M. D. Altose

Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction.

The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. The two groups of patients, however, showed different occlusion pressure responses to CO2 (deltaP100/deltaPCO2): deltaP100/deltaPCO2 was normal in the eucapnic patients but subnormal in the hypercapnic patients. Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients.

Comparison of occlusion pressure and ventilatory responses.

The airway pressure 100 msec after the onset of an inspiratory effort against a closed airway (P100, occlusion pressure) is theoretically a more accurate index of respiratory neuron motor output than ventilation. Occlusion pressure and ventilation responses to hypercapnia were compared in repeated trials in 10 normal subjects while in the seated and supine positions. During progressive hypercapnia changes in P100 were also compared to changes in tidal volume and inspiratory airflow. These studies show that occlusion pressure increases linearly with hypercapnia in both sitting and supine subjects. Changing from the seated to the supine position, or vice versa, had no significant effect on either ventilation or occlusion pressure responses to CO2. Correlations between P100 and ventilation or airflow rate were significantly higher than correlations between P100 and tidal volume or breathing frequency. Intermittent random airway occlusion had no effect on either ventilation or pattern of breathing during hypercapnia. Occlusion pressure responses were no less variable than ventilation responses in groups of subjects whether studied seated or supine. However, maintenance of a constant moderate breathing frequency (20 breaths per minute) reduced the interindividual variability in ventilation and occlusion pressure responses to hypercapnia.

Effect of fiberoptic bronchoscopy on respiratory performance in patients with chronic airways obstruction.

Lung volumes, airway resistance, expiratory flow rates, distribution of ventilation, and arterial blood gases were measured before and after fiberoptic bronchoscopy in 13 patients with moderately severe chronic airways obstruction and in 10 healthy non-smoking controls. Arterial blood gases were also monitored serially during the procedure. Arterial oxygen tension (Pao2) fell during fiberoptic bronchoscopy in both patients and controls whereas arterial carbon dioxide tension and pH remained unchanged. Control subjects had no change in lung mechanics after fiberoptic bronchoscopy. However, the patients consistently developed increased airway obstruction after fiberoptic bronchoscopy. Within 24 hours after bronchoscopy lung function in the patients returned to baseline values, except for the residual volume which remained abnormally high. The topical application of lignocaine (Lidocaine) for local anesthesia before fiberoptic bronchoscopy produced no effect on lung mechanics in nine patients and 10 controls, but Pao2 decreased in both the patient and control groups. These results indicate that fiberoptic bronchoscopy consistently inpairs lung mechanics and gas exchange in patients with chronic airways obstruction but that the impairment is mild and reversible. Lignocaine administration as well as the intubation procedure contribute to the fall in Pao2 which occurs both in the patients and in subjects without pre-existing lung disease.

Airway occlusion pressures in awake and anesthetized goats.

The pressures generated by the inspiratory muscles as they contract isometrically during airway occlusion seem to be a measure of respiratory neuron efferent activity. The ventilatory and occlusion pressure responses to increasing levels of CO2 were studied in goats, awake and anesthetized, with and without inspiratory flow resistance. Hypercapnia was produced by rebreathing. Randomly, during rebreathing, inspiratory airflow was prevented on single breaths. Ventilation and pressures developed during the first 100, 200, 300 and 400 milliseconds of an inspiratory effort against a complete occlusion increased linearly with CO2 in both awake and anesthetized animals. Anesthesia reduced both the ventilatory and occlusion pressure responses to CO2. Inspiratory resistance increased occlusion pressure responses in awake goats but not in the same animals when anesthetized. Inspiratory airflow resistance seems to augment respiratory efferent activity as reflected in the pressure responses only in conscious goats. Thus the response to an inspiratory resistance seems to depend on the state of consciousness.

Respiratory responses to changes in airflow resistance in conscious man

The time course and magnitude of adjustments in respiratory activity during the application and following the removal of inspiratory resistive loads were determined in conscious men. Changes in airflow resistance were made periodically during rebreathing of a gas mixture of carbon dioxide and oxygen. Ventilation, the ratio of tidal volume to inspiratory duration and the mouth pressure during airway occlusion, 100 ms after the onset of inspiration were used as measures of inspiratory neuromuscular activity. The occlusion pressure was measured during each breath using an electrically activated solenoid shutter which obstructed the airway for only the first 100 ms of each inspiration. During the second breath following the application of the resistive load, there was an increase in inspiratory output which occurred independently of changes in PCO2 and PO2. Further increases in inspiratory activity during successive loaded breaths, however, were due exclusively to changing chemical drive. The level of inspiratory neuromuscular activity remained elevated for a single breath following removal of the added resistance. Adjustments in respiratory activity were greater the more severe the load. The results suggest that non-chemically mediated respiratory compensation in conscious individuals develops rapidly and is important in maintaining ventilation when breathing is encumbered.

The Interaction of FRC and Ventilation on Occlusion Pressure in Conscious Man

Analytical and experimental results relating the interaction of functional residual capacity (FRC) and ventilation (V) on occlusion pressure in conscious man are presented. An analytical model was developed relating the airway pressure measured 100 ms after occlusion (P100) with FRC and V just before occlusion. By relating the change in diaphragmatic force with time during breathing to that during occlusion, it was found that P100 and IFRC could be linearly related. In order to test this model, 16 normal adult subjects with different FRC values (2.0 to 5.6 1) were studied during periods of increasing ventilation. Subjects increased V by rebreathing a mixture of 7% CO2 and 93% 02. Neither AP100/APC02 nor AV/APCO2 could be correlated to FRC since the differences in motoneuron activity in response to hypercapnia were probably greater than the variations in FRC. Linear regression analysis on all 16 subjects demonstrated a significant effect of FRC on the relationships P100 versus V, and AP100/APCO2 versus A V/APCO2. These experimental findings were in close agreement with analytical predictions and suggest that subjects with larger FRC values have a greater ventilation and ventilatory response for the same occlusion pressure and occlusion pressure response, respectively.