End-tidal CO2 response to low levels of inspired CO2 in awake beagle dogs

The steady-state end-tidal CO2 tension (PCO2) was examined during control and 1% CO2 inhalation periods in awake beagle dogs with an intact airway breathing through a low dead-space respiratory mask. A total of eight experiments were performed in four dogs, comprising 31 control observations and 23 CO2 inhalation observations. The 1% inhaled CO2 produced a significant increase in the steady-state end-tidal PCO2 comparable to the expected 1 Torr predicted from conventional CO2 control of ventilation. We conclude that 1% inhaled CO2 results in a hypercapnia. Any protocol that is to resolve the question of whether mechanisms are acting during low levels of inhaled CO2 such that ventilation increases without any change in arterial PCO2 must have sufficient resolving power to discriminate changes in gas tension in magnitude predicted from conventional (i.e., arterial PCO2) control of ventilation.     

DIDS decreases CSF HCO3- and increases breathing in response to CO2 in awake rabbits

An inhibitor of the HCO3-/Cl- exchange carrier protein, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) or vehicle was infused in mock cerebrospinal fluid (CSF) via the cisterna magna in conscious rabbits at 10 mumol/l for 40 min at 10 microliter/min. Neither treatment had any effect over 2-5 h on the non-CO2-stimulated CSF ion values or blood gases. With CO2 stimulation such that arterial PCO2 (PaCO2) was increased 25 Torr over 3 h, DIDS treatment significantly decreased the stoichiometrically opposite changes in CSF [HCO3-] and [Cl-] that normally accompany hypercapnia and reflect ionic mechanisms of CSF pH regulation. Expressed as delta CSF [HCO3-]/delta PaCO2, DIDS treatment decreased the CSF ionic response by 35%. In a separate paired study design DIDS administration via the same protocol had no effect on resting ventilation but significantly increased the ventilation and tidal volume responses to a 28-Torr increase in PaCO2. Expressed as change in minute ventilation divided by delta PaCO2, DIDS treatment produced a 39.6% increase. The results support the concept of a DIDS-inhibitable anion exchange carrier being involved in CSF pH regulation in hypercapnia and suggest a DIDS-related effect on the ventilatory response to CO2.     

Respiratory responses to intravenous and intrapulmonary CO2 in awake dogs

Ventilatory responses to CO2 inhalation and CO2 infusion were compared in the awake dog. The CO2 was introduced directly into the systemic venous blood via a membrane gas exchanger in a femoral arteriovenous shunt circuit, and the extracorporeal blood flow, QX, was maintained constant at one of two rates: low, 0.5 l/min; or high, 2.0 l/min. A total of 13 experiments was performed in four dogs comprising 50 control and 25 inhalation and infusion observations at each of the two flow rates. Comparison of CO2-response curve slopes, S = delta V E/delta PaCO2, between CO2 inhalation and infusion showed no significant difference either within or between flow rates. The mean value of S for all conditions was 1.88 l/min per Torr with a 95% confidence interval of 1.66 -2.14. An independent additive ventilatory drive amounting to 28% of low-flow control VE was found at the highflow rate. We conclude that at constant blood flow the responses to both CO2 inhalation and infusion are hypercapnic and not significantly different.     

Effect of upper airway CO2 on breathing in awake ponies

We determined whether the [CO2] in the upper airways (UA) can influence breathing in ponies and whether UA [CO2] contributes to the attenuation of a thermal tachypnea during periods of elevated inspired CO2. Six ponies were studied 1 mo after chronic tracheostomies were created. For one protocol the ponies were breathing room air through a cuffed endotracheal tube. Another smaller tube was placed in the tracheostomy and directed up the airway. By use of this tube, a pump, and prepared gas mixtures, UA [CO2] was altered without affecting alveolar or arterial PCO2. When the ponies were at a neutral environmental temperature (TA) and breathing frequency (f) was 8 breaths X min-1, increasing UA [CO2] up to 18-20% had no effect on f. However, when TA was increased 20 degrees C to increase f to 50 breaths X min-1, then increasing UA [CO2] to 6% or to 18-20% reduced f by 5 +/- 1.7 (SE) and 12 +/- 1.6 breaths X min-1, respectively (t = 3.3, P less than 0.01). These data suggest that in the pony there exists a UA CO2-H+ sensory mechanism. For a second protocol the ponies were breathing a 6% CO2 gas mixture for 15 min in the normal fashion over the entire airway (nares breathing, NBr) or they were breathing this gas mixture for 15 min through the cuffed endotracheal tube (TBr). At a neutral TA, increasing inspired [CO2] to 6% resulted in a 6-breaths X min-1 increase in f during both NBr and TBr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of VCO2 in control of breathing of awake exercising dogs

Steady-state ventilatory responses to CO2 inhalation, intravenous CO2 loading (loading), and intravenous CO2 unloading (unloading) were measured in chronic awake dogs while they exercised on an air-conditioned treadmill at 3 mph and 0% grade. End-tidal PO2 was maintained at control levels by manipulation of inspired gas. Responses obtained in three dogs demonstrated that the response to CO2 loading [average increase in CO2 output (Vco2) of 216 ml/min or 35%] was a hypercapnic hyperpnea in every instance. Also, the response to CO2 unloading [average decrease in Vco2 of 90 ml/min or 15% decrease] was a hypocapnic hypopnea in every case. Also, the analysis of the data by directional statistics indicates that there was no difference in the slopes of the responses (change in expiratory ventilation divided by change in arterial Pco2) for loading, unloading, and inhalation. These results indicate that the increased CO2 flow to the lung that occurs in exercise does not provide a direct signal to the respiratory controller that accounts for the exercise hyperpnea. Therefore, other mechanisms must be important in the regulation of ventilation during exercise.     

Ventilation and acid-base balance in awake dogs exposed to heat and CO2

Some awake quiet dogs pant at cool ambient temperature (Ta) and some do not pant even when acutely exposed to heat. The purpose of the study was to determine whether this puzzling variability in respiratory behavior diminished during prolonged heat. The contributions of thermal and CO2 drives to respiratory adaptations were also examined. Five awake dogs acclimated to 20 degrees C were studied before and 2 and 48 h following exposure to 30-31 degrees C. Rectal temperature did not change; the important thermal stimulus, even at 48 h, appeared to be the increase in peripheral temperature. Variability between nonpanting and panting persisted over 48 h. On the average, ventilation (VE) doubled during heat, largely due to increased dead space ventilation. Nonpanting dogs at cool Ta decreased the threshold of the ventilatory response to CO2. A panting dog at cool Ta changed its slope of the ventilatory response from negative to positive. During hypercapnia in acute heat, ventilatory pattern changed so that frequency increased and tidal volume decreased for a given VE. By 48 h of heat, the ventilatory response to CO2 returned to control in only two dogs, but the ventilatory pattern during hypercapnia returned to control in four dogs. Since thermal stimuli remained unchanged at 48 h, adaptations of respiratory control may have been related to progressive adjustments of strong ions and acid-base balance.     

Ventilatory response to exercise in subjects breathing CO2 or HeO2

Babb, T. G. Ventilatory response to exercise insubjects breathing CO₂ orHeO₂.J. Appl. Physiol. 82(3): 746-754, 1997.To investigate the effects of mechanical ventilatory limitationon the ventilatory response to exercise, eight older subjects with normal lung function were studied. Each subject performed graded cycleergometry to exhaustion once while breathing room air; once whilebreathing 3% CO₂-21%O₂-balanceN₂; and once while breathing HeO₂ (79% He and 21%O₂). Minute ventilation(E) and respiratory mechanics weremeasured continuously during each 1-min increment in work rate (10 or20 W). Data were analyzed at rest, at ventilatory threshold (VTh),and at maximal exercise. When the subjects were breathing 3%CO₂, there was an increase(P < 0.001) inE at rest and at VTh but not duringmaximal exercise. When the subjects were breathingHeO₂,E was increased(P < 0.05) only during maximalexercise (24 ± 11%). The ventilatory response to exercise belowVTh was greater only when the subjects were breathing 3% CO₂(P < 0.05). Above VTh, theventilatory response when the subjects were breathingHeO₂ was greater than whenbreathing 3% CO₂(P < 0.01). Flow limitation, aspercent of tidal volume, during maximal exercise was greater(P < 0.01) when the subjects werebreathing CO₂ (22 ± 12%) thanwhen breathing room air (12 ± 9%) or when breathingHeO₂ (10 ± 7%)(n = 7). End-expiratory lung volumeduring maximal exercise was lower when the subjects were breathingHeO₂ than when breathing room airor when breathing CO₂(P < 0.01). These data indicate thatolder subjects have little reserve for accommodating an increase inventilatory demand and suggest that mechanical ventilatory constraintsinfluence both the magnitude of Eduring maximal exercise and the regulation ofE and respiratory mechanics duringheavy-to-maximal exercise.