Effects of airway anesthesia on ventilatory responses to graded dead spaces and CO2

Ventilatory response to graded external dead space (0.5, 1.0, 2.0, and 2.5 liters) with hyperoxia and CO2 steady-state inhalation (3, 5, 7, and 8% CO2 in O2) was studied before and after 4% lidocaine aerosol inhalation in nine healthy males. The mean ventilatory response (delta VE/delta PETCO2, where VE is minute ventilation and PETCO2 is end-tidal PCO2) to graded dead space before airway anesthesia was 10.2 +/- 4.6 (SD) l.min-1.Torr-1, which was significantly greater than the steady-state CO2 response (1.4 +/- 0.6 l.min-1.Torr-1, P less than 0.001). Dead-space loading produced greater oscillation in airway PCO2 than did CO2 gas loading. After airway anesthesia, ventilatory response to graded dead space decreased significantly, to 2.1 +/- 0.6 l.min-1.Torr-1 (P less than 0.01) but was still greater than that to CO2. The response to CO2 did not significantly differ (1.3 +/- 0.5 l.min-1.Torr-1). Tidal volume, mean inspiratory flow, respiratory frequency, inspiratory time, and expiratory time during dead-space breathing were also depressed after airway anesthesia, particularly during large dead-space loading. On the other hand, during CO2 inhalation, these respiratory variables did not significantly differ before and after airway anesthesia. These results suggest that in conscious humans vagal airway receptors play a role in the ventilatory response to graded dead space and control of the breathing pattern during dead-space loading by detecting the oscillation in airway PCO2. These receptors do not appear to contribute to the ventilatory response to inhaled CO2.     

Transient ventilatory response to CO2 as a function of sleep state in full-term infants

The influence of sleep state on the transient (i.e., initial 60 s) and steady-state ventilatory responses to 2% CO2 inhalation was studied in 19 healthy full-term infants. A nasal mask pneumotachometer was used to measure ventilation and end-tidal CO2 partial pressure (PCO2) and enabled abrupt changes in the inspired gas concentration to be made. The magnitude of the change in minute ventilation for both the transient and steady-state responses to CO2 was not statistically different between active (AS) and quiet (QS) sleep. Nonetheless the greater variability in minute ventilation during AS compared with QS continued throughout the period of CO2 inhalation and was associated with a more variable change in ventilation in the individual infants during AS. There was a greater increase in end-tidal PCO2 over the first 60 s during AS (3.3 +/- 0.3 vs. 2.6 +/- 0.2 Torr, in AS and QS, respectively, P less than 0.03). This may indicate a smaller initial increase in alveolar ventilation, relative to CO2 delivery to the lungs, in response to CO2 inhalation during AS. Asynchronous chest wall movements were more common during AS than QS (P less than 0.005) and did not change with CO2. The inconsistent transient ventilatory response to CO2 during AS compared with QS may be important in the behavior of infants to spontaneous episodes of hypercapnia occurring during AS.     

Effect of plasma carbonic anhydrase on ventilation in exercising dogs

Recent studies suggest pH sampled by arterial chemoreceptors may not equal that sampled by external pH electrodes, because the uncatalyzed hydration of CO2 in plasma is a slow reaction (t 1/2 approximately 9 S). The importance of this reaction rate to ventilatory control (particularly during exercise) is not known. We studied the effect of catalyzing the CO2-pH reaction in three awake exercising dogs with chronic tracheostomies and carotid loops; the dogs were trained to run on a treadmill. Respiration frequency, tidal volume, total ventilation, and end-tidal partial pressure of CO2 (PCO2) were continuously monitored. Periodically, carotid artery blood was drawn and analyzed for partial pressure of O2 (PO2), PCO2, pH, and plasma carbonic anhydrase (CA) activity. Measurements were made during steady-state exercise (3 mph and 10% grade), during a control period, after injection of a 5 ml bolus of saline, and after injection of 5 mg/kg of bovine CA dissolved in 5 ml of saline. This dose of CA increased the reaction rate by more than 80-fold. Neither the control nor the CA injections significantly altered the ventilatory parameters. Saline and CA date differed by less than 5% in ventilation, 1 Torr in arterial PCO2, 0.01 in pH units, and 1.5 Torr in end-tidal PCO2. Thus the of CO2 hydration in plasma is not a significant factor in ventilatory control.     

Validation of a maskless CO2-response test for sleep and infant studies

The Hazinski method is an indirect, noninvasive, and maskless CO2-response test useful in infants or during sleep. It measures the classic CO2-response slope (i.e., delta VI/delta PCO2) divided by resting ventilation Sr = (VI'--VI')/(VI'.delta PCO2) between low (')- and high (')-inspired CO2 as the fractional increase of alveolar ventilation per Torr rise of PCO2. In steady states when CO2 excretion (VCO2') = VCO2', Hazinski CO2-response slope (Sr) may be computed from the alveolar exchange equation as Sr = (PACO2'--PICO2')/(PACO2'--PICO2') where PICO2 is inspired PCO2. To avoid use of a mask or mouthpiece, the subject breathes from a hood in which CO2 is mixed with inspired air and a transcutaneous CO2 electrode is used to estimate alveolar PCO2 (PACO2). To test the validity of this method, we compared the slopes measured simultaneously by the Hazinski and standard steady-state methods using a pneumotachograph, mask, and end-tidal, arterial, and four transcutaneous PCO2 samples in 15-min steady-state challenges at PICO2 23.5 +/- 4.5 and 37 +/- 4.1 Torr. Sr was computed using PACO2 and arterial PCO2 (PaCO2) as well as with the four skin PCO2 (PSCO2) values. After correction for apparatus dead space, the standard method was normalized to resting VI = 1, and its CO2 slope was designated directly measured normalized CO2 slope (Sx), permitting error to be calculated as Sr/Sx.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial-alveolar CO2 equilibration in exercising dogs during prolonged rebreathing

Arterial-alveolar equilibration of CO2 during exercise was studied by normoxic CO2 rebreathing in six dogs prepared with a chronic tracheostomy and exteriorized carotid loop and trained to run on a treadmill. In 153 simultaneous measurements of PCO2 in arterial blood (PaCO2) and end-tidal gas (PE'CO2) obtained in 46 rebreathing periods at three levels of mild-to-moderate steady-state exercise, the mean PCO2 difference (PaCO2-PE'CO2) was -1.0 +/- 1.0 (SD) Torr and was not related to O2 uptake or to the level of PaCO2 (30-68 Torr). The small negative PaCO2-PE'CO2 is attributed to the lung-to-carotid artery transit time delay which must be taken into account when both PaCO2 and PE'CO2 are continuously rising during rebreathing (average rate 0.22 Torr/s). Assuming that blood-gas equilibrium for CO2 was complete, a lung-to-carotid artery circulation time of 4.6 s accounts for the observed uncorrected PaCO2-PE'CO2 of -1.0 Torr. The results are interpreted to indicate that in rebreathing equilibrium PCO2 in arterial blood and alveolar gas are essentially identical. This conclusion is at variance with previous studies in exercising humans during rebreathing but is in full agreement with our recent findings in resting dogs.     

Awake baboon's ventilatory response to venous and inhaled CO2 loading.

Steady-state ventilatory responses to CO2 in trained awake baboons were studied to determine the response to a venous CO2 load. CO2 was loaded either directly into the venous blood through an arteriovenous shunt or by addition to the inhaled air. The two modes of loading were adjusted to produce the same increase in minute volume. Minute volume, tidal volume respiratory frequency, end-tidal PCO2, PaCO2, and pHa were measured. PaCO2 and PETCO2 increased the same amount during the two modes of CO2 loading; thus, the response to changes in arterial PCO2, deltaVE/deltaPaCO2, was the same. I conclude that the ventilatory response to venous CO2 loading occurs only through the change in mean arterial PCO2 and thus it is unlikely that there are any important venous CO2 receptors.     

Regulation of arterial PCO2 during intravenous CO2 loading.

Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by "conventional" airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite "sensitivity" when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2.     

Cardiopulmonary response to extracorporeal venous CO2 removal in awake spontaneously breathing dogs

The ventilatory response to a reduction in mixed venous PCO2 has been reported to be a decrease in breathing even to the point of apnea with no change in arterial CO2 partial pressure (PaCO2), whereas a recent report in exercising dogs found a small but significant drop in PaCO2 (F. M. Bennett et al. J. Appl. Physiol. 56: 1335-1337, 1984). The purpose of the present study was to attempt to reconcile this discrepancy by carefully investigating the cardiopulmonary response to venous CO2 removal over the entire range from eupnea to the apneic threshold in awake, spontaneously breathing normoxic dogs. Six dogs with chronic tracheostomies were prepared with bilateral femoral arteriovenous shunts under general anesthesia. Following recovery, an extracorporeal venovenous bypass circuit, consisting of a roller pump and a silicone-membrane gas exchanger, was attached to the femoral venous cannulas. Cardiopulmonary responses were measured during removal of CO2 from the venous blood and during inhalation of low levels of CO2. Arterial PO2 was kept constant by adjusting inspired O2. The response to venous CO2 unloading was a reduction in PaCO2 and minute ventilation (VE). The slope of the response, delta VE/delta PaCO2, was the same as that observed during CO2 inhalation. This response continued linearly to the point of apnea without significant changes in cardiovascular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Likeness between respiratory responses on CO2 in conditions of natural breathing and voluntary-controlled mechanical ventilation

We did Read CO2 rebreathing tests in 8 adult males. Both at natural breathing, and at self-controlled mechanical ventilation, volunteers increased ventilation proportionally to growth end-tidal PCO2. Inside individual distinctions of responses to CO2 during controlled mechanical ventilation are result of the voluntary motor control.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

CO2 and mechanical factors reduce blood flow in a collapsed lung lobe

Left lower lobe-to-total blood flow ratio (Ql/QT) was measured with electromagnetic flow probes in anesthetized open-chest dogs. There was a 66% reduction in Ql/QT during lobar collapse, a 53% reduction during lobar ventilation hypoxia with pulmonary venous PO2 and PCO2 equal to mixed venous tensions, and a 45% reduction during a similar degree of ventilation hypoxia but with normal end-tidal PCO2. We concluded that the reduction in blood flow during lobar collapse is due predominantly to hypoxic vasoconstriction, but that this mechanism is augmented by the raised PCO2 and mechanical factors present during collapse.     

Blood-gas equilibration of CO2 and O2 in lungs of awake dogs during prolonged rebreathing

To reinvestigate the blood-gas CO2 equilibrium in lungs, rebreathing experiments were performed in five unanesthetized dogs prepared with a chronic tracheostomy and an exteriorized carotid loop. The rebreathing bag was initially filled with a gas mixture containing 6-8% CO2, 12, 21, or 39% O2, and 1% He in N2. During 4-6 min of rebreathing PO2 in the bag was kept constant by a controlled supply of O2 while PCO2 rose steadily from approximately 40 to 75 Torr. Spot samples of arterial blood were taken from the carotid loop; their PCO2 and PO2 were measured by electrodes and compared with the simultaneous values of end-tidal gas read from a mass spectrometer record. The mean end-tidal-to-arterial PO2 differences averaging 16, 4, and 0 Torr with bag PO2 about 260, 130, and 75 Torr, respectively, were in accordance with a venous admixture of about 1%. No substantial PCO2 differences between arterial blood and end-tidal gas (PaCO2 - PE'CO2) were found. The mean PaCO2 - PE'CO2 of 266 measurements in 70 rebreathing periods was -0.4 +/- 1.4 (SD) Torr. There was no correlation between PaCO2 - PE'CO2 and the level of arterial PCO2 or PO2. The mean PaCO2 - PE'CO2 became +0.1 Torr when the blood transit time from lungs to carotid artery (estimated at 6 s) and the rate of rise of bag PCO2 (4.5 Torr/min) were taken into account. These experimental results do not confirm the presence of significant PCO2 differences between arterial blood and alveolar gas in rebreathing equilibrium.     

Almitrine bismesylate and the central and peripheral ventilatory response to CO2

Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem.     

Effect of airway impedance on CO2 retention and respiratory muscle activity during NREM sleep

We hypothesized that a sleep-induced increase in mechanical impedance contributes to CO2 retention and respiratory muscle recruitment during non-rapid-eye-movement (NREM) sleep. The effect NREM sleep on respiratory muscle activity and CO2 retention was measured in healthy subjects who increased maximum total pulmonary resistance (RLmax, 1-81 cmH2O.l-1.s) from awake to NREM sleep. We determined the effects of this sleep-induced increase in airway impedance by steady-state inhalation of a reduced-density gas mixture (79% He-21% O2, He-O2). Both arterialized blood PCO2 (PaCO2) and end-tidal PCO2 (PETCO2) were measured. Inspiratory (EMGinsp) and expiratory (EMGexp) respiratory muscle electromyogram activity was measured. NREM sleep caused 1) RLmax to increase (7 +/- 3 vs. 39 +/- 28 cmH2O.l-1.s), 2) PaCO2 and/or PETCO2 to increase in all subjects (40 +/- 2 vs. 44 +/- 3 Torr), and 3) EMGinsp to increase in 8 of 9 subjects and EMGexp to increase in 9 of 17 subjects. Compared with steady-state air breathing during NREM sleep, steady-state He-O2 breathing 1) reduced RLmax by 38%, 2) decreased PaCO2 and PETCO2 by 2 Torr, and 3) decreased both EMGinsp (-20%) and EMGexp (-54%). We concluded that the sleep-induced increase in upper airway resistance accompanied by the absence of immediate load compensation is an important determinant of CO2 retention, which, in turn, may cause augmentation of inspiratory and expiratory muscle activity above waking levels during NREM sleep.     

CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.     

Effect of withdrawal of respiratory CO2 oscillations on respiratory control at rest

We examined the effect of sudden withdrawal of respiratory oscillations of arterial PCO2 (CO2 oscillations) at resting metabolic rate on the control of respiration in 11 anesthetized paralyzed vagotomized dogs in normoxic normocapnia. A double-lumen endotracheal tube was inserted so that the left and right lungs were ventilated independently. By alternately ventilating each lung, we could completely abolish CO2 oscillations without affecting the mean blood gas levels (withdrawal of CO2 oscillations). The CO2 oscillation was calculated from arterial pH oscillation measured by a rapidly responding intra-arterial pH electrode. Respiratory center output was monitored by use of a moving time average of the phrenic neurogram. A 3-min period of withdrawal of CO2 oscillations was bracketed by two control periods (simultaneous ventilation of lungs for 3 min) to avoid the confounding effect of the baseline drift in the respiratory center output. The amplitude of the CO2 oscillations in the control was 2.33 +/- 0.89 (SD) Torr. When the difference in the mean level of arterial PCO2 between the control and withdrawal of CO2 oscillations was minimized (-0.09 +/- 0.54 Torr; P greater than 0.25), we found negligible change in the minute phrenic activity during withdrawal of CO2 oscillations (-0.02 +/- 6.11% of the control, P greater than 0.98, n = 49; 99% confidence interval -2.36 to 2.32%). Thus we conclude that the maintenance of normal respiration at rest is not critically dependent on a phasic afferent input to the respiratory center arising from respiratory CO2 oscillations.     

Respiratory control in humans after 8 h of lowered arterial PO2, hemodilution, or carboxyhemoglobinemia.

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial PO2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal PO2 was held at 55 Torr and end-tidal PCO2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH (P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial PO2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.     

Carotid body denervation in dogs: eupnea and the ventilatory response to hyperoxic hypercapnia.

We assessed the time course of changes in eupneic arterial PCO(2) (Pa(CO(2))) and the ventilatory response to hyperoxic rebreathing after removal of the carotid bodies (CBX) in awake female dogs. Elimination of the ventilatory response to bolus intravenous injections of NaCN was used to confirm CBX status on each day of data collection. Relative to eupneic control (Pa(CO(2)) = 40 +/- 3 Torr), all seven dogs hypoventilated after CBX, reaching a maximum Pa(CO(2)) of 53 +/- 6 Torr by day 3 post-CBX. There was no significant recovery of eupneic Pa(CO(2)) over the ensuing 18 days. Relative to control, the hyperoxic CO(2) ventilatory (change in inspired minute ventilation/change in end-tidal PCO(2)) and tidal volume (change in tidal volume/ change in end-tidal PCO(2)) response slopes were decreased 40 +/- 15 and 35 +/- 20% by day 2 post-CBX. There was no recovery in the ventilatory or tidal volume response slopes to hyperoxic hypercapnia over the ensuing 19 days. We conclude that 1) the carotid bodies contribute approximately 40% of the eupneic drive to breathe and the ventilatory response to hyperoxic hypercapnia and 2) there is no recovery in the eupneic drive to breathe or the ventilatory response to hyperoxic hypercapnia after removal of the carotid chemoreceptors, indicating a lack of central or aortic chemoreceptor plasticity in the adult dog after CBX.     

Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study.

The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Ventilatory responses to intravenous and airway CO2 administration in anesthetized dogs

The ventilatory responses to steady-state venous CO2 loading (iv CO2) and CO2 inhalation have been observed in chloralose-urethan-anesthetized dogs. Intravenous CO2 was administered by increasing the CO2 fraction of gas ventilating a membrane gas exchanger in an arteriovenous bypass; blood flow rate was fixed at 30 ml/min. During the study, we identified a time-dependent hyperventilation in all 14 experimentally treated dogs and in 4 additional sham-treated dogs. When we tested 8 of these animals with a protocol having small progressive increments in iv CO2 loading rate, we observed a response approaching isocapnia during iv CO2 and a large hypocapnia when we returned to control conditions. The use of a randomized protocol in 6 animals demonstrated the necessity of accounting for this systematic base-line shift, because before doing so the response depended more on the passage of time than on the nature of the CO2 load. After this analytical adjustment was made, there was no significant difference between the respiratory controller gains (delta nu E/delta Paco2) for inhaled and iv CO2.