The ventilatory response to carbon dioxide in hyperoxic exercise

The sensitivity of the ventilatory response to carbon dioxide in hyperoxia during light (25 W) exercise was compared to that at rest in 14 volunteers. The method used was that of rebreathing. Two factors were found to produce artefactual changes in the slope of the response during exercise. First, breath-by-breath response lines showed that the maximum limit of ventilation was reached in 3 volunteers before the end of rebreathing, despite the low exercise load. The inclusion of such breaths in the calculation of the slope of the response could produce an artefactual decrease in slope. Second, most of the response lines showed an increase in their slope during exercise. However, a model of rebreathing in exercise showed that an increase in sensitivity could be the result of variation in the difference between end-tidal and central chemoreceptor carbon dioxide levels during exercise. A criterion derived from the model, proportional to the variation in this difference, was found to be correlated with the increase in sensitivity from rest to exercise. It was therefore concluded that the sensitivity of the ventilatory response to carbon dioxide during light exercise is unchanged from that at rest.     

Effect of perinatal hypercapnia on the adult ventilatory response to carbon dioxide

Burrowing mammals show a reduced ventilatory response to CO2 and CO2 retention. We examined whether this reduced responsiveness could be due to modification of chemoreceptors by persistent hypercapnia during development. Mice and rats were exposed to 6.0% CO2 throughout gestation and/or weaning and then removed to normocapnic air for a minimum of 6 weeks. Mouse gas pocket O2 and CO2 tensions and hematocrits were analyzed and compared with normocapnically raised controls. The ventilatory and blood gas and pH response to CO2 were compared in chronically cannulated test and control rats. Hematocrits and gas pocket CO2 and O2 tensions of mice and rat ventilatory and arterial blood CO2 and O2 tensions and pH responses were not different in test and control groups. There appears to be little or no developmental affect of CO2 suggesting that the reduced CO2 response seen in burrowers is genetically determined.     

Acute respiratory failure and obesity with normal ventilatory response to carbon dioxide and absent hypoxic ventilatory drive

We measured hypoxic and hypercapnic ventilatory drive in a 64 year old woman with acute respiratory failure, congestive heart failure and obesity when she was in remission. She had a ventilatory response to carbon dioxide (CO₂) comparable to that in six obese women without hypoventilation but no ventilatory response to hypoxia or to vital capacity breaths of 15 per cent CO₂ in N₂- Following weight loss, her ventilatory response to CO₂ increased but hypoxic ventilatory drive remained absent. These findings indicate that attenuation of hypoxic ventilatory drive caused by loss of peripheral chemoreceptor function can be a predisposing factor in the development of acute respiratory failure associated with obesity.     

The transient ventilatory response to carbon dioxide at rest and in exercise in man

A new technique has been developed to measure the transient response to inhaled CO2 using 30 sec pulses at constant inflow. Multiple experiments are ensemble-averaged in order to define the resulting small signals. We measured the peak changes in ventilation (delta V') and in PCO2 (delta PCO2), taking the ratio (delta V'/delta PCO2) as an index of response. Six healthy volunteers performed experiments at rest, 50 W and 100 W exercise. Three runs, each containing three pulses, were performed at each workload and subsequently averaged. Analysis of variance showed no significant difference between successive pulses or among subjects. delta V' did not differ significantly with workload, but delta PCO2 was progressively smaller as workload increased, and hence the response, delta V'/delta PCO2, greater. The delay between the rise in PCO2 and the rise in ventilation was also progressively shorter as workload increased, being 16-18 sec at rest, 7-13 sec at 50 W, and 3-6 sec at 100 W. Our results suggest that there is increased sensitivity to CO2 in exercise, which may be due to progressive activation of the peripheral chemoreceptors as work load increases. The delay at rest is too long for the peripheral chemoreceptor. Therefore, with these small stimuli, the central chemoreceptor must account for the CO2 response at rest.     

Compact apparatus for measurement of ventilatory response to carbon dioxide in newborns and infants.

We developed a rebreathing system for measuring response to carbon dioxide (CO2) of newborns and infants for use at the bedside. The system based on Read's method is small, easy to operate, and includes a computer-controlled gas switching sequence, computerized calculation, and display functions. We measured the CO2 response in 11 infants with or without apnea, who were born at 26-33 weeks gestation and were 12 to 215 days old at the time of the study. Our results suggest that the presence of apnea in premature infants may correspond to a low CO2 response. The method was convenient for clinical use because it allowed an investigator to carry out bedside tests in only a few minutes. With our system we were able to assess respiratory center function in newborns and infants.     

The ventilatory recruitment threshold for carbon dioxide

We report our initial experience with a technique with which the chemoresponsiveness of the respiratory controller can be characterized in terms of an inspiratory on-switch threshold to CO2. After suppression of phasic respiratory muscle activity by mechanical ventilation, a CO2 recruitment threshold (PCO2RT) was defined as the lowest alveolar CO2 tension at which CO2 supplementation to inspired gas caused a reappearance of inspiratory efforts. Because PCO2RT can be determined in the absence of a mechanical load on the ventilatory pump, respiratory system mechanics and inspiratory muscle function should not influence the measurement itself. Thus, this technique may be helpful to study ventilatory requirements and load responses in critically ill patients with respiratory failure. We have shown that inspiratory muscle recruitment can be equally well-inferred from changes in the airway pressure and flow tracings during mechanical ventilation, from the pattern of chest wall displacement, and from the integrated diaphragm electromyogram. Within a subject, PCO2RT is a reproducible measurement that is not influenced by ventilator settings and end-expiratory lung volume, provided that phasic respiratory muscle has been suppressed prior to CO2 supplementation. Details of the methodology, the likely determinants of PCO2RT, and the clinical utility of this technique are discussed.     

Premorbid ventilatory response to hypercapnia is not related to resting arterial carbon dioxide tension in hamsters with elastase-induced emphysema

Marked variability in resting steady-state arterial PCO2 (PaCO2) values are observed among patients with chronic obstructive pulmonary disease (COPD), independent of severity of their obstructive airways defect. The reasons for the development of hypercapnia in some but not in the others remain unclear. One hypothesis states that the level of morbid resting PaCO2 may be related to the premorbid hypercapnic ventilatory response (HCVR); accordingly, subjects who were relatively insensitive to CO2 breathing (low responders) develop CO2 retention in the face of lung disease. The present study investigated this hypothesis in the hamster model of elastase-induced emphysema. After obtaining steady-state HCVR in 19 unanesthetized unrestrained hamsters, emphysema was induced by intratracheal instillation of pancreatic elastase. Forty-five days later, minute ventilation and PaCO2 measurements were done, and lung function tests were obtained. The slopes of HCVR and morbid PaCO2 values varied from -0.09 to 2.36 ml/min/mmHg inspired PCO2 and 48.7 to 63.1 mmHg, respectively. There were no significant correlations between morbid PaCO2 values and premorbid HCVR or lung function test abnormalities caused by emphysema. These animal model studies do not support the hypothesis that the level of PaCO2 in patients with COPD is related to their premorbid HCVR.     

Respiratory effects of cold air breathing in anesthetized cats

Respiratory effects of cold air breathing were studied in anesthetized cats. Two different protocols were used: the air temperature was either lowered in an isolated segment, constituted by the larynx and oropharynx or in lower airways, so that the cats inspired the cold air directly. Temperatures ranged between 37 and 8 degrees C (first protocol) or between 37 and 15 degrees C (second protocol). When the temperature fell below 15 degrees C in the upper segment, marked increase in lung resistance occurred, without any significant changes in ventilatory variables nor in diaphragmatic electrical activity. The section of superior laryngeal nerves abolished this bronchomotor effect. In present experimental circumstances, thermal changes measured in lower airways when cats breathed cold air were mainly located in the cervical trachea. An increase in lung resistance and weak but significant changes in the diaphragmatic electromyogram began when the inspired air temperature fell below 25 degrees C. A selective local block of conduction in small vagal fibres by procaine or section of vagus nerves suppressed all these effects. In all cases the cold-induced changes in lung mechanics began very early (less than 10 sec) but continued for few minutes after the physiological temperature range had been restored in airways. The present data strongly suggest that the bronchomotor response to cold air breathing is a reflex, mediated by afferent fibres in the superior laryngeal nerves and in the vagus nerves.     

The effect of almitrine on the steady-state ventilatory response to carbon dioxide at rest and during exercise in man

Almitrine has potential as a tool for testing the physiological role of the peripheral chemoreceptor. The effects of almitrine on CO2 chemosensitivity were studied at rest and during light exercise using a constant inflow technique that avoids the hyperoxia of rebreathing methods. The steady-state ventilatory response to CO2 was measured in two groups of six normal men before and 150 min after 100 mg oral almitrine bismesylate or placebo. One group was studied at rest, the other while pedalling at 50 W. The resting group showed a significant increase in CO2 response slope after almitrine when compared with placebo but there was no significant change in the response intercept. During exercise the individual results were very variable and after almitrine no significant change was seen in either the response slope or intercept. Control ventilation was not affected by almitrine in either group. Even in the absence of marked hyperoxia the effect of almitrine on CO2 sensitivity at rest in small. The lack of effect at 50 W is against any important role for the peripheral chemoreceptor during light exercise but other interpretations are possible.     

Ventilation and breathing patterns during hemodialysis-induced carbon dioxide unloading

Important CO2 unloading occurs during hemodialysis (HD) when acetate-buffered dialysate is used. This is accompanied by alveolar hypoventilation. To gain more insight into the mechanisms of this alveolar hypoventilation, breathing patterns were studied in 5 patients with end-stage renal failure during HD using acetate-buffered dialysate, which induces CO2 unloading, or bicarbonate without CO2 loss. Ventilation was continuously measured with calibrated respiratory inductance plethysmography using techniques of multiple linear regression analysis. At regular intervals, arterial blood gas was sampled and expired air was analyzed. Breathing patterns were analyzed for VE, VT, TI, TE, and VT/TI. All data were compared with the respective starting value and with the respective value in the other setup. A greater decrease in ventilation was seen during HD with an acetate-containing dialysate because of irregular breathing patterns that resulted in a prolongation of expiratory time. Important variations in tidal volumes, striking apnea periods, and occasional periodic breathing were observed. We suggest that these irregularities are due to CO2 unloading leading to the point where ventilation is totally mediated through the output of the peripheral chemoreceptors.     

Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen

In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.