Density dependence of maximal flow is lung volume dependent during bronchoconstriction.

We examined the changes in maximum expiratory flow (Vmax) and the density dependence of maximum expiratory flow (delta Vmax) during histamine-induced bronchoconstriction in dogs. Histamine acid phosphate solution was nebulized into the airways of six dogs to produce predominantly peripheral airway obstruction. Vmax air, Vmax with the dogs breathing 80% He-20% O2 (delta Vmax), and airway sites of flow limitation (choke points) were examined at four lung volumes (VL), which ranged from 51 to 23% of the control vital capacity (VC). The findings were interpreted in terms of the wave-speed theory of flow limitation. At all VL, Vmax air decreased during bronchoconstriction by approximately 30% compared with the control value. Resistances peripheral to a 0.3-cm-diam airway were increased about threefold with histamine, whereas resistances between 0.6-cm-diam bronchi and main-stem bronchi increased just slightly. Airway diameters were measured in the air-dried lung at 20 cmH2O transpulmonary pressure. Our results showed that only at 44% VC did delta Vmax decrease in all experiments after histamine to indicate peripheral obstruction (mean: 68.5 to 45%). At 23% VC, delta Vmax increased slightly, from 22 to 28%. At 23 and 36% VC, substantial differences in the wave-speed variables between air and HeO2 were present before bronchoconstriction, so that delta Vmax was low in some dogs, although peripheral airway obstruction was not evident. When bronchoconstriction was produced, delta Vmax at 23% VC could not be decreased further and even increased in four of six dogs. Thus changes in delta Vmax at given lung volume may not reflect the predominant site of airflow obstruction during bronchoconstriction.

Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth.

We examined the mechanism of the reduced maximum expiratory flow rates (Vmax) in a dog model of postpneumonectomy compensatory lung growth. During forced expiration, a Pitot-static tube was used to locate the airway site of flow limitation, or choke point, and to measure dynamic intrabronchial pressures. The factors determining Vmax were calculated and the results analyzed in terms of the wave-speed theory of flow limitation. Measurements were made at multiple lung volumes and during ventilation both with air and with HeO2. Five of the puppies had undergone a left pneumonectomy at 10 wk of age, and 5 littermate controls had undergone a sham operation. All dogs were studied at 26 wk of age, at which time compensatory lung growth had occurred in the postpneumonectomy group. Vmax was markedly decreased in the postpneumonectomy group compared with control, averaging 42% of the control flow rates from 58 to 35% of the vital capacity (VC). At 23% of the VC, Vmax was 15% less than control. Choke points were more peripheral in the postpneumonectomy dogs compared with controls at all volumes. The total airway pressure was the same at the choke-point airway in the postpneumonectomy dogs as that in the same airway in the control dogs, suggesting that the airways of the postpneumonectomy dogs displayed different bronchial area-pressure behavior from the control dogs. Despite the decreased Vmax on both air and HeO2, the density dependence of flow was high in the postpneumonectomy dogs and the same as controls at all lung volumes examined.

Effects of upper or lower airway anesthesia on hypercapnic ventilation in humans.

To evaluate the contribution of vagal airway receptors to ventilatory control during hypercapnia, we studied 11 normal humans. Airway receptor block was induced by inhaling an aerosol of lidocaine; a preferential upper oropharyngeal block was also induced in a subgroup by gargling a solution of the anesthetic. Inhalation of lidocaine aerosol adequate to increase cough threshold, as measured by citric acid, did not change the ventilatory response to CO2, ratio of the change in minute ventilation to change in alveolar PCO2 (delta VI/delta PACO2), compared with saline control. Breathing pattern at mean CO2-stimulated ventilation of 25 l/min showed significantly decreased respiratory frequency, increased tidal volume, and prolonged inspiratory time compared with saline. Resting breathing pattern also showed significantly increased tidal volume and inspiratory time. In nine of the same subjects gargling a lidocaine solution adequate to extinguish gag response without altering cough threshold did not change delta VI/delta PACO2 or ventilatory pattern during CO2-stimulated or resting ventilation compared with saline. These results suggest that lower but not upper oropharyngeal vagal airway receptors modulate breathing pattern during hypercapnic as well as resting ventilation but do not affect delta VI/delta PACO2.

Dynamic lung function in dogs with compensatory lung growth.

Nine puppies underwent left pneumonectomy at 10 wk of age while nine sex-matched littermates had a sham operation, and all animals were studied at 25 wk of age. Postpneumonectomy dogs demonstrated compensatory growth in that lung weight and total lung capacity (TLC) were the same as those of control animals when normalized for body weight. In postpneumonectomy dogs all lobes of the remaining right lung increased in weight, but this was most notable in the cardiac lobe which grew across the mediastinum. Subdivisions of lung volume were normal in postpneumonectomy animals except for residual volume (RV): RV/TLC was increased when compared with control animals. In intact dogs static pressure-volume curves of the lung and respiratory system did not differ between groups, and the static pressure-volume curves of excised lungs were closely similar. Maximum expiratory flow was sharply reduced in postpneumonectomy dogs, averaging 40% of flow in control dogs over the lower 50% of the vital capacity. In both groups the fractional increase in maximal expiratory flow during HeO2 breathing was substantial and similar. Regional compliances, resistances, and perfusion distribution were examined using 133Xe. Regional compliance and perfusion were reduced in the left hemithorax of postpneumonectomy dogs while regional resistances were increased.

Familial aspects of ventilatory control in patients with chronic obstructive pulmonary disease.

To determine whether abnormal chemical drives to breathe in patients with chronic obstructive pulmonary disease (COPD) antedate the development of chronic CO2 retention, we measured ventilatory and P0.1 responses to hypercapnia and hypoxia in 14 such patients and 23 of their normal adult offspring. Hypoxic responses in the patients were positively correlated with the mean hypoxic responses of their offspring. Neither the hypercapnic responses nor the resting breathing patterns of the patients were related to those of their offspring. Hypoxic response was lower in offspring of hypercapnic patients than in offspring of normocapnic patients. Blunt hypoxic responses in patients with COPD are influenced by familial factors and may represent a premorbid "risk factor" in the development of CO2 retention in this disease. This does not appear to be true for hypercapnic response or breathing pattern.

Ventilatory control after pulmonary resection.

Because pulmonary resection decreases pulmonary compliance, the effects of resection on ventilation might be similar to the known effects of elastic loading. We evaluated the breathing pattern and ventilatory drive in 12 patients before and after pulmonary resection with mean tissue loss of 4 segments. During resting ventilation, the only significant change after resection was a decrease in inspiratory time (Tl). At a higher level of minute ventilation (VE), induced by CO2 rebreathing, significant changes included increased respiratory frequency, decreased tidal volume and Tl, and increased occlusion pressure (P0.1). Both ventilation and occlusion pressure responses to CO2 (delta VE/delta PACO2, delta P0.1/delta PACO2) were unchanged after resection. We conclude that increased ventilation induced by CO2 rebreathing unmasks a breathing pattern after pulmonary resection which is similar to that seen with breathing against an external elastic load.

Effects of cold air hyperpnea in patients with chronic obstructive lung disease.

In 26 well-characterized, stable patients with chronic obstructive pulmonary disease (COPD), we measured changes in forced expiratory volume in one second (FEV1) induced by isocapnic hyperpnea of subfreezing dry air. The patients had a mean FEV1 of 1.21 L(38% predicted); 13 of 26 increased their FEV1 by at least 20% in response to inhaled beta agonists, and 11 of 18 subjects tested demonstrated at least a 30% increase in FEV1 with oral administration of corticosteroids. Only 6 of 26 patients responded to cold air hyperpnea with a 20% decrease in FEV1. Cold air response was not related to baseline FEV1 or to the level of hyperpnea attained. Though responses to inhaled beta agonists and systemic steroids were correlated, neither correlated with cold air responses. We conclude that in COPD airway reactivity is not nonspecific but depends on the agent used to elicit airway responses.

Lobar blood flow, blood volume and water content in atelectasis.

In nine intact supine anesthetized dogs we measured pulmonary blood flow distribution, lobar hemoglobin content, and lobar wet wt/dry wt during left lower lobe collapse. The animals breathed a mixture of 88% O2/12% N2 and atelectasis was induced by occluding the left lower lobe bronchus. Lobar volume was assessed by measuring lobar N2 concentrations. Using the radioactive microsphere technique, perfusion distribution was measured at lobar volumes of 50% FRC and 18-25% FRC. Hemoglobin content and wet wt/dry wt were measured at the latter volume. At 50% FRC lobar blood flow was unchanged though lobar pressure was negative. At the lower volume lobar blood flow averaged 72% of that at FRC, and lobar hemoglobin content was similar to that of the right lower lobe, indicating that lobar blood volume was unchanged. Wet wt/dry wt was significantly less in collapsed left lower lobes than in control right lower lobes, perhaps indicating that pressure in fluid-exchanging vessels was less than interstitial pressure during atelectasis.

Response to external inspiratory resistive loading and bronchospasm in anesthetized dogs.

Mouth occlusion pressure (P0.1) and breathing-pattern responses to external inspiratory resistive loading and methacholine chloride-induced bronchospasm were assessed in six dogs under pentobarbital sodium anesthesia. There was no change in P0.1 with external loading, but, in response to bronchospasm, we observed a P0.1 increase proportional to the change in lung resistance. These results indicate that, unlike external loading, the ventilatory-drive adaptation to bronchospasm does not require consciousness of the animal. The breathing-pattern response to bronchospasm consisted of tachypnea associated with decreased tidal volume (VT), decreased inspiratory duration (TI), and unchanged mean inspiratory flow (VT/TI). In response to resistive loading there was no tachypnea, VT decreased, TI was unchanged, and VT/TI decreased. We suggest that in response to resistive loading there was no modification of vagal activity, whereas in bronchospasm there was an increase of vagal activity, which was responsible for the changes in breathing pattern and, at least in part, for the changes in P0.1.

Airway anesthesia and respiratory response to methylcholine induced bronchoconstriction.

P0.1 and breathing pattern in response to acute methylcholine induced bronchoconstriction were studied with and without previous airway anesthesia in 6 normal subjects. In a randomized cross-over study, on two successive days, the subjects inhaled either 4% lidocaine hydrochloride or isotonic saline for 12 min, and then methylcholine for 3 min. FEV1, P0.1, and breathing patterns were measured at baseline and following each inhalation. Baseline values were changed neither by saline, nor by lidocaine, and methylcholine induced the same 18% decrease in FEV1 after each agent. Bronchospasm was not accompanied by a change in PACO2. After saline, methylcholine bronchospasm was associated with an increase of P0.1 from 1.0 +/- 0.2 (SEM) to 1.8 cm H2O +/- 0.3 (SEM) (P less than 0.05). During bronchospasm following airway anesthesia. P0.1 was increased from 1.1 +/- 0.2 (SEM) to 1.3 cm H2O +/- 0.3 (SEM), which was not significant. Comparing bronchospasm after saline to that after xylocaine we observed an increase in Ti afer xylocaine, which was correlated with the decrease in P0.1, suggesting that both were affected by airway anesthesia. We concluded that vagal airway receptors contribute to the increase in inspiratory drive which accompanies acute bronchospasm and also may contribute to the regulation of resting breathing pattern during bronchospasm in humans.