Analysis of respiratory patterns in the awake and in the halothane anaesthetised rat

Respiratory patterns have been studied in awake and halothane anaesthetised rats. Tidal volume (VT) was shown to be age-sensitive over 44-200 days; failure to account for this gave the appearance of an increased ventilatory sensitivity to CO2 with age. Inspiration of CO2 (0-10.5%) produced linear responses of VT whereas frequency responses stabilised at 6% CO2. Initially expiratory duration (TE) decreased more than inspiratory duration (TI) and both decreased linearly relative to increased VT; above 6% CO2, increases in VT occurred with only minor changes in TI and TE. Halothane anaesthesia dominantly depressed the frequency response to CO2. We conclude that the rat shows a great influence of vagal control on breathing in the awake state and in halothane anaesthesia; that TE is controlled independently of TI; and that respiratory frequency is more rigorously controlled than VT.     

The effect of rebreathing CO2 on ventilation and diaphragmatic electromyography in newborn infants

We tested the hypothesis of whether the reduced ventilatory response to CO2 in preterm as compared to term infants is related to primary central unresponsiveness, or to mechanical impairment of the respiratory pump. Eleven preterm (n = 19; gestational age 32 +/- 0.4 wk) and 14 term (n = 24; GA 40 +/- 0.3 wk) infants were studied. Minute integrated diaphragmatic activity EMGDi X f), and mean inspiratory diaphragmatic activity (EMGDi/TI), were used as indices of central output. After 3 min breathing 21% O2 (control), infants rebreathed from a bag containing 5% CO2 in 40% O2 for 2 to 3 minutes. We measured VE, VT, f, VT/TI. Sleep states were monitored. Preterm infants had a decreased ventilatory response to CO2 both in quiet sleep (QS) (0.0379 +/- 0.067 vs 0.505 +/- 0.032 L . (min . kg . kPa PACO2)-1; P less than 0.04) and in active sleep (AS) (0.210 +/- 0.032 vs 0.331 +/- 0.048 L . (min . kg . kPa PACO2)-1; P less than 0.04). The decrease in response primarily was a function of a lack of increase in tidal volume with CO2 in QS and a lack of increase in f in AS. Parallel to these changes there were significant correlations between the increases in EMGDi X f and VE with inhaled CO2 (r = 0.75; P less than 0.001); VT and EMGDi (r = 0.63; P less than 0.01); and between the increases in EMGDi/TI and VT/TI with inhaled CO2 (r = 0.64; P less than 0.001). The results suggest that ventilatory response to CO2 is (1) correlated highly with diaphragmatic indices of central output; (2) less in active than in quiet sleep; (3) less in preterm than in term infants. We conclude that despite their increased chest wall compliance, preterm infant respond less to CO2 because of central unresponsiveness.     

Control of breathing in patients with myasthenia gravis.

Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon, and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/VC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p less than 0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p less than 0.001), VT (p less than 0.001), VT/TI, (p less than 0.003), P0.1 (p less than 0.003), and EMGd (p less than 0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p less than 0.005), MIP (p less than 0.02), and MEP (p less than 0.01) significantly increased, whereas spontaneous breathing remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing pattern and occlusion pressure during exercise in pre- and peripubertal swimmers

In two groups of young swimmers (prepubertal stage: group A; peripubertal stage: group B), the ventilatory response to graded exercise work with a cycle ergometer was studied. Ventilatory variables (ventilation, VE, tidal volume, VT, respiratory frequency,f, ratio between inspiratory period and total breath duration, TI/TTOT, and mean inspiratory flow, VT/TI) as well as mouth occlusion pressure measured at 100 msec (P0.1), effective impedance of the respiratory system (P0.1/VT/TI), inspiratory power for breathing (W) and O2 uptake (VO2) were measured during the third minute of each work load. At the same level of exercise both groups showed identical values of VT/TI, but VE was higher in group A individuals. This resulted from higher values of respiratory frequency with higher TI/TTOT ratios. P0.1, P0.1(VT/TI) and W were also much higher during work load in group A than in peripubertal subjects. When the above results were related to the same percentage of VO2 max, P0.1, W, respiratory frequency and duty cycle did not differ within both groups. However, VE, VT and VT/TI were lower in group A subjects with a higher P0.1/(VT/TI) ratio. Further corrections of VT, VT/TI and P0.1/(VT/TI) ratios by body weight cancelled all these differences. In conclusion, our results strongly suggest that biometric factors only determined interindividual differences in ventilatory response to exercise in prepubertal and peripubertal swimmers.     

The pattern of resting breathing in patients with upper airway obstruction

The flow-time curve of resting breathing was recorded in 14 patients (aged 36 +/- 16 yrs) with mild to moderate symptoms of upper airway obstruction (UawO) and compared to that of 28 matched, healthy controls (HC) in order to characterize the breathing pattern of such patients. The inspiratory time over total time (TI/Ttot) was higher in the patients (0.42; SD 0.04) than in HC (0.37; SD 0.04) (p less than 0.001), and tidal volume (VT) over TI was lower in patients (0.37; SD 0.07 l.s-1) than in HC (0.43; SD 0.09 l.s-1) (p less than 0.01). Inspiratory and expiratory peak flows at rest were also lower in the patients (p less than 0.001). In these, the mean to peak flow ratio of inspiration (0.74; SD 0.07) was higher than in HC (0.66; SD 0.04) (p less than 0.0005). This indicates a more rectangular wave of inspiration in the patients. All of these changes may be due to the increased inspiratory load. However, since the patients were breathing at rest with VT and flows far below their values on the maximal flow volume loop, the changes can also be interpreted as adaptive rather than imposed by absolute mechanical limitations.     

Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction

The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of beta-adrenergic blockade on P0.1 and mean inspiratory flow

To quantitatively examine and compare the effects of beta-adrenergic blockade on ventilation, we studied 20 healthy volunteers during inhalation of room air and at steady state CO2 (2.0, 4.4, 6.0%) following a single oral dose of bupranolol (vs. placebo). During room air breathing, minute ventilation (VE) and mean inspiratory flow (VT/TI) were significantly reduced after beta-blockade with a concomitant increase in blood PaCO2 (p less than 0.01). The timing factor TI/Ttot and mouth occlusion pressure P0.1 remained unchanged. These differences were, as shown from calculated effective alveolar ventilation, mainly attributed to a decrease in physiological dead space ventilation following beta-blockade. With a stepwise increase in FICO2, the difference in PaCO2 between placebo and bupranolol tended to approach zero, whereas VE and VT/TI remained significantly lower during beta-blockade (P less than 0.05). In contrast, no difference existed in P0.1 between bupranolol and placebo. We suggest that (1) respiratory drive assessed by P0.1 is unaffected by beta-blockade and (2) mean inspiratory flow depends also on CO2 elimination characteristics, which are influenced by beta-blockade.     

Effect of posture on ventilation and breathing pattern during room air breathing at rest

We measured minute ventilation (VE), tidal volume (VT), mean inspiratory flow (VT/TI), and occlusion pressure (P.1) in 10 resting subjects breathing room air, in sitting, supine, right and left lateral positions, and compared them with corresponding data on static lung compliance [Cst(l)], dynamic lung compliance [Cdyn(l)], and pulmonary flow resistance [R(l)]. Highest values for VT, VE, VT/TI, P.1, and effective inspiratory impedance [P.1/(VT/Ti)] were observed in the supine posture. Values for P.1 and P.1/(VT/TI in lateral decubitus were intermediate to those obtained when seated and supine. While the increases in P.1 and P.1/(VT/TI) in recumbent postures were qualitatively similar to the decrease in Cdyn(l) and increase in R(l), there was no significant correlation between them, probably reflecting the complex relationship between P.1/(VT/TI) and lung compliance and resistance, as the former, in addition to lung mechanics, also depends on the shape of the inspiratory driving pressure wave, the active inspiratory impedance, the mechanics of the chest wall, and the duration of inspiration.     

Ventilatory drive and respiratory muscle function in pregnancy

It has been demonstrated that during pregnancy expiratory reserve volume (ERV) decreases and minute ventilation (VE) increases initially and then stabilizes. In order to determine the role of thoracoabdominal mechanics, control of breathing, and inspiratory muscle function in these alterations, we studied inspiratory pressures, lung volumes, thoracic configuration, and respiratory drive in 18 normal pregnant women at Weeks 13, 21, 30, and 37 of pregnancy. Ten of them were studied 6 months after delivery. Transdiaphragmatic pressure (Pdi) was measured at Week 37 and 3 months after delivery in an additional group of seven women. VE as well as VT/TI increased early during gestation and remained unchanged thereafter. In contrast, mouth occlusion pressure (P0.1) increased progressively during pregnancy, from 1.53 +/- 0.16 (mean +/- SE) to 2.02 +/- 0.18 cm H2O, and fell significantly to 1.1 +/- 0.15 cm H2O after delivery, indicating that effective respiratory impedance increases during pregnancy. Mean P0.1 correlated with progesterone plasma levels (r = 0.918 p less than 0.05). No changes in Plmax, PEmax, and Pdimax, were observed. End-expiratory gastric pressure (Pga) increases significantly during pregnancy: 11.8 +/- 0.8 versus 8.4 +/- 1.12 cm H2O after delivery (p less than 0.012). This increment was correlated with the fall in ERV observed in late pregnancy (r = 0.74 p less than 0.05). Our results demonstrate that during pregnancy ventilatory drive and respiratory impedance increase with the consequent stabilization of VE, but our data do not permit us to differentiate whether the increment in P0.1 is secondary to the increase in impedance or to the rise in progesterone. Respiratory muscle function remains normal despite the alteration of thoracic configuration.     

Differences in respiratory patterns after acute and chronic pulmonary denervation

The role of pulmonary vagal information in the control of respiratory patterns was assessed in awake and anaesthetised rats in which pulmonary denervation was effected by bilateral cervical vagotomy or by right cervical vagotomy combined with left pneumonectomy or left intrathoracic vagotomy. Acute denervation led to increases of tidal volume (VT), inspiratory duration (TI) and expiratory duration (TE) in both awake and halothane anaesthetised animals; in awake rats the increase of TE rapidly subsided. Chronic pulmonary denervation produced markedly smaller increases of VT and TI and no change of TE from control values. In hypercapnia, awake animals with combined pneumonectomy and vagotomy consistently increased respiratory frequency by reductions in TI and TE; awake animals with combined intrathoracic and cervical vagotomy showed no increase in f because decreases in TI offset increases in TE; in anaesthetised rats with acute bilateral cervical vagotomy there was a consistent fall in respiratory frequency due to an expiratory pause. The results demonstrate that (1) the role of vagal activity in the production of respiratory patterns is unlikely to be accounted for solely in terms of influences arising from pulmonary stretch receptors; (2) vagal influences of TE are transitory; (3) under halothane anaesthesia hypercapnia induces an expiratory pause; and (4) the combination of pneumonectomy with contralateral vagotomy makes possible studies in awake rats although pulmonary denervation is less complete than with bilateral intrathoracic vagotomy.     

The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation

We prospectively examined the pattern of breathing in patients being weaned from mechanical ventilation: one group (n = 10) underwent a successful weaning trial and were extubated, whereas another group (n = 7) developed respiratory failure and required the reinstitution of mechanical ventilation. During the period of ventilator support, minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were similar in the 2 groups. After discontinuation of the ventilator, VI remained similar in the 2 groups, but VT was lower and f was higher in the patients who failed the trial compared with those who were successful, 194 +/- 23 and 398 +/- 56 ml (p less than 0.001), respectively, and 32.3 +/- 2.3 and 20.9 +/- 2.8 breaths/min (p less than 0.001), respectively. The failure group displayed a significant increase in PaCO2 (p less than 0.005) during spontaneous breathing, without a concomitant increase in the alveolar-arterial PO2 difference. Eighty-one percent of the variance in PaCO2 was accounted for by the pattern of rapid, shallow breathing. During weaning, resting respiratory drive (reflected by mean inspiratory flow, VT/TI) and fractional inspiratory time (TI/Ttot) were similar in the 2 groups. The patients in the failure group showed significant increases in VT/TI, 265 +/- 27 to 328 +/- 32 ml/s (p less than 0.01), and VI, 5.82 +/- 0.53 to 7.32 +/- 0.52 L/min (p less than 0.01), from the beginning to the end of the weaning trial; VT and f showed no further change.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Airway occlusion pressure. An important indicator for successful weaning in patients with chronic obstructive pulmonary disease

The objective of this study was to determine whether airway occlusion pressure (P0.1) is a useful predictor for successful weaning during discontinuation of assisted ventilation (AV) in patients with chronic obstructive pulmonary disease (COPD). We studied 12 patients with COPD receiving AV with maximal inspiratory pressure (MIP) less than or equal to -20 cm H2O and FVC greater than or equal to 10 ml/kg. The P0.1, VT, frequency, mean inspiratory flow rate (VT/TI), inspiratory time to total breath cycle duration (TI/Ttot), and arterial blood gases were determined just prior to weaning, within 5 min after discontinuing AV (Time 0), and at 30, 60, 90, 120, 180, and 240 min. Five of the 12 patients failed to wean, defined as requiring AV within 24 h after discontinuing AV. At Time 0, all patients who subsequently failed to wean had a P0.1 of greater than 6 cm H2O, and those who were successfully weaned had a P0.1 of less than 6 cm H2O (p less than 0.001), although the arterial blood gas determinations were comparable in both groups. Throughout the study period, P0.1 in the patients who failed to wean was persistently higher than in the successfully weaned patients. Despite the high P0.1, VT and VT/TI decreased significantly at the termination of the study compared with those at Time 0 in 3 of the patients who failed to wean. Tachypnea was not useful in predicting failure to wean. The TI/Ttot in the patients who failed to wean was persistently lower than in the successfully weaned patients. We conclude that P0.1 is an important indicator for successful weaning.     

Inspiratory force reserve of the respiratory muscles in children with chronic obstructive pulmonary disease

The purpose of this study was to evaluate inspiratory muscle force reserve in children with chronic obstructive pulmonary disease (COPD). In 15 hyperinflated (FRC/TLC, 65 +/- 0.7%) children, maximal mouth inspiratory static pressure (PImax) at FRC, mouth occlusion pressure (P0.1), tidal volume (VT), inspiratory time (TI), and total duration of the respiratory cycle (Ttot) were all measured. It was found that PImax at FRC was reduced compared with predicted values. However, after lung volume correction, PImax was in the normal range, and P0.1 was higher, TI was shorter, and Ti/Ttot was lower than predicted. The estimated mean inspiratory pressure for breathing at rest (PI) was significantly higher than predicted and was related to total pulmonary resistance (r = 0.74, p less than 0.001). The fraction of PImax developed by the respiratory muscles for breathing at rest (PI/PImax) significantly increased. The higher the PI/PImax ratio, the more the TI/Ttot ratio decreased (r = -0.64, p = 0.01). At rest, our subjects had to develop a mean inspiratory power (W) of as much as 48% (range, 30 to 76%) of the critical W above which fatigue occurs. Thus, even minimal increases in breathing load might expose children with COPD to respiratory muscle fatigue and to respiratory failure.     

Breathing pattern during exercise in untrained children

Breathing pattern during exercise on a cycle ergometer was studied in 18 untrained children aged from 6 to 15 years of age (9 boys, 9 girls). Oxygen uptake, tidal volume, minute ventilation, all normalized for body weight (VO2BW, VT BW, VE BW), respiratory frequency (f), inspiratory (TI) and expiratory (TE) times, ratio TI over total duration of the respiratory cycle (TI/TTOT) and mean inspiratory flow (VT BW/TI) were measured: (1) at rest (W0) and at the highest load (maximal cardiac rate) of an incremental exercise (W1); (2) in steady state conditions, at 50% of W1 (W1/2) and at 2/3 of W1 (W2/3). VO2BW, VT BW, VE BW, TI/TTOT, VT BW/TI increased significantly (P less than 0.01) from W0 to W1. Behaviour of f and TI were different from the latter parameters: f increased and TI decreased significantly from W0 to W1/2 (P less than 0.01) and from W1/2 to W2/3 (P less than 0.01) but remained similar at W2/3 and W1. We observed a relationship between VO2 BW and VT BW/TI, and between VT BW and TI/TTOT at each step of workload. We conclude that untrained children adapt the pattern of breathing during exercise, as at rest, to metabolic demand. However, the increase in f and the decrease in TI are limited at maximal workload.     

Alcohol and the response of upper airway resistance to a changing respiratory drive in normal man

We studied the effects of alcohol ingestion on the response of upper airway resistance (UAR) to changing respiratory motor output in 9 normal subjects. Nasal and pharyngeal pressures were measured with two low bias flow catheters placed at the tip of the epiglottis and in the posterior nasopharynx. Respiratory flow was measured with a Fleisch no. 3 pneumotachograph connected to a tightly fitting mask. Breath-by-breath inspiratory upper airway resistances were calculated at isoflow during 1) a CO2 rebreathing (increase in drive), 2) 2 min following five slow vital capacities of 100% O2 (decrease in drive) (Post-O2 period), and 3) 1 min before each procedure (baseline measurements). The respiratory motor output was estimated by the pressure developed 0.1 sec after the onset of inspiration (P0.1) during rebreathing and by the mean inspiratory flow (VT/TI) during the post-O2 period. Measurements were performed before and after the ingestion of 1.5 ml/kg of 40% alcohol. Blood alcohol level rose from 0 to 14.9 +/- 1.8 mmol.L-1 (Mean +/- SD) and total supralaryngeal resistance increased from 2.8 +/- 1.8 cm H2O.L-1.sec to 4.2 +/- 1.8 cm H2O.L-1.sec (P less than 0.001, Student's paired t-test). During CO2 rebreathing UAR decreased exponentially as P0.1 increased both before and after alcohol intake. The slope of the plot Log (pharyngeal resistance) against P0.1 decreased from -17.0 x 10(-3) +/- 9.3 x 10(-3) before alcohol to -11.0 x 10(-3) +/- 6.6 x 10(-3) after alcohol intake (P = 0.03). The slope of the decrease in nasal resistance remained unchanged. A decrease in VT/TI occurred during the Post-O2 period and was accompanied by an exponential increase in UAR at each experiment. The slope of Log (pharyngeal resistance) over VT/TI was significantly higher after (-27.0 x 10(-3) +/- 7.1 x 10(-3)) than before alcohol (-12.0 x 10(-3) +/- 4.2 x 10(-3), P less than 0.001). The slope of the increase in nasal resistance with decreasing VT/TI rose from -8.4 x 10(-3) +/- 6.5 x 10(-3) to -13.0 x 10(-3) +/- 7.4 x 10(-3) after alcohol ingestion (P = 0.06). We conclude that alcohol ingestion depresses the pharyngeal responses to changing central drive in normal subjects.     

Control of breathing in patients with chronic obstructive lung diseases and secondary polycythemia after venesection

Using the mouth occlusion pressure technique, we have studied the control of breathing in 10 hypercapnic patients with chronic obstructive pulmonary diseases and polycythemia before and after venesection. The mean hematocrit value was 59.9 +/- 5.5% which, following venesection (approximately 1,200-1,600 cm3 of blood was removed from each patient over three consecutive days), fell to 44.4 +/- 2.2%. Respiratory drive, expressed as P0.1 (mouth occlusion pressure 0.1 s after the onset of occluded inspiration at functional residual capacity) and as mean inspired flow (VT/TI), was diminished after venesection (p less than 0.001 and p less than 0.05); in contrast to that, we found no changes in respiratory timing (TI and TI/Ttot). The arterial PCO2 was decreased (p less than 0.001) and arterial PO2 was increased after venesection, these improvements are mainly attributed to decreased dead space ventilation (p less than 0.05). It seems that the improvements of blood gases after venesection is probably responsible for the decrease in respiratory drive.     

Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspiratory impedance during histamine-induced bronchoconstriction in patients with bronchial asthma

Histamine inhalation provocation tests were performed in 18 asymptomatic asthmatic patients with progressively increasing doses of a pressurized aerosol of histamine phosphate. Forced expiratory volume in 1 s (FEV1), total neuromuscular output, assessed by mouth occlusion pressure (P0.1), mean inspiratory flow (VT/Ti), and the P0.1/(VT/Ti) ratio, which represents an index of effective inspiratory impedance of the respiratory system, were measured. With histamine, compared to control, FEV1 decreased and P0.1/(VT/Ti) increased (p less than 0.01 for both). After bronchoconstriction was reversed by administration of a beta 2-agonist bronchodilator (fenoterol), a significant decrease in P0.1/(VT/Ti) (p less than 0.001) and a significant increase in FEV1 (p less than 0.01) were noted as compared to histamine. With histamine, change in P0.1/(VT/Ti) was found to be related to its pre-histamine value (p less than 0.01). Furthermore, with histamine and fenoterol, changes in P0.1/(VT/Ti) and concurrent changes in FEV1 were found to be significantly related (p less than 0.001). From these data we calculated that the P0.1/(VT/Ti) ratio provides a useful tool in the clinical assessment of histamine-induced bronchospasm.     

The effects of chronic airflow limitation, increased dead space, and the pattern of ventilation on gas exchange during maximal exercise in advanced cystic fibrosis

Although exertional hypercapnea has been observed in patients with advanced cystic fibrosis (CF), the causes have not been fully elucidated. In 14 patients aged 15 to 35 yr of age with advanced CF, the effects of chronic airflow limitation (CAL), increased physiologic dead space (VD), and the timing components of ventilation (VE) on gas exchange during maximal exercise were assessed. The patients were divided into those who retained CO2 during exercise, the CO2R group, and those who did not, the CO2NR group. CO2 retention was defined as a rise in end-tidal CO2 tension of 5 mm Hg or more or to a value greater than 50 mm Hg during a progressive exercise test on a cycle ergometer. CO2 retention occurred in half the subjects, usually by the halfway mark of the test, and did not rise progressively as exercise continued. It was associated with a low VE caused by a low tidal volume (VT) that was the result of a short inspiratory time to total respiratory time ratio (0.33 +/- 0.03 versus 0.38 +/- 0.04, p less than 0.02), whereas there was no difference in mean inspiratory flow or respiratory rate. Although the CO2R group had the worst CAL, with a FEV1 of 28 +/- 7 versus 41 +/- 12% predicted (p less than 0.5) and a FVC of 42 +/- 12 versus 61 +/- 9% predicted (p less than 0.01), the VT at maximal work expressed as a percentage of FVC was lower (45 +/- 13 versus 60 +/- 11, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)