Tatsuya Chonan

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.

Effects of focal cooling of the ventral medullary surface on breathing pattern and blood pressure in dogs

We assessed the effect of focal graded cooling of the ventral medullary surface (VMS) on breathing pattern and blood pressure in 15 anesthetized, vagotomized and artificially ventilated dogs. Diaphragmatic electromyogram or phrenic neurogram, referred to as Ec, and blood pressure (BP) were obtained during localized (2 x 2 mm2) cooling of the VMS. Greatest depression of both Ec and BP was obtained by cooling in the areas located 4-9 mm caudal to the foramen cecum (Fc) and lateral to the pyramids. Mild cooling in these intermediate areas decreased both inspiratory duration (Ti) and the rate of rise of Ec (Ec/Ti), but respiratory rate was unchanged. Cooling of the rostral areas (0-3 mm from Fc) induced mild depression of Ec amplitude due to reduction in Ec/Ti without changing Ti, and prolonged expiratory duration (Te) significantly. Cooling of the caudal areas (12-18 mm from Fc) reduced Ec amplitude mildly due to reduction in Ti without affecting Ec/Ti, and shortened Te greatly. Cooling of the rostral areas produced mild fall in BP, but cooling of the caudal areas did not affect BP significantly. It is suggested that rostral and intermediate parts of the VMS participate in the shaping of inspiratory drive, whereas wide areas of the VMS including caudal part are involved in the determination of respiratory timing. It is also suggested that the rostral and intermediate parts, and not the caudal part, of the VMS are important in the regulation of vasomotor tone.

Effect of intramedullary procaine injection on tracheal tone and phrenic neurogram

To map the superficial locations which are involved in the control of respiration and tracheal smooth muscle tone in ventrolateral medulla, we examined the effects of local anesthesia on phrenic activity and tracheal tone in twelve anesthetized, paralyzed, and artificially ventilated dogs. 0.5 microliter of 5% procaine was injected 0.3 to 0.5 mm below the surface unilaterally to the ventral superficial layer (from the rostral part of the trapezoid body to the caudal hypoglossal rootlets and lateral from the pyramids to 5.5 mm from the midline), which included rostral, intermediate and caudal areas, and the area lateral to the hypoglossal rootlets. The peak amplitude of the integrated phrenic neurogram was decreased by procaine injection to the intermediate area and the area lateral to the hypoglossal rootlets. Tracheal tone decreased only by procaine injection to the intermediate area. In the intermediate area, some injections decreased either phrenic output alone or tracheal tone alone. These results suggest that the two ventral medullary areas, i.e. the intermediate and caudolateral parts, contain neural structures which are involved in the shaping of phrenic output, but only the intermediate area is involved in the regulation of tracheal tone. It is also suggested that, in the intermediate area, the structures responsible for the maintenance of respiration and tracheal tone are, at least in part, separable.

Does Sustained Hypoxia Have Biphasic Effects on the Sensation of Dyspnea

The effect of sustained hypoxia on respiration is reported to be biphasic and comprised of an initial stimulatory phase mediated by peripheral chemoreceptors and a following depressive phase caused by central mechanisms (Neubauer, 1990). However, it is not clear how sustained hypoxia affects respiratory sensations. In this study we wished to ascertain whether sustained hypoxia has a biphasic effects on the sensation of dyspnea as well as on ventilation.

Responses of upper airway muscles to gastrocnemius muscle contraction in dogs

We studied electromyographic (EMG) responses of the alae nasi (AN) and the posterior cricoarytenoid (PCA) muscles, which act as upper airway dilators, during contraction of gastrocnemius muscle in six chest-intact anesthetized dogs with spontaneous breathing and in four thoracotomized, phrenicotomized and mechanically ventilated dogs with right thoracic and left cervical vagotomy. Muscle contraction was phasically induced by electrical stimulation of the intact gastrocnemius nerve or the distal cut end of this nerve for 20-30 sec. Stimulation intensity was determined as twice the motor threshold in each dog. In chest-intact animals, phasic contraction induced by intact nerve stimulation produced initial rapid increases in upper airway muscle activity, but stimulation of the distal cut end of the nerve did not show the rapid increase in upper airway muscle activity. Furthermore, stimulation of the proximal cut end did not produce any transient response with the stimulation intensity used in this study. In chest-open and vagotomized animals with artificial ventilation, responses of the upper airway muscles to contraction during the intact nerve stimulation were observed. These results suggest that the contraction of the gastrocnemius muscle activates upper airway dilating muscles via reflex mechanisms.

Effects of Changes in Breathing Pattern on the Sensation of Dyspnea during Inspiratory Loaded Breathing

The ventilatory responses to external resistive and elastic loadings of the respiratory system have been extensively studied in a variety of experimental animals as well as also humans. It has been known that there are marked differences in the pattern of breathing during sustained inspiratory loadings between awake and anesthetized subjects (Margaria et al., 1973; Cherniack and Altose,1981; Milic-Emili and Zin,1986). In awake subjects sustained external elastic loading generally leads to increased breathing frequency and decreased tidal volume, whereas inspiratory resistive loading causes decreased frequency and increased tidal volume. By contrast in anesthetized subjects the changes in respiratory frequency are small or absent and independent of the type of external loading (Milic-Emili and Zin, 1986). Because the different responses between the awake and anesthetized subjects cannot be explained as a simple reflex (Cherniack and Altose,1981; Milic-Emili and Zin, 1986), it is assumed that conscious awareness of breathing or behavioral response may be responsible for the different breathing pattern observed during inspiratory resistive and elastic loadings. However, the nature of the behavioral control has not yet been evaluated. Thus, the aim of the present study was to examine the hypothesis that the breathing pattern during inspiratory loading might be optimized through cortical response so that the sensation of dyspnea would be minimized.

Serial Submental Stimulation during Sleep in Patients with Obstructive Sleep Apnea

We previously reported that submental electrical stimulation may be an effective treatment for obstructive sleep apnea (Miki et al., 1989a, Hida et al., 1991). The mechanism of relief of apneic episodes during submental stimulation may be the contraction of genioglossus and/or geniohyoid muscles, which would open the upper airway by pulling the tongue forward (Miki et al, 1989b, Gottfried et al., 1983). However, the effects of submental stimulation during consecutive nights on apneic episodes in patients with obstructive sleep apnea (OSA) have not been studied. In the present study in order to assess whether submental stimulation is necessary for treatment every night, we examined the effects of submental stimulation for a serial four or five sleep nights on apneic episodes and changes in apneic episodes on stimulation-off nights after the stimulation nights using a portable submental stimulator which we have developed.