Alveolar PCO2 Research Articles

Arterial P CO2 and lung ventilation in man exposed to 1-5% CO2 in the inspired gas.

Conflicting results have been published on the shape of the curve relating the change in lung ventilation to the change in alveolar or arterial PCO2 induced by increased inspired CO2 (the CO2 sensitivity). In this study eight human subjects with in-dwelling arterial cannulae were each exposed to five different levels of increased inspired CO2 (1-5%). Arterial PCO2 and ventilation were measured in the 7th minute of each period of CO2 exposure. Each CO2 exposure period was flanked by control periods in which similar measurements were carried out during air breathing. We found non-linear increases in both ventilation and arterial PCO2 with increasing levels of inspired CO2. When 5% CO2 in air was inspired the arterial PCO2 increased by about 15% of the inspired CO2 load. There was no significant non-linearity in the relation between change in alveolar ventilation (normalized to body surface) and change in arterial PCO2. The inter-individual variation in CO2 sensitivity was less when alveolar ventilation was normalized to the CO2 output rather than to body surface area. We conclude that the sensitivity to CO2 is close to constant within the range 0-5% CO2 in the inspired gas.

CO2 sensitivity in humans breathing 1 or 2% CO2 in air.

Ventilation increases when the concentration of CO2 in the inspired gas is increased, thereby limiting the increase in alveolar and arterial PCO2. The extent of this compensation at low levels of inspired CO2 has been debated. In five healthy humans, we have measured arterial PCO2, arterial pH and ventilation during exposure to 1 and 2% CO2 in the inspired gas. Each exposure lasted at least 7 min and arterial blood was sampled over at least 30 s during the last minute of each period. The ventilation was measured in the sixth and seventh min. The protocol included the sequences: control-test-control and test-control-test with 'test' representing CO2 loading and 'control' 0% CO2, respectively. We found that arterial PCO2 increased and pH decreased at both levels of inspired CO2. The mean increase in arterial PCO2 was 0.09 and 0.25 kPa, at CO2 1 and 2%, respectively. Three subjects were exposed to 1% CO2 in the inspired gas for 28 min flanked by similar control periods. In each period arterial blood samples were taken at 2- or 3-min intervals. Arterial PCO2 remained elevated for at least 20 min during the CO2 loading. The sensitivity to CO2 (ratio of increase in ventilation to increase in arterial PCO2) was within the range described by others at higher levels of inspired CO2. Arterial PCO2 increased by about 10% of the imposed load. We conclude that the increase in ventilation provides only incomplete compensation for exposure to CO2: arterial CO2 is increased and arterial pH decreased also at very low levels of inspired CO2.

Theoretical analyses for arterial-venous O2 content difference and haldane effect during rebreathing.

The Haldane effect coefficient in vivo and arterial-venous O2 content difference [a-v)Co2) are, more or less, influenced by the contact time (tc), PO2 and PCO2 differences between venous blood and alveolar air. To increase the accuracy of the (a-v)CO2 and the cardiac output measured by means of the rebreathing technique, factors to correct the Haldane effect (F(H] and (a-v)CO2 (F(avCO2] were obtained theoretically from the numerical solutions of simultaneous O2 and CO2 diffusions in the red blood cell. Both the factors were complicated functions of tc, the difference in PCO2 between venous blood and alveolar air, as well as (a-V)CO2. For simplicity, we eliminated tc from the above functions by using the standardized relation between the tc and (a-v)CO2 measured from a rebreathing experiment in man. The F(H) was a linear function of (a-v)CO2. The (a-v)CO2 was calculated by dividing the product of F(H) and the slope of the CO2 dissociation curve by that of a gas exchange ratio against the PCO2 in rebreathing air. The F(avCO2) was given by a ratio of (a-v)CO2 at any alveolar PCO2 to the standard one, in which arterial blood has the same intracellular pH as that in venous blood. It was a linear function of the difference in PCO2 between venous blood and alveolar air, whose slope was inversely related to the (a-v)CO2 itself.

The Effect of Naproxen on Acute Mountain Sickness and Vascular Responses to Hypoxia

The role of prostaglandins in the pathogenesis of acute mountain sickness and two hypoxia-induced vascular responses was evaluated using the cyclooxygenase inhibitor naproxen. Eleven men spent 24 hours at sea level, followed by 34 hours of decompression to 428 mm Hg while receiving naproxen (N), 250 mg twice daily or placebo (P) in a double-blind crossover trial. Serum naproxen levels measured by high pressure liquid chromatography were not changed by hypoxia. The severity of acute mountain sickness (AMS) by the Environmental Symptom Questionnaire scores and observer assessment were unaffected by drug treatment. Retinal artery diameter measured from projected fundus photographs was increased after 27 hours at altitude (11.4 +/- .5 mm) vs. sea level (9.4 +/- .5 mm, p less than 0.05) during both trials. Upright mean arterial pressure fell after 6 hours at altitude (79 +/- 3 mm Hg during N and P vs. 92 +/- 3 at sea level, p less than 0.01). Minute ventilation, end expiratory alveolar PO2 and PCO2 did not differ between drug trials. This study suggests vasodilating prostaglandins do not have a major role in the genesis of AMS, hypoxia-induced retinal vasodilatation, or postural blood pressure responses in man.

Patterns of breathing in response to alternating patterns of alveolar carbon dioxide pressures in man.

The time profile of alveolar PCO2 within the respiratory cycle has been forced to follow contrasting patterns in alternate breaths, in two different ways. Within-breath changes (w.b.c., with a CO2-rich inspirate supplied early or late in alternate inspirations) involved minimal alternation of end-tidal PCO2. Between-breath changes (b.b.c., with whole inspirates of CO2-free or CO2-rich gas) involved large swings of end-tidal PCO2. As previously reported (Metias, Cunningham, Howson, Petersen & Wolff, 1981), both patterns of forcing were associated with alternation of ventilation, but only when hypoxia was present. The patterns of the alternating reflex responses in 118 runs on four human subjects in steady hypoxia are described in terms of alternation of inspiratory and expiratory tidal volume, time and mean flow. These patterns often disappeared, or changed unpredictably in mid-run. The inspiratory pattern of reflex alternation depended in part on the type of forcing, but alternation of inspiratory tidal volume was usually observed with both types. No single pattern of expiratory alternation emerged as predominant. The pattern of reflex expiratory alternation was surprisingly independent of the pattern of inspiratory alternation: indeed, in w.b.c., but not in b.b.c., alternation of mean expiratory flow and of mean inspiratory flow were mutually exclusive. It is concluded that in man, as in cats and dogs, the arterial chemoreceptor pathway has access to various parts of the respiratory pattern generator, the exact response depending to some extent on the timing within the respiratory cycle. In particular, expiratory variables may be influenced directly through the arterial chemoreceptor pathway, i.e. without any supposedly mediating inspiratory alternation being demonstrable. The results are discussed briefly in relation to some current views on the organization of respiratory control.

Ventilatory sensitivity to inhaled carbon dioxide around the control point during exercise.

Rapid steady-state CO2 responses were determined in five normal adults at rest and at up to six levels of exercise by injecting pure CO2 at a constant flow into the inspiratory limb of a breathing circuit. Ventilation (V) was measured with a dry gas meter and PCO2 at the mouth was recorded by a mass spectrometer. Mean alveolar PCO2 (PACO2) was taken as equal to end-tidal PCO2 at rest, and during exercise was derived graphically from the sloping alveolar plateaus. The accuracy of the latter method was checked in separate experiments against arterial PCO2 (PaCO2). The mean results showed a linear relationship between change in PACO2 and change in V for work loads ranging from rest to 75 W (r = 0.94-0.98). Above 75 W the response became concave down with an initial essentially isocapnic phase. This suggests that during exercise there is a large increase in CO2 sensitivity about the control point.

Role of hypocapnia in the alveolar surfactant increase induced by free fatty acid intravenous infusion in the rabbit.

Intravenous infusion of free fatty acid (FFA) produces an increase in the alveolar surfactant pool of the rabbit and pulmonary edema, hyperventilation, hypoxemia and hypocapnia. Previous studies suggested that alveolar PCO2 would be a regulator of intracellular storages of surfactant. In order to study the role of hypocapnia in the increase of lung surfactant in our experiments we administered 20 mg FFA X kg-1 X min-1 i.v. to rabbits breathing room air (n = 10) or 5% CO2, 21% O2, 74% N2 (n = 7). Disaturated phosphatidylcholine (DSPC) was determined in bronchial-alveolar lavage fluid as index of alveolar surfactant content, 5% CO2 in the inspired air prevented the hypocapnia and blocked the increase in DSPC induced by FFA (p less than 0.01). Pulmonary edema post-FFA was not changed by 5% CO2 administration. We conclude that hypocapnia produced by hyperventilation during FFA infusion would be an important factor in the increase of DSPC observed after FFA infusion.

Relation between the contact time and venous and alveolar PCO2 at rest.

The simultaneous partial differential equations for diffusions of O2, CO2, and HCO 3 − ions in the red blood cell (RBC) were solved numerically, taking chemical reactions of Bohr- and Haldane-effects into account. The diffusion equations and the chemical reactions were computed alternatively in an increment time of 2 msec. After solving each of the three diffusion equations, the Po2, O2 saturation (S), Pco2, pH and HCO 3 − content were corrected by using the equations of Bohr- and Haldane-effects, and a modified Henderson-Hasselbalch equation (Kagawa and Mochizuki, 1984). The Bohr-shift was calculated from Hill’s equation by assuming its K value to be a function of the intracellular pH. The change in intracellular Pco2 due to the Haldane effect was also evaluated by means of the modified Henderson-Hasselbalch equation, in which the buffer value was taken as 44 mmol · 1(RBC)−1 · pH c −1 . The computed Pco2 profiles during the Haldane effect in a closed vessel was compatible wit the experimental data of Klocke (1973). The extracellular Po2 profile computed during the Bohr-off-shift in a closed system coincided well with the experimental data of Nakamura and Staub (1964) and Forster and Steen (1968).

Ventilatory drive during face immersion in man.

Four series of experiments have been performed in normal subjects to determine whether face immersion gives rise to a reduction in ventilatory drive. Such a response might be advantageous, like the cardiovascular components of the 'diving response', in prolonging breath-hold diving. In the first series, ventilatory drive was measured indirectly as the maximal voluntary breath-holding time, starting each breath-hold at the same alveolar partial pressures and at the same lung volume. When the face was immersed in cold water, breath-holding times were increased by 14%. The breaking point occurred at a higher alveolar PCO2 and the rate of rise of PCO2 was not affected. Control immersions in warm water had no effect. In the second and third series, subjects lay prone and breathed either air or 5% CO2 through a valve in the bottom of a bowl. Minute ventilation was measured before, during and after 5 min of face immersion in cold water. Transient hypoventilations of 13% and 10% respectively were seen, accompanied by small rises in alveolar PCO2. In control experiments, immersion of the forearm in cold water produced the opposite responses. In the fourth series, a cold wet pack was applied to the face during moderate steady-state exercise. A small irregular hypoventilation was seen, but not in control experiments when a warm pack was applied. Face temperatures fell by about 10 degrees C in these experiments. No material changes were found in the temperatures of the inspired air or of the aural canal. It is concluded that face immersion in cold water causes a modest reduction in ventilatory drive in man. This appears to be a component of the 'diving response'.

Evaluation of uneven distribution of VA/Q ratio from data on exchange of respiratory gases.

A new approach has been developed for evaluating uneven distribution of ventilation/perfusion ratio, VA/Q, based on a two-compartment model with a reciprocal VA/Q relation. The VA/Q ratios were expressed by mu . (1-rho)/rho and mu . rho/(1-rho), where mu and rho were referred to as the "ideal" VA/Q ratio and unevenness factor, respectively. During steady state breathing, arterial blood was analyzed for PO2 and PCO2, and end-tidal PCO2 as well as the gas exchange ratio, R, was measured. After steady state breathing a rebreathing experiment was performed, and the arterial-venous O2 content difference, (a-v)CO2, was measured, and then, multiplying it by R, the venous-arterial CO2 content difference, (v-a)CCO2, was obtained. Referring to these values the mixed venous PO2 and PCO2 were estimated from arterial PO2 and PCO2, using the O2 and CO2 dissociation curves. The VA/Q line and iso-R line were drawn to find mu, and further, total arterial, and alveolar PO2 and PCO2 of the two-compartment model were computed by changing both rho and the mixing weight factor, phi. The phi value was determined so as to make the above PO2-PCO2-locus pass through the measured arterial PO2 and PCO2. The rho value was selected so that the computed alveolar PCO2 fitted to the end-tidal one. The experiments were performed on 8 normal subjects in normoxia and hyperoxia with PIO2 245 Torr. The mean phi values in normoxia and hyperoxia were 0.50 and 0.56, respectively. The mean rho values in normoxia and hyperoxia were 0.438 and 0.428, respectively. The VA/Q ratio was decreased in hyperoxia because of a decrease in VA value.

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.

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)

The Ventilatory Response to CO2 is Not Linear within The Normal Range of Alveolar PCO2

The Ventilatory Response to CO2 is Not Linear within The Normal Range of Alveolar PCO2

Respiratory effects of carbon dioxide-induced changes of medullary extracellular fluid pH in cats.

Acute and steady-state responses to hypercapnia of respiratory output, measured as integrated phrenic nerve activity, and medullary extracellular fluid (e.c.f.) pH, measured directly, were determined in paralysed, vagotomized and glomectomized cats. Medullary e.c.f. pH responds within seconds to an acute change of alveolar and arterial PCO2. The respiratory response closely and inversely matches the e.c.f. pH change, but not the cerebrospinal fluid pH change. The medullary e.c.f. pH change following a rapid step-change in end-tidal PCO2 requires at least 5 min for a new steady state to be achieved. Steady-state studies in twenty-six cats show: (a) that the respiratory response to progressive hypercapnic stimulation of the central chemoreceptors is curvilinear (Eldridge, Gill-Kumar & Millhorn, 1981), (b) that the relationship between increasing end-tidal PCO2 and medullary hydrogen ion concentration [(H+]) or changes of pH is linear (r = 0.995); a doubling of PCO2 causes 0.260 units pH change, (c) there is a curvilinear relationship between e.c.f. [H+] and the respiratory response that is the same as that found with CO2. We conclude that medullary e.c.f. pH measured by means of a surface electrode accurately reflects the CO2-induced [H+] stimulus to respiration. The decreasing respiratory responses to identical changes of central chemoreceptor input are due to progressive neuronal saturation of a central pathway between the chemoreceptors and the respiratory controller.

Rate of change of alveolar carbon dioxide and the control of ventilation during exercise.

The relationship between rate of change of alveolar PCO2 (delta PA, CO2/delta te), CO2 output (VCO2) and ventilation (VE) has been determined following a rapid increase in exercise intensity, to test the hypothesis that VE is related to VCO2 by a feed-forward control system responding to delta PA, CO2/delta te. There was a close relationship between delta PA, CO2/delta te and VCO2 (delta PA, CO2/delta te = 3.2 VCO2 + 0.85), but delta PA, CO2/delta te increased more rapidly than VCO2. Increases in mean inspiratory flow, an index of inspiratory drive, were more closely related to changes in delta PA, CO2/delta te than to changes in VCO2. Increases in VE during transient and steady-state conditions may be described by the equation: VE = 6.76 delta PA, CO2/delta te -3.50, a relationship which is consistent with a feed-forward control system.

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction.

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.

Airway deadspace, end-tidal CO2, and Christian Bohr.

In order to calculate alveolar deadspace, an important measure of ventilation/perfusion mismatching, it is necessary to measure airway or anatomical deadspace (VDaw) and physiological deadspace. VDaw is usually measured graphically or by similar means, but sometimes it is estimated from a formula, based on Christian Bohr's work, in which end-tidal PCO2 is used as a measure of alveolar PCO2. In 58 patients undergoing anaesthesia and positive pressure ventilation, there were large errors in this estimate of VDaw compared to a graphical method. At tidal volumes of 400-500 ml, the median error was 34 ml; at larger tidal volumes, the median error increased to 74 ml (P less than 0.001). The size of the error was correlated to the slope of phase III, the part of the CO2 tracing representing alveolar CO2, at both ventilator settings (P less than 0.01). It is concluded that estimates of VDaw based on end-tidal PCO2 are unreliable, and their use will lead to a large part of the alveolar deadspace being wrongly accredited to VDaw.

Apnea of Prematurity: I. Lung Function and Regulation of Breathing

It has been suggested that apnea of prematurity may be caused by "immaturity" of central control of breathing. To test the validity of this hypothesis tidal volume (VT), alveolar ventilation (VA), alveolar Pco2 (Paco2), esophageal pressure change, and the slope of the CO2 response curve (delta Ve [minute ventilation]/delta Paco2) were determined in 18 infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 healthy newborns used as control subjects. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The results were as follows: Vt (4.4 +/- 1.0 mL/kg v 5.3 +/- 1.6 mL/kg), Va (96 +/- 21 mL/kg/min v 129 +/- 33 mL/kg/min), Paco2 (45.4 +/- 8.5 mm Hg v 35.6 +/- 4.7 mm Hg), esophageal pressure change (4.5 +/- 0.9 cm H2O v 6.0 +/- 1.8 cm H2O), delta Ve/delta Paco2 (20.2 +/- 10.6 mL/min/kg/mm Hg CO2 v 40.7 +/- 19.9 mL/min/kg/mm Hg CO2). There was a significant difference between infants with and without apnea for all measurements. The results indicate a decreased respiratory center output and a depressed ventilatory response to CO2 in infants with apnea. As there was no difference between the two groups in pulmonary mechanics or oxygenation, the findings support the hypothesis that a central disturbance in regulation of breathing is the cause of apnea in these infants.

Ventilatory response to hypercapnia during sleep and wakefulness in cats.

Eucapnic breathing and ventilatory responses to hypercapnia were studied in seven cats during sleep and wakefulness. No significant differences were found in minute ventilation (VE), alveolar ventilation (VA), or alveolar PCO2 (PACO2) between wakefulness (W) and non-rapid-eye-movement (NREM) sleep, but VA and VE were less during rapid-eye-movement (REM) sleep than W, and PACO2 declined during REM compared with NREM. To test the hypercapnic response, cats were required to rebreathe from a bag containing 6% CO2 and 94% O2 (to eliminate the hypoxic response). The response curve was displaced to the right during NREM and REM; the slope was reduced only during REM to a value about 75% of W and NREM. Eye movements, quantifying phasic REM, were only slightly correlated (negatively) with the deviation of ventilation from the response curve. The hypercapnic response was diminished, not eliminated, during REM, even during phasic REM. The reduced slope arose principally from the failure of the expiratory time to shorten with hypercapnia as during W and NREM. The cat's hypercapnic response compared with the dog's, measured by others with the same methodology, suggests that differences between species may be more crucial than methodology in explaining earlier contradictory results.

Gas-blood Pco2 and Po2 equilibration in a steady-state rebreathing dog preparation.

Alveolar gas and mixed venous blood PCO2 and PO2 were compared in a steady-state rebreathing dog preparation, during spontaneous breathing and mechanical ventilation, by a new null-balancing method that removes potential biases in the comparison of measurements in the blood and gas phases and includes an inert gas test to verify the equilibration between the rebreathing lung and the bag. No systematic PCO2 and PO2 differences were observed under equilibrium conditions. However, inert gas studies suggested that a high percentage of measurements obtained during spontaneous breathing were unreliable because of inadequate equilibration between blood and rebreathing bag (attributable to reduced ventilation or perfusion) and that all mechanical ventilation measurements were acceptable. The present data support the view that no PCO2 or PO2 gradients exist when the pulmonary capillary blood and alveolar gas are in equilibrium; the data also suggest that the steady-state rebreathing dog preparation may not be completely stable and that the time course of PCO2 and PO2 in the rebreathing bag may not be reliable as a means of assessing the equilibration between blood and bag.