strips tested at the prevailing blood glucose levels. These effects were pronounced in animals fasted for 3 days, with little or no change in diaphragm contractility observed in animals fasted for shorter periods. Diaphragm weight, thickness, and glycogen content were unchanged in the fasted animals, as was the weight of the soleus muscle. Preincubation of strips from 3-day-fasted animals in a high glucose medium resulted in a significant increase in diaphragm strip strength and endurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of elastic loading and exercise on pulmonary gas exchange in dogs.

We assessed the effects of negative intrathoracic pressure induced by inspiratory elastic loading on pulmonary, gas exchange with and without electrically induced hindlimb exercise in 8 normal, anesthetized dogs. Two elastic loads (EL) were used; one of 81 and one of 140 cmH2O/liter. These are equivalent to doubling and tripling the normal elastance of the dog's respiratory system, respectively. Elastic loading decreased ventilation and caused hypoxemia and hypercapnia, but it did not affect systemic arterial pressure or heart rate. During exercise, increase in ventilation was limited, whereas increase in cardiac output was not affected by elastic loading. Alveolar-arterial O2 tension difference (A-aDO2) was not changed significantly by exercise alone. However, elastic loading accompanied by exercise increased A-aDO2. Although comparable end-inspiratory pleural pressure was achieved with large EL (-29 +/- 2 cmH2O, mean +/- SE) and small EL with exercise (-30 +/- 2 cmH2O), the latter increased A-aDO2 whereas the former did not. Large negative intrapleural pressure combined with increased cardiac output may have caused transient interstitial edema.

Animals↗
PubMed1991

[Restrictive lung disease].

It was found that functional residual capacity (FRC) invariably decreased during inspiratory elastic loaded breathing and that its magnitude increased progressively with an increase in the intensity of the load. This response could not be explained by chemoreflexes nor neural reflexes. Because the sensation of dyspnea decreased at lowered FRC (FRC-0.5 liter) than that at FRC during elastic loading, we speculate that FRC decreased behaviorally during elastic loading to reduce the sensation of dyspnea. We found that the respiratory muscle became fatigued more easily at FRC than at lowered FRC during elastic loading. We therefore conclude that the decrease in FRC may be one of the compensatory mechanisms during elastic loaded breathing.

Functional Residual Capacity↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗