Ventilatory effects of doxapram in conscious human subjects

The ventilatory effects of a bolus intravenous dose of doxapram (0.37 to 0.47 mg/kg) were studied in ten healthy normal subjects. An immediate significant (p less than 0.001) increase in minute ventilation (VE) was due, in equal part, to significant increases in tidal volume (VT) and frequency (f). The inspiratory (TI) and expiratory time (TE) per breath decreased significantly. Mouth occlusion pressure increased significantly, in association with the increase in VT; there was no change in the ratio of VE to mouth occlusion pressure, indicating that respiratory mechanics did not alter. These results indicate that doxapram increases ventilation in conscious, normal man by an increase in inspiratory neuromuscular drive and a change in central breath timing. The ventilatory and mouth occlusion pressure responses to progressive isocapnic hypoxia and progressive hyperoxic hypercapnia were significantly altered by an intravenous infusion of doxapram (1 mg/min) only in the elevations (Y-intercepts) of the slopes of VE and mouth occlusion pressure; the regression coefficients did not change significantly. These results indicate that in conscious normal subjects, doxapram acts on both the peripheral and central respiratory receptors.     

Effects of exercise modality on patterns of ventilation and respiratory timing.

Ventilatory patterns and respiratory timing were measured in 14 subjects during cycling (CYC) and treadmill exercise (TM) at similar leg frequencies (fLEG) to determine if mode of exercise affects patterns of ventilation and respiratory timing. Measurements of breathing frequency (fR), tidal volume (VT), expired ventilation (VE), and inspiratory (TI) and expiratory (TE) time were obtained at fLEG of 50, 70, and 90 rev.min-1 (rpm) for CYC and at similar incremental fLEG (strides.min-1; spm) during TM achieved by increasing belt speed at 0% grade. CYC exercise intensity was approximately 50% VO2,max at all fLEG, whereas VO2 increased progressively with TM. fR increased significantly (P < 0.001) with increasing fLEG of TM (20.5 +/- 4.6, 25.4 +/- 5.8, and 36.3 +/- 7.6 breaths.min-1; mean +/- SD), but during CYC fR changed significantly (P < 0.05) only between fLEG of 70 and 90 rpm (25.0 +/- 5.9 vs 28.5 +/- 6.9 breaths.min-1). Both average breath TI and TE obtained by grouping into incremental ranges of fR decreased significantly (P < 0.05) with increasing fR up to 36 breaths.min-1 and the relationships of TI and TE to fR, TI to TE, and central inspiratory drive (VT/TI) to VE were the same for CYC and TM. Group average fR and fLEG were synchronized during TM, but individual subjects did not exhibit a high degree of entrainment. This study shows respiratory timing patterns to be independent of mode of exercise over the range of fR observed when describing patterns by grouping into incremental ranges of fR.     

Neuromechanical properties in obese patients during carbon dioxide rebreathing

During hypercapnia-induced hyperventilation, obese patients with a prior history of alveolar hypoventilation appear to have significantly more blunted ventilatory response than simply obese patients who never retained carbon dioxide. In addition, these patients with former obesity-hypoventilation syndrome have decreased neuromuscular responses as measured by way of the mouth occlusion technique when compared with either the patients with simple obesity or normal subjects. The patients with simple obesity appear to have augmented responses in comparison with normal subjects. Simple mechanical considerations and baseline breathing variables failed to distinguish the simple obesity group from the group with former obesity-hypoventilation syndrome. Thus, the decreased neuromuscular responsiveness to carbon dioxide (mouth-occlusion pressure/end-tidal carbon dioxide pressure) among the group with former obesity-hypoventilation syndrome when compared with that in the group with simple obesity is a consequence of a blunted neural (central) drive, and not due to any apparent worse mechanical limitations. The augmented mouth-occlusion pressure/end-tidal carbon dioxide pressure and increased integrated, rectified electromyographic signal of the diaphragm found in the group with simple obesity presumably reflect their attempt to maintain ventilatory homeostasis in the presence of severe respiratory loads. Neuromechanical coupling values, as reflected in the integrated electromyographic signal of the diaphragm versus transdiaphragmatic pressure and mouth-occlusion pressure versus mean inspiratory flow, are identical in the two groups. On the basis of these studies, it would appear that although mechanical loads put all obese patients at a disadvantage, the addition of an acute extra load on the respiratory system produces the obesity-hypoventilation syndrome in those obese persons who have truly blunted central hypercapnic responses.     

The pattern and timing of breathing during incremental exercise: a normative study.

Clinical evaluation of the pattern and timing of breathing during submaximal exercise can be valuable for the identification of the mechanical ventilatory consequences of different disease processes and for assessing the efficacy of certain interventions. Sedentary individuals (60 male/60 female, aged 20-80 yrs) were randomly selected from >8,000 subjects and submitted to ramp incremental cycle ergometry. Tidal volume (VT)/resting inspiratory capacity, respiratory frequency, total respiratory time (Ttot), inspiratory time (TI), expiratory time (TE), duty cycle (TI/Ttot) and mean inspiratory flow (VT/TI) were analysed at selected submaximal ventilatory intensities. Senescence and female sex were associated with a more tachypnoeic breathing pattern during isoventilation. The decline in Ttot was proportional to the TI and TE reductions, i.e. TI/Ttot was remarkably constant across age strata, independent of sex. The pattern, but not timing, of breathing was also influenced by weight and height; a set of demographically and anthropometrically based prediction equations are therefore presented. These data provide a frame of reference for assessing the normality of some clinically useful indices of the pattern and timing of breathing during incremental cycle ergometry in sedentary males and females aged 20-80 yrs.     

Steady-state response of conscious man to small expiratory resistive loads

To determine the predominant steady-state ventilatory responses to mild expiratory flow-resistive loads, we subjected 14 normal subjects to expiratory resistances of 0-10 cm H2O/L/sec (R0-R3). Breathing patterns and abdominal muscle activity (EMG) were recorded during quiet breathing, and when ventilation was augmented by dead space breathing (7 subjects) or treadmill walking (7 subjects). Expiratory loading increased expiratory time (TE), tidal volume and mean inspiratory flow rate, while decreasing inspiratory duty cycle and respiratory frequency. Minute ventilation (VI) remained constant. These load responses were most prominent during quiet breathing, and were attenuated or abolished as VI increased. Abdominal EMG was negligible during quiet breathing, increased when VI increased, but showed no consistent response to R1-R3. Thus, the principal defense against mild expiratory loads is prolongation of expiration, accompanied by enhanced inspiratory drive. Abdominal muscle expiratory activity is elicited by increasing ventilation, but occurs only sporadically with expiratory loading of the magnitude studied.     

Chemoreflex drive and the dynamics of ventilation and gas exchange during exercise at hypoxia

We tested the hypothesis that the promotion of hypoxic ventilatory responsiveness (HVR) and/or hypercapnic ventilatory responsiveness (HCVR) mostly acting on the carotid body with a changing work rate can be attributed to faster hypoxic ventilatory dynamics at the onset of exercise. Eleven subjects performed a cycling exercise with two repetitions of 6 minutes while breathing at FIO(2) = 12%. The tests began with unloaded pedaling, followed by three constant work rates of 40%, 60%, and 80% of the subject's ventilatory threshold at hypoxia. Reference data were obtained at the 80% ventilatory threshold work rate during normoxia. Using three inhaled 100% O(2) breath tests, a comparison of hypoxia and normoxia revealed an augmentation of HVR in hypoxia, which then significantly increased proportionally with the increase in work rate. In contrast, HCVR using three inhaled 10% CO(2) breath tests was unaffected by the difference in work rate at hypoxia but did exceed its level at normoxia. The decrease in the half-time of hypoxic ventilation became significant with an increase in work rates and was significantly lower than at normoxia. Using a multiregression equation, HVR was found to account for 63% of the variance of hypoxic ventilatory dynamics at the onset of exercise and HCVR for 9%. O(2) uptake on-kinetics and off-kinetics under hypoxic conditions were significantly slower than under normoxic conditions, whereas they were not altered by the changing work rates at hypoxia. These results suggest that the faster hypoxic ventilatory dynamics at the onset of exercise can be mostly attributed to the augmentation of HVR with an increase in work rates rather than to HCVR. Otherwise, O(2) uptake dynamics are affected by the lower O(2), not by the changing work rates under hypoxic conditions.     

The effect of the phase relationship between the arterial blood gas oscillations and central neural respiratory activity on phrenic motoneurone output in cats

The aim of the present experiments in artificially ventilated, anesthetized cats was to investigate in which circumstances the timing of the arterial blood gas oscillations within the respiratory cycle can be of importance in determining phrenic motoneurone output. The phase relationship phi was defined as the relative position of the peak of the phrenic bursts within the current continuously measured PaO2 oscillations. It was judged breath by breath whether there was a relationship between phi and neural tidal volume, and neural inspiratory and expiratory duration. Within cats, PETCO2 was kept constant at about 1.5-2% above apneic threshold. It was found that phi indeed partly determined these ventilatory parameters provided the oscillations were large enough. This was evident in normoxia; in moderate hypoxia the influence of phi was demonstrable more easily, i.e. at smaller oscillation amplitudes. In both conditions the effect of phi on neural tidal volume was most pronounced. Neural tidal volume was maximal when peak inspiration coincided with the expiratory trough of the PaO2 oscillations. A 1:1 phase lock between phrenic activity and the ventilatory only occurred when the pump frequency was close to the cats own breathing frequency. Bilateral carotid sinus nerve section abolished the effects of phi.     

Abnormal ventilatory responses to hypoxia in Type 2 diabetes.

AIMS: The incidence of Type 2 diabetes is increasing, along with its associated micro- and macrovascular disease manifestations. Previous studies indicate that patients with Type 2 diabetes exhibit abnormal cardiopulmonary reflex responses to various stimuli, although the impact of hypoxia, a common physiological stimulus, on ventilatory responses has not previously been studied in humans with Type 2 diabetes. METHODS: Minute ventilation (V(E)) breathing pattern responses (total breath time, T(TOT); expiratory time, T(E); inspiratory time, T(I); inspiratory duty cycle, T(I)/T(TOT)) were measured during 5 min each of normoxia and isocapnic hypoxia (arterial O2 saturation approximately 85%) in eight subjects with Type 2 diabetes and seven age- and body mass index-matched healthy subjects. RESULTS: During normoxia, V(E) was similar in control and diabetic subjects (6.4+/-1.2, 6.4+/-1.1 l/min, respectively). In response to hypoxia, V(E) significantly increased in both groups (to 17.0+/-5.0 and 9.5+/-2.0 l/min, respectively, P<0.05), but the magnitude of increase in V(E) was significantly less in diabetic than in control subjects (P<0.05). In addition, the breathing pattern response to hypoxia differed between groups in terms of T(I)/T(TOT) and T(TOT) (P<0.05), with control subjects significantly decreasing T(TOT) and T(E) (P<0.05) while diabetic subjects tended to increase both. CONCLUSIONS: Relative to matched control subjects, Type 2 diabetic subjects exhibit blunted V(E) responses to acute isocapnic hypoxia, suggesting that this group of diabetic subjects possesses a chemoreflex ill-equipped to respond homeostatically to hypoxic challenge.     

Hypoxic respiratory response during acute stable hypocapnia

The hypoxic ventilatory response during hypocapnia has been studied with divergent results. We used volume-cycled ventilation in spontaneously breathing normal subjects to study their hypoxic ventilatory response under conditions of stable hypocapnia. Subjects were studied at three different levels of end-tidal (partial) carbon dioxide pressure (PETCO2), eucapnia and 6 and 12 mm Hg below eucapnia (mild and moderate hypocapnia, respectively). The response to hypoxia was assessed by changes in muscle pressure output (Pmus) and respiratory rate. Compared with the Pmus response at eucapnia (0.53 +/- 0.59 cm H2O/percentage oxygen saturation [% O2sat]), the response at mild hypocapnia was attenuated (0.26 +/- 0.33 cm H2O/% O2sat), whereas the response at moderate hypocapnia was negligible (0.003 +/- 0.09 cm H2O/% O2sat). Similar reductions were seen with the respiratory rate (eucapnia, 0.17 +/- 0.2 breaths/minute/% O2sat; mild hypocapnia, 0.11 +/- 0.11 breaths/minute/% O2sat; moderate hypocapnia, 0.01 +/- 0.06 breaths/minute/% O2sat). The Pmus and respiratory rate responses at the three levels of PETCO2 were significantly different (p < 0.05, analysis of variance). The responses at moderate hypocapnia were not significantly different from zero. We conclude that when apnea occurs under conditions in which central PCO2 is well below the CO2 setpoint, subjects are at risk of developing dangerous hypoxemia due to absence of a hypoxic ventilatory response.     

Effect of bronchial challenge on breathing patterns and arterial oxygenation in stable asthma

The effect of histamine or methacholine inhalational challenge on breathing patterns and oxygen saturation was investigated in ten stable asthmatic patients. We used the respiratory inductive plethysmograph to record respiratory timing and minute ventilation along with an ear oximeter to measure oxygen saturation (SaO2). As FEV1 fell during the challenge procedure, SaO2 also fell (average 3 percent). Furthermore, with histamine challenge, expiratory time (Te), inspiratory time (Ti), and breath period (Ttot) all increased; minute ventilation probably also fell. These changes in breathing pattern and SaO2 were reversed by inhalation of a beta 2-agonist. However, no such changes in breathing patterns were observed with methacholine challenge despite a similar fall in FEV1. Bronchial challenge produces hypoxia in stable asthmatic patients, which might result from a combination of hypoventilation with alteration in alveolar ventilation/perfusion relationships.     

Human obesity is characterized by a selective potentiation of central chemoreflex sensitivity.

The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Obesity is associated with an increased risk of alveolar hypoventilation and carbon dioxide retention, suggesting that abnormalities in chemoreflex control mechanisms may be implicated. We tested the hypothesis that chemoreflex function is altered in obesity. We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypercapnia, hypoxia, and the cold pressor test in 14 obese subjects and 14 normal-weight subjects matched for age and gender. During hypercapnia, the increase in minute ventilation was significantly greater in obese subjects (7.0+/-0.3 L/min) than in normal-weight subjects (3.3+/-1.1 L/min; P=0.03). Despite higher minute ventilation during hypercapnia in obese subjects, the increase in muscle sympathetic nerve activity was similar in obese and normal-weight subjects. When the inhibitory influence of breathing during hypercapnia was eliminated by apnea, the increase in sympathetic nerve activity in obese subjects (99+/-16%) was greater than in normal-weight subjects (44+/-16%; P=0.02). The magnitude of the ventilatory and autonomic responses to hypoxia and the cold pressor test was similar in obese and normal-weight subjects. We conclude that chemoreflex responses to hypercapnia are potentiated in eucapnic obese subjects. In contrast, responses to hypoxia and to the excitatory cold pressor stimulus in obese subjects are similar to those in normal-weight subjects. Thus, obesity is characterized by selective potentiation of central chemoreflex sensitivity.     

Chemosensitivity and breathing pattern regulation of the coatimundi and woodchuck.

An analysis of breathing pattern regulation was carried out on the coatimundi and woodchuck who represent two different volume-time patterns. It was found that the coati, with a short expiratory time as a fraction of total breath time, TE/TTOT, has a greater sensitivity to CO2 as represented by the slope and threshold of its ventilatory response. Breathing air the coati maintains post-inspiratory inspiratory activity (PIIA) of the posterior cricoarytenoid (PCA) through 51% of expiration, while the woodchuck, who is less sensitive to CO2 and has a long TE/TTOT, exhibits no PIIA of the PCA. The woodchuck also has a greater incidence and duration of end-expiratory pauses (or delayed inspiratory onset). The woodchuck does not demonstrate the usual inverse relationship between VT and TE in response to 5% CO2 and does not recruit PIIA of the PCA at this level of CO2. These data confirm the importance of CO2 chemosensitivity in regulation of TE. It is further demonstrated that interspecific differences in chemosensitivity among three mammals of the same size are reflected in regulation of TE but not in inspiratory 'drive' (as indicated by mean inspiratory flow, VT/TI).     

Hypercapnic and hypoxic ventilatory responses in parents and siblings of children with congenital central hypoventilation syndrome

Children with congenital central hypoventilation syndrome (CCHS) have abnormal ventilatory responses to metabolic stimuli. As there is a genetically determined component of chemoreceptor sensitivity, parents and siblings of children with CCHS may also have blunted ventilatory responses to hypercapnea and hypoxia. To test this, we studied hypercapnic ventilatory responses and hypoxic ventilatory responses in six mothers, four fathers, and five siblings (6 to 49 yr of age) of seven children with CCHS and compared them with 15 age- and sex-matched control subjects (5 to 47 yr of age). Pulmonary function tests were not different between relatives of children with CCHS and control subjects. To measure hypercapnic ventilatory responses, subjects rebreathed 5% CO2/95% O2 until PACO2 reached 60 to 70 mm Hg. To measure hypoxic ventilatory responses (L/min/% SaO2), subjects rebreathed 14% O2/7% CO2/balance N2 at mixed venous PCO2 until SaO2 fell to 75%. All tests were completed in less than 4 min. Instantaneous minute ventilation, mean inspiratory flow (tidal volume/inspiratory time), and respiratory timing (inspiratory timing/total respiratory cycle timing) were calculated on a breath-by-breath basis. Hypercapnic ventilatory responses were 1.97 +/- 0.32 L/min/mm Hg PACO2 in children with CCHS relatives and 2.23 +/- 0.23 L/min/mm Hg PACO2 in control subjects. Hypoxic ventilatory responses were -1.99 +/- 0.37 L/min/% SaO2 in the relatives and -1.54 +/- 0.25 L/min/% SaO2 in the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavior of expiratory neurons in response to mechanical and chemical loading.

The response of medullary expiratory neurons to added mechanical and chemical loads was studied in anesthetized cats. Alterations in burst characteristics and central timing were compared in the intact and bilaterally vagotomized cat. The following results were obtained: (1) Graded expiratory airflow resistances caused progressive increases in burst duration, spikes per burst and firing rate; similar effects were noted for end-inspiratory tracheal occlusions and continuous positive breathing; all facilitation was eliminated by vagotomy. (2) Graded inspiratory airflow resistances delayed the onset of an expiratory burst but did not change the overall burst characteristics. (3) Acute hypercapnia increased ventilation without noticeable changes in expiratory burst characteristics; acute hypoxia produced a reduction in burst duration concomitant with changes in ventilation. It is concluded that (1) expiratory neurons are responsive to vagally mediated volume information and (2) transient hypoxia and hypercapnia sufficient to increase ventilation does not increase the firing rate of expiratory neurons but exerts differential effects with respect to timing. It is suggested that expiratory duration is related to the time integral of expired volume and that the increase in FRC imposed by expiratory loads does not alter the central timing of the next inspiration.     

Control of breathing in chronic obstructive pulmonary disease patients at rest and after beta-2 agonist inhalation.

Ventilatory function tests, ventilatory cycle analysis, mouth occlusion pressure (P0.1) and effective inspiratory impedance (P0.1/Vt/Ti) were measured in 11 healthy subjects and in 26 patients with chronic obstructive pulmonary disease (COPD). In COPD patients these measurements were repeated 20 min after inhalation of 400 micrograms of fenoterol. In patients we observed an increase of mean inspiratory flow (Vt/Ti), and a decrease of inspiratory time (Ti) and inspiratory duty cycle (Ti/Ttot). P0.1 and effective inspiratory impedance were significantly increased. Moreover, we found a direct correlation between forced expiratory volume in 1 s (FEV1) and ventilatory cycle components (Ti/Ttot, Ti) and an indirect correlation between FEV1 and Vt/Ti.P0.1 was directly correlated with Vt/Ti and indirectly correlated with ventilatory cycle components. These observations lead us to speculate on the possible role of two opposite mechanisms acting on the control of breathing of COPD patients. While the 'intensity' component of the ventilatory cycle would be set to maintain the tidal volume at a constant level, the 'timing' component would act in order to prevent inspiratory muscle fatigue. Furthermore, in patients responsive to beta 2-agonist drugs, fenoterol inhalation would act in synergy with the timing component of ventilatory cycle, lowering P0.1 and the effective inspiratory impedance.     

Effects of hypoxemia on phrenic nerve responses to static lung inflation in anesthetized dogs

To study interactions between hypoxemia and lung stretch in modulating ventilatory activity, an experimental preparation was used that allows independent control of static airway pressure (Paw) and arterial PO2 in anesthetized dogs. Phrenic burst frequency (f) and integrated amplitude (Phr) were monitored while Paw was varied between 2 and 12 cm H2O at levels of PaO2 between 30 and 200 mm Hg. Experiments were repeated in intact (n = 8) and carotid denervated dogs (CBX; n = 7). In intact dogs, f decreased with increasing Paw through an effect on the expiratory duration (TE). Hypoxia increased f by decreasing both the inspiratory duration (TI) and TE. Hypoxia had no effect on the slope of the f vs Paw relationship, but attenuated the effect of Paw on TE. Phr was increased by hypoxia, but Paw had little effect. After CBX, f was still inhibited by Paw, but PaO2 had no consistent effect on f, TI or TE at any level of Paw. Phr was inhibited by hypoxia after CBX, but Paw had no effect. The results indicate that Paw and PaO2 exert additive effects on f in anesthetized dogs. Hypoxia attenuates the effect of Paw on TE, which alone would attenuate the slope of the f vs Paw relationship. However, the effect of hypoxia on TI enhances the slope of the f vs Paw relationship, restoring a parallel shift. These effects are abolished by carotid denervation.     

Effect of chlormadinone acetate on ventilatory control in patients with chronic obstructive pulmonary disease

Twelve patients with chronic obstructive pulmonary disease (COPD) were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, on chemical and neuromechanical respiratory controls and pulmonary gas exchange. Using a randomized, double-blind, cross-over trial, 1 wk of CMA therapy caused a significant reduction in arterial CO2 tension (Paco2) by 4.6 +/- 0.6 (SE) mmHg. This Paco2 fall was associated with increased minute ventilation (Vl), tidal volume (VT), and mean inspiratory flow (VT/Tl). During CMA administration, occlusion pressure response to CO2 with and without inspiratory flow-resistive loading increased significantly (p less than 0.01) over that during placebo administration, whereas ventilatory response to CO2 did not. In addition, normocapnic ventilatory and occlusion pressure response to hypoxia were significantly elevated (p less than 0.01) during CMA therapy. Furthermore, the degree of load compensation, which was assessed by the ratio of the loaded to unloaded slope in the occlusion pressure response to CO2, increased in all subjects after CMA administration. These results indicate that CMA augments not only the respiratory neuromuscular response to hypercapnia and hypoxia, but also flow-resistive load compensation in patients with COPD, and it may provide support for the use of CMA in patients who are able to decrease their Paco2 with this agent.     

Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases.

The hypothesis that, in neuromuscular and chest wall diseases, improvement in central respiratory drive explains the effects of night-time ventilation on diurnal gas exchanges was tested. The effects at 6 months, 1, 2 and 3 yrs of intermittent positive pressure ventilation (IPPV) on arterial blood gas tension, pulmonary function, muscle strength, sleep parameters, respiratory parameters during sleep and ventilatory response to CO2 were evaluated in 16 consecutive patients with neuromuscular or chest wall disorders. As compared with baseline, after IPPV daytime arterial oxygen tension (Pa,O2) increased (+2.3 kPa at peak effect) and arterial carbon dioxide tension (Pa,CO2) and total bicarbonate decreased (-1.8 kPa and -5 mmol x L(-1), respectively) significantly; vital capacity, total lung capacity, maximal inspiratory and expiratory pressures and alveolar-arterial oxygen gradient did not change; the apnoea-hypo-opnoea index and the time spent with an arterial oxygen saturation (Sa,O2) value <90% decreased (-24 and -101 min, respectively), sleep efficiency and mean Sa,O2 increased (+16% and +5%, respectively); and ventilatory response to CO2 increased (+4.56 L x min(-1) x kPa(-1)) significantly. The reduction in Pa,CO2 observed after IPPV correlated solely with the increase in the slope of ventilatory response to the CO2 curve (r=-0.68, p=0.008). In neuromuscular or chest wall diseases, improvement of daytime hypoventilation with nocturnal intermittent positive pressure ventilation may represent an adaptation of the central chemoreceptors to the reduction of profound hypercapnia during sleep or reflect change in the quality of sleep.     

Expiratory pattern and laryngeal responses to single-breath expiratory resistance loads

Responses of expiratory duration (TE) and laryngeal aperture to small flow resistance loads (2 and 5 cm H2O/LPS) applied to single expirations were measured using repeated applications in four subjects during quiet breathing. All subjects significantly prolonged TE in response to the higher load and 3 of the 4 showed that same response to the lower load, which was not perceived by these subjects. These same 3 subjects showed a narrowed laryngeal aperture in response to loading such that their expiratory impedance must have been greater than the increase provided by the load alone. The effect of such a loading response was to slow the expiratory volume decay so that a small but significant increase in the halftime for volume decay was observed. The prolongation of TE seen with loading could be due to the alteration of volume-related feedback consequent to the increased expiratory impedance. This may serve a role in regulation of expiratory muscle function.     

Gender-specific effects of CNQX administered into the arcuate nucleus on ventilatory patterns in rats.

This study evaluated the effect of microinjection of the non-N-methyl-D-aspartate (NMDA) receptor antagonist, cyano, 3-dihydro-7-nitrogluinoxaline-2, 3-dione (CNQX), into the arcuate nucleus of the hypothalamus on ventilation in male and female rats. Conscious rats received saline or 50, 100, or 200 pmol concentrations of CNQX on separate days. Significant interactions between dose and gender were observed on frequency, inspiratory (TI) and expiratory (TE) time, and tidal volume. CNQX depressed frequency, but increased tidal volume in female rats. Effects of CNQX in males on these ventilatory parameters were considerably less. In CNQX-treated females the decrease in frequency of breathing was primarily due to an increase in TI. Exposure of CNQX-treated female rats to hypercapnia, but not to hypoxia transiently decreased TI. No effect of CNQX was noted on oxygen consumption or body temperature. Thus, non-NMDA receptors in the arcuate nucleus are involved in modulating ventilatory patterns in a gender-specific manner independent of its effects on oxygen consumption or body temperature.