To determine the effects of electrical hypoglossal nerve and submental stimulation on upper airway collapsibility, we examined the pressure-volume (P-V) relationships during bilateral supramaximal stimulation of the distal cut hypoglossal nerve ends over a range of frequencies from zero to 100 Hz in the sealed upper airway of 10 anesthetized supine dogs. Animals were artificially ventilated with 50% O2 and maintained under relative hyperoxia and hypocapnia during the study to eliminate the ventilatory drive output. Sealed upper airway pressures were obtained during random injections of different volumes of air from zero to 50 ml with and without hypoglossal nerve stimulation, and the upper airway P-V curves were obtained. The characteristics of the P-V curves were as follows: (1) the upper airway compliance defined as the slope of the regression of P-V curves fell from 4.07 +/- 0.33 ml/cm H2O without stimulation to 3.02 +/- 0.30 ml/cm H2O with stimulation at 50 Hz and plateaued at frequencies greater than 50 Hz, and (2) the volume at a given pressure during stimulation was larger than that without stimulation. The effects of submental stimulation on upper airway collapsibility were similar to those of hypoglossal nerve stimulation. These results suggest that the increase of upper airway muscle tone by hypoglossal nerve or submental stimulation stiffens the upper airway and that increases in muscle tone expand the upper airway.

ulmonary ischemia -reperfusion injury is an important contributor to a number of pulmonary diseases, including pulmonary embolism and the acute respiratory distress syndrome, and to post-transplant complications. 1 Studies in the heart, intestines and other tissues have suggested that reperfusion-induced injury is mediated by the production of oxygen free radicals. 2,3 The same mechanism appears to be involved in the effect of ischemia-reperfusion on the pulmonary circulation, 4 but it remains unclear how oxygen free radicals are generated after a short period of occlusion of the pulmonary artery alone. Most previous studies investigating oxygen free radicals in reperfusion injury of the lungs have been performed in isolated lungs, 1,[5][6][7][8][9] or in animals with obstruction of both the airway and the pulmonary artery; that is, hilar occlusion. [10][11][12] In order to simulate clinical pulmonary artery occlusion and reperfusion, the generation of oxygen free radicals should be evaluated without obstructing either the airway or the bronchial circulation in in-vivo blood-perfused lungs. Although the lung is relatively resistant to reperfusion injury, 13 Murata et al reported that 24-h reperfusion after only 2 h of occlusion of the pulmonary artery alone induced numerous foci of hemorrhagic necrosis with disrupted alveoli and accumulation of leukocytes, and these pathological changes were significantly attenuated by superoxide dismutase (SOD). 14 Okubo et al recently reported that the continuous production of oxygen free radicals, using a chemiluminescence (CL) method in a 110-min hilar occlusion reperfusion, was significantly reduced by SOD. 10 However, alveolar hypoxia may have Japanese Circulation Journal Vol. 65, March 2001 affected the generation of oxygen free radicals 15 in their study. Accordingly, it still remains unclear how superoxide is generated in reperfusion after a short period of pulmonary artery occlusion. Because of this lack of data, the best time of onset and the duration of administration of radical scavengers, if needed, is still unclear. Thus, we investigated the time course of the generation of superoxide in reperfusion after a 2-h pulmonary artery occlusion using 2-methyl-6-[pmethoxyphenyl]-3,7-dihydroimidazo[1,2-]pyrazin-3-one (MCLA), which is a sensitive and specific CL probe for the detection of superoxide, [16][17][18] as well as the effect of administration of SOD on CL, in the in-situ rat lung. Methods Photon Counting SystemThe CL monitoring system (Fig 1) has been described previously. 18,19 Briefly, experiments were carried out in a special light-proof box with an R375 photomultiplier tube (Hamamatsu Photonics Inc, Hamamatsu, Japan), sensitive in the range of 160-850 nm, and a dry air jacket located in front of the shutter and window of the photomultiplier tube to avoid moisture condensation. We measured CL at 10 s intervals and the data were displayed as the count per 10 s. AnimalsTwenty-two male Wistar rats, weighing 350-450 g, were housed in a constant-temperature facil...

We investigated whether the ventilatory threshold (VET) could be detected in 25 patients with severe chronic obstructive pulmonary disease (COPD). Exercise on a treadmill was performed until symptom-limited maximum oxygen uptake (VO₂SL) was obtained. VET was absent in 14 patients (56%, VET(-) group) and present in the others (44%, VET(+) group). Basal pulmonary functions and dyspnea index (V_{E, SL}/MVV) were not different between the two groups. Endurance time and exercise tolerance (VO₂SL/bw) were significantly less in VET(-) than in VET(+). In the former group, Pao₂ and pH at maximal exercise decreased and Paco₂ increased significantly, but HCO₃^- did not change compared with the corresponding values before exercise. In the latter group, Paco₂ at maximal exercise increased significantly, and pH and HCO₃^- decreased significantly compared with the values before exercise, but Pao₂ did not. The changes in Pao₂ and Paco₂ were not different between the two groups, but changes in pH and HCO₃^- in VET(+) were greater than those in VET(-). These results suggest that the absence of VET in some COPD patients indicates a lower exercise capacity without producing metabolic acidosis. This may be caused by rapidly developing dyspnea.

To investigate whether increased release of acetylcholine may be involved in propranolol-induced bronchoconstriction (PIB), the inhibitory effect of pilocarpine (Pilo), an agonist of M2-muscarinic receptors that in 11 stable asthmatic subjects. The bronchial responsiveness to Pilo was also measured in terms of Dmin, defined as the cumulative dose at the point where respiratory resistance (Rrs) began to increase. In PIB, the maximum increase in Rrs (Rrs max) after stopping inhalation for 1 min was measured. Atropine reversed PIB. After pilocarpine pretreatment at a dose equal to Dmin, Rrs max divided by baseline Rrs decreased significantly from 206.6 +/- 61.1 to 163.0 +/- 42.6% (mean +/- SD) (p = 0.001). The ratio of PIB (Rrs max/baseline Rrs) with Pilo to PIB without Pilo correlated inversely according to the pretreatment dose (Dmin) of Pilo (p < 0.05). These results suggest increased release of acetylcholine in PIB and that M2-muscarinic receptors are at least in part functioning in stable asthmatic airways.

To examine the effects of sustained hypoxia on upper airway and chest wall muscle activity in humans, we measured genioglossus muscle (GG) activity, inspiratory intercostal muscle (IIM) activity, and ventilation during sustained hypoxia in 17 normal subjects and 17 patients with obstructive sleep apnea (OSA). The trial of sustained hypoxia was performed as follows: after an equilibration period of 3 min, isocapnic hypoxia (arterial O2 saturation = 80 +/- 2%) was maintained for 20 min. GG EMG was measured with a fine-wire electrode inserted percutaneously, and IIM EMG was measured with surface electrodes. Ventilatory response to sustained hypoxia was initially increased and subsequently decreased. Stable phasic GG activity during spontaneous tidal breathing was observed in 6 normal subjects and 10 patients with OSA. Responses of GG and IIM activities to sustained hypoxia showed a biphasic response qualitatively similar to the ventilatory response in these 16 subjects. The absolute value of the subsequent decline in GG activity was similar to that of the initial increase, whereas the subsequent decline in IIM activity was smaller than that of the initial increase. Percent GG activity was significantly lower than both percent IIM activity and percent minute ventilation during the decline and plateau phases. There were no significant differences in ventilatory and EMG responses between the normal subjects and the patients with OSA. We conclude that, during wakefulness, upper airway muscle activity declined to a greater extent than inspiratory pump muscle activity during sustained hypoxia.