Effects of altered CSF [H+] on ventilatory responses to exercise in the awake goat

We investigated the effects of selective large changes in the acid-base environment of medullary chemoreceptors on the control of exercise hyperpnea in unanesthetized goats. Four intact and two carotid body-denervated goats underwent cisternal perfusion with mock cerebrospinal fluid (CSF) of markedly varying [HCO-3] (CSF [H+] = 21-95 neq/l; pH 7.68-7.02) until a new steady state of alveolar hypo- or hyperventilation was reached [arterial PCO2 (PaCO2) = 31-54 Torr]. Perfusion continued as the goats completed two levels of steady-state treadmill walking [2 to 4-fold increase in CO2 production (VCO2)]. With normal acid-base status in CSF, goats usually hyperventilated slightly from rest through exercise (-3 Torr PaCO2, rest to VCO2 = 1.1 l/min). Changing CSF perfusate [H+] changed the level of resting PaCO2 (+6 and -4 Torr), but with few exceptions, the regulation of PaCO2 during exercise (delta PaCO2/delta VCO2) remained similar regardless of the new ventilatory steady state imposed by changing CSF [H+]. Thus the gain (slope) of the ventilatory response to exercise (ratio of change in alveolar ventilation to change in VCO2) must have increased approximately 15% with decreased resting PaCO2 (acidic CSF) and decreased approximately 9% with increased resting PaCO2 (alkaline CSF). A similar effect of CSF [H+] on resting PaCO2 and on delta PaCO2/VCO2 during exercise also occurred in two carotid body-denervated goats. Our results show that alteration of the gain of the ventilatory response to exercise occurs on acute alterations in resting PaCO2 set point (via changing CSF [H+]) and that the primary stimuli to exercise hyperpnea can operate independently of central or peripheral chemoreception.     

Ventilatory control during exercise with increased respiratory dead space in goats

Our objectives were to determine 1) the effects of increased respiratory dead space (VD) on the ventilatory response to exercise and 2) whether changes in the ventilatory response are due to changes in chemoreceptor feedback (rest to exercise) vs. changes in the feedforward exercise stimulus. Steady-state ventilation (VI) and arterial blood gas responses to mild or moderate hyperoxic exercise in goats were compared with and without increased VD. Responses were compared using a simple mathematical model with the following assumptions: 1) steady state, 2) linear CO2 chemoreceptor feedback, 3) linear feedforward exercise stimulus proportional to CO2 production (VCO2) and characterized by an exercise gain (Gex), and 4) additive exercise stimulus and CO2 feedback producing the system gain (Gsys = delta VI/delta VCO2). Model predictions at constant Gex [assuming VD-to-tidal volume (VT) ratio independent of VCO2] are that increased VD/VT will 1) increase arterial PCO2 (PaCO2) and VI at rest and 2) increase Gsys via changes in chemoreceptor feedback due to a small increase in the PaCO2 vs. VCO2 slope. Experimental results indicate that increased VD increased VD/VT, PaCO2, and VI at rest and increased Gsys during exercise. However, measurable changes in the PaCO2 vs. VCO2 slope occurred only at high VD/VT or running speeds. Gex was estimated at each VD for each goat by using the model in conjunction with experimental measurements. With 0.2 liter VD, Gex increased 40% (P less than 0.01); with 0.6 liter VD, Gex increased 110% between 0 and 2.4 km/h and 5% grade (P less than 0.01) but not between 2.4 and 4.8 km/h. Thus, Gex is increased by VD through a limited range. In goats, increases in Gsys with increased VD result from increases in both Gex and CO2 chemoreceptor feedback. These results are consistent with other experimental treatments that increase the exercise ventilatory response, maintaining constant relative PaCO2 regulation, and suggest that a common mechanism linked to resting ventilatory drive modulates Gex.     

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.     

Effect of inspiratory resistive loading on control of ventilation during progressive exercise

Eight healthy volunteers performed gradational tests to exhaustion on a mechanically braked cycle ergometer, with and without the addition of an inspiratory resistive load. Mean slopes for linear ventilatory responses during loaded and unloaded exercise [change in minute ventilation per change in CO2 output (delta VE/delta VCO2)] measured below the anaerobic threshold were 24.1 +/- 1.3 (SE) = l/l of CO2 and 26.2 +/- 1.0 l/l of CO2, respectively (P greater than 0.10). During loaded exercise, decrements in VE, tidal volume, respiratory frequency, arterial O2 saturation, and increases in end-tidal CO2 tension were observed only when work loads exceeded 65% of the unloaded maximum. There was a significant correlation between the resting ventilatory response to hypercapnia delta VE/delta PCO2 and the ventilatory response to VCO2 during exercise (delta VE/delta VCO2; r = 0.88; P less than 0.05). The maximal inspiratory pressure generated during loading correlated with CO2 sensitivity at rest (r = 0.91; P less than 0.05) and with exercise ventilation (delta VE/delta VCO2; r = 0.83; P less than 0.05). Although resistive loading did not alter O2 uptake (VO2) or heart rate (HR) as a function of work load, maximal VO2, HR, and exercise tolerance were decreased to 90% of control values. We conclude that a modest inspiratory resistive load reduces maximum exercise capacity and that CO2 responsiveness may play a role in the control of breathing during exercise when airway resistance is artificially increased.     

Exercise-induced hypercapnia in the horse

The effects of exercise intensity and duration on blood gases in thoroughbred horses were studied to characterize the apparent exercise-induced failure in pulmonary gas exchange that occurs in these animals. In response to 2 min of exercise, arterial CO2 tension (PaCO2) decreased in mild and moderate exercise, returned to normocapnic levels in moderate to heavy exercise, and rose 5-10 Torr above resting values during very heavy exercise when CO2 production (VCO2) exceeded 20 times the resting value, and mixed venous CO2 tension approximated 140 Torr. Exercise-induced hypoxemia occurred at the onset of heavy exercise and was associated with the absence of a hyperventilatory response and an alveolar-arterial PO2 difference that increased four to six times above rest with very heavy exercise. PaCO2 was related to VCO2 but not fb, as changes in breathing frequency (fb) of 8-20 breaths/min at comparable VCO2 did not affect PaCO2. Prolonging very heavy exercise from 2 to 4 min caused a severe metabolic acidosis (arterial pH less than 7.15) and hypoxemia was maintained; however, CO2 was no longer retained, as PaCO2 gradually fell to below resting levels, due to an increased tidal volume at constant fb. We conclude that a truly compensatory hyperventilation to very heavy exercise in the horse is not achieved because of the excessive volumes and flow rates required by their extraordinarily high VCO2 and VO2. On the other hand, the frank CO2 retention during short-term high-intensity exercise occurs even though the horse is not apparently mechanically obligated to tolerate it.     

Model implications of gas exchange dynamics on blood gases in incremental exercise

In humans, arterial PCO2 (PaCO2) has been demonstrated to be regulated at or near resting levels in the steady state of moderate exercise (i.e., for work rates not associated with a sustained lactic acidosis). To determine how PaCO2 might be expected to behave under the nonsteady-state conditions of incremental exercise testing, the influence of the dynamic characteristics of the primary variables that determine PaCO2 was explored by means of computer modeling. We constructed a dynamic model that utilized previously reported experimental estimates for the kinetic response parameters of ventilation (VE) and CO2 output (VCO2). In response to incremental work rate forcings, the model yielded an increase in PaCO2, which reflected the disparity between the VE and VCO2 time constants; this hypercapnic condition was maintained despite VE and VCO2 both increasing linearly with respect to the input work rate profile. The degree of hypercapnia increased with the rate of the incremental forcing, reaching 9 Torr for a 50-W/min forcing. In conclusion, therefore, sustained increases in PaCO2 during nonsteady-state incremental exercise should be interpreted with caution, because this is the predicted response even in subjects with normal ventilatory control and lung function.     

Control of exercise hyperpnea during hypercapnia in humans

Previous studies have yielded conflicting results on the ventilatory response to CO2 during muscular exercise. To obviate possible experimental errors contributing to such variability, we have examined the CO2-exercise interaction in terms of the ventilatory response to exercise under conditions of controlled hypercapnia. Eight healthy male volunteers underwent a sequence of 5-min incremental treadmill exercise runs from rest up to a maximum CO2 output (VCO2) of approximately 1.5 l . min-1 in four successive steps. The arterial PCO2 (PaCO2) at rest was stabilized at the control level or up to 14 Torr above control by adding 0-6% CO2 to the inspired air. Arterial isocapnia (SD = 1.2 Torr) throughout each exercise run was maintained by continual adjustment of the inspired PCO2. At all PaCO2 levels the response in total ventilation (VE) was linearly related to exercise VCO2. Hypercapnia resulted in corresponding increases in both the slope (S) and zero intercept (V0) of the VE-VCO2 curve; these being directly proportional to the rise in PaCO2 (means +/- SE: delta S/ delta PaCO2, 2.73 +/- 0.28 Torr-1; delta V0/ delta PaCO2, 1.67 +/- 0.18 l . min-1 . Torr-1). Thus the ventilatory response to concomitant hypercapnia and exercise was characterized by a synergistic (additive plus multiplicative) effect, suggesting a positive interaction between these stimuli. The increased exercise sensitivity in hypercapnia is qualitatively consistent with the hypothesis that VE is controlled to minimize the conflicting challenges due to chemical drive and the mechanical work of breathing (Poon, C. S. In: Modelling and Control of Breathing, New York: Elsevier, 1983, p. 189-196).     

Ventilatory and PaCO2 responses to voluntary and electrically induced leg exercise

We studied the role of central command mediation of exercise hyperpnea by comparing the ventilatory and arterial CO2 partial pressure (PaCO2) responses to voluntary (ExV) and electrically induced (ExE) muscle contractions in normal, awake human subjects. We hypothesized that if central command signals are critical to a normal ventilatory response, then ExE should cause a slower ventilatory response resulting in hypercapnia at the onset of exercise. ExE was induced through surface electrodes placed over the quadriceps and hamstring muscles. ExE and ExV produced leg extension (40/min) against a spring load that increased CO2 production (VCO2) 100-1,000 ml/min above resting level. PaCO2 and arterial pH during work transitions and in the steady state did not differ significantly from rest (P greater than 0.05) or between ExE and ExV. The temporal pattern of ventilation, tidal volume, breathing frequency, and inspired and expired times, and the ventilation-VCO2 relationship were similar between ExE and ExV. We conclude that since central command was reduced and/or eliminated by ExE, central command is not requisite for the precise matching of alveolar ventilation to increases in VCO2 during low-intensity muscle contractions.     

Background ventilatory stimulus as a determinant of load compensation

Compensation for inspiratory flow-resistive loading was compared during progressive hypercapnia and incremental exercise to determine the effect of changing the background ventilatory stimulus and to assess the influence of the interindividual variability of the unloaded CO2 response on evaluation of load compensation in normal subjects. During progressive hypercapnia, ventilatory response was incompletely defended with loading (mean unloaded delta VE/delta PCO2 = 3.02 +/- 2.29, loaded = 1.60 +/- 0.67 1.min-1.Torr-1 CO2, where VE is minute ventilation and PCO2 is CO2 partial pressure; P less than 0.01). Furthermore the degree of defense of ventilation with loading was inversely correlated with the magnitude of the unloaded CO2 response. During exercise, loading produced no depression in ventilatory response (mean delta VE/delta VCO2 unloaded = 20.5 +/- 1.9, loaded = 19.2 +/- 2.5 l.min-1.l-1.min-1 CO2 where VCO is CO2 production; P = NS), and no relationship was demonstrated between degree of defense of the exercise ventilatory response and the unloaded CO2 response. Differences in load compensation during CO2 rebreathing and exercise suggest the presence of independent ventilatory control mechanisms in these states. The type of background ventilatory stimulus should therefore be considered in load compensation assessment.     

Effect of high-intensity exercise on the VE-VCO2 relationship

The intrinsic relationship between ventilation (VE) and carbon dioxide output (VCO2) is described by the modified alveolar ventilation equation VE = VCO2 k/PaCO2(1-VD/VT) where PaCO2 is the partial pressure of CO2 in the arterial blood and VD/VT is the dead space fraction of the tidal volume. Previous investigators have reported that high-intensity exercise uncouples VE from VCO2; however, they did not measure the PaCO2 and VD/VT components of the overall relationship. In an attempt to provide a more complete analysis of the effects of high-intensity exercise on the VE-VCO2 relationship, we undertook an investigation where five subjects volunteered to perform three steady-state tests (SS1, SS2, SS3) at 60 W. One week after SS1 each subject was required to perform repeated 1-min bouts of exercise corresponding to a work rate of approximately 140% of maximal oxygen uptake (VO2max). Two and 24 h later the subjects performed SS2 and SS3, respectively. This exercise intervention caused PaCO2 during SS2 and SS3 to be regulated (P less than 0.01) approximately 4 Torr below the control (SS1) value of 38.8 Torr. Additionally, significant alterations were noted for VCO2 with corresponding values of 1.15 (SS1), 1.10 (SS2), and 1.04 (SS3) l/min. No changes were noted in either VD/VT or VE. In summary, it seems reasonable to suggest that the disproportionate increase in VE with respect to VCO2 noted in earlier work does not reflect an uncoupling. Rather the slope of the VE-VCO2 relationship is increased in a predictable manner as described by the modified alveolar ventilation equation.     

Temporal pattern of arterial CO2 partial pressure during exercise in humans

The major objective of this study was to test the hypothesis that arterial CO2 partial pressure (PaCO2) does not change in transitions from rest to steady-state exercise and between two levels of exercise. Nine young adults exercised on a treadmill or a bicycle (sit or supine) for 5 min at a mild work load (heart rate = 90 beats X min-1) and then 3 min at a moderate work load (heart rate = 150 beats X min-1). In some studies the moderate work load preceded the mild work load. Arterial blood was sampled from a catheterized artery. During all exercise tasks isocapnia was not strictly maintained (F greater than 4.0, P less than 0.001). For example, a 1-to 2-Torr hypocapnia was the dominant trend during the first 15-45 s after increasing treadmill speed, and a transient hypercapnia was most prevalent when treadmill speed was decreased. During steady-state exercise PaCO2 did not deviate by more than 1-3 Torr from PaCO2 during any resting posture, and PaCO2 differences between exercise intensities and conditions did not exceed 1-2 Torr. A mouthpiece-breathing valve system was not used in most studies, but when this system was used, it did not consistently affect exercise PaCO2. Increasing inspired O2 to 40% likewise did not consistently alter exercise PaCO2. Failure to maintain isocapnia throughout exercise indicates that the matching of alveolar ventilation (VA) to lung CO2 delivery is not exquisitely precise. Accordingly it is inappropriate to base theories of the exercise hyperpnea on the heretofore contention of precise matching.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of neural afferents from working limbs in exercise hyperpnea

To determine the role of reflex discharge of afferent nerves from the working limbs in the exercise hyperpnea, 1.5- to 2.5-min periods of phasic hindlimb muscle contraction were induced in anesthetized cats by bilateral electrical stimulation of ventral roots L7, S1, and S2. Expired minute ventilation (VE) and end-tidal PCO2 (PETCO2) were computed breath by breath, and mean arterial PCO2 (PaCO2) was determined from discrete blood samples and, also in most animals, by continuous measurement with an indwelling PCO2 electrode. During exercise VE rose progressively with a half time averaging approximately 30 s, but a large abrupt increase in breathing at exercise onset typically did not occur. Mean PaCO2 and PETCO2 remained within approximately 1 Torr of control levels across the work-exercise transition, and PaCO2 was regulated at an isocapnic level after VE had achieved its peak value. Sectioning the spinal cord at L1-L2 did not alter these response characteristics. Thus, reflex discharge of afferent nerves from the exercising limbs was not requisite for the matching of ventilation to metabolic demand during exercise.     

Ventilatory changes during exercise and arterial PCO2 oscillations in chronic airway obstruction patients

Ventilatory kinetics during exercise (30 W for 6 min) were studied in 3 asthmatics, 14 patients with chronic airway obstruction (11 with bronchial or type B disease, 3 with emphysematous or type A disease), and in 5 normal age-matched controls. The measure of ventilatory increase during early exercise, alpha 1-3%, was calculated as (avg minute ventilation over 1st-3rd min of exercise--resting minute ventilation)/(avg minute ventilation over 4th-6th min of exercise--resting minute ventilation) X 100. Arterial pH, PO2, and PCO2 (PaCO2) were measured in vitro at rest and within 20 s of termination of exercise. Respiratory PaCO2 oscillations had previously been monitored at rest in the patients (indirectly as in vivo arterial pH, using a fast-response pH electrode) and quantified by upslope (delta PaCO2/delta t). alpha 1-3% was normal in asthmatics (whose respiratory oscillations as a group showed least attenuation) and in type A patients (whose respiratory oscillations as a group were most attenuated). In type B patients reduction in alpha 1-3% correlated with attenuation of delta PaCO2/delta t (r = 0.75; P less than 0.01). There was no significant correlation between delta PaCO2/delta t and change of in vitro PaCO2 from rest to the immediate postexercise period. These findings are consistent with the hypothesis that attenuation of delta PaCO2/delta t slows ventilatory kinetics during exercise in type B but not type A patients. Intact respiratory oscillations are not necessary for CO2 homeostasis after the first few minutes of exercise.     

Depression of ventilation hypoxia in man.

In five normal male subjects, ventilation, PaO2, and PaCO2 were measured during the rapid progressive isocapnic production of hypoxia (5 min) and during the equally rapid isocapnic reversal of hypoxia. At similar PaO2, PaCO2, and pH, ventilation was less at a time when alveolar PO2 was increasing than when alveolar PO2 was decreasing. We interpret these results as showing that human ventilation is depressed by mild-to-moderate hypoxia (40-60 Torr), that such depression is probably central, and that it is ordinarily masked by peripheral chemoreceptor stimulation. We are not able to distinguish whether the ventilatory depression is caused by decreased central chemoreceptor PCO2 due to an increase in cerebral flow, direct hypoxic depressing of the central respiratory mechanism, or both.     

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 blood gases and acid-base status of dogs during graded dynamic exercise

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carotid body excision significantly changes ventilatory control in awake rats

We determined the effects of carotid body excision (CBX) on eupneic ventilation and the ventilatory responses to acute hypoxia, hyperoxia, and chronic hypoxia in unanesthetized rats. Arterial PCO2 (PaCO2) and calculated minute alveolar ventilation to minute metabolic CO2 production (VA/VCO2) ratio were used to determine the ventilatory responses. The effects of CBX and sham operation were compared with intact controls (PaCO2 = 40.0 +/- 0.1 Torr, mean +/- 95% confidence limits, and VA/VCO2 = 21.6 +/- 0.1). CBX rats showed 1) chronic hypoventilation with respiratory acidosis, which was maintained for at least 75 days after surgery (PaCO2 = 48.4 +/- 1.1 Torr and VA/VCO2 = 17.9 +/- 0.4), 2) hyperventilation in response to acute hyperoxia vs. hypoventilation in intact rats, 3) an attenuated increase in VA/VCO2 in acute hypoxemia (arterial PO2 approximately equal to 49 Torr), which was 31% of the 8.7 +/- 0.3 increase in VA/VCO2 observed in control rats, 4) no ventilatory acclimatization between 1 and 24 h hypoxia, whereas intact rats had a further 7.5 +/- 1.5 increase in VA/VCO2, 5) a decreased PaCO2 upon acute restoration of normoxia after 24 h hypoxia in contrast to an increased PaCO2 in controls. We conclude that in rats carotid body chemoreceptors are essential to maintain normal eupneic ventilation and to the process of ventilatory acclimatization to chronic hypoxia.     

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.     

Is the hyperpnea of muscular contractions critically dependent on spinal afferents?

We studied the role of spinal afferent pathways in the hyperpnea of electrically induced muscle contractions (ExE). The ventilatory (VE) and arterial CO2 partial pressure (PaCO2) responses were measured at rest and during two levels of ExE in awake human paraplegic subjects with clinically complete lesions of the spinal cord (range T4-T11). We hypothesized that if peripheral neural drive is critical to a normal ventilatory response, then ExE in the absence of intact pathways should cause a lower ventilatory response resulting in hypercapnia at the onset of ExE. ExE was induced by stimulation of the quadriceps and hamstring muscles that approximately doubled the resting level of CO2 production (VCO2). PaCO2 during work transitions and in the latter stages of ExE did not differ significantly from that at rest. Arterial pH progressively declined over time during ExE (P less than 0.01) as a result of increased lactate concentration (P less than 0.01). The linear relationship between VE and VCO2 was similar to that found for normal human subjects during ExE (P = 0.73). These data suggest that VE and presumably alveolar ventilation (VA) can be appropriately matched to VCO2 during low-intensity muscle contractions of the lower extremities in the absence of intact spinal afferent pathways. Moreover, since it is unlikely that postulated "central command" mechanisms were initiated during ExE in these paraplegic subjects, the data provide support for our previous conclusion that central command is not obligatory for matching VA to VCO2 (J. Appl. Physiol. 64: 218-225, 1988).     

Role of carotid chemoreceptors and pulmonary vagal afferents during helium-oxygen breathing in ponies

Our purpose was to assess compensatory breathing responses to airway resistance unloading in ponies. We hypothesized that the carotid bodies and hilar nerve afferents, respectively, sense chemical and mechanical changes caused by unloading, hence carotid body-denervated (CBD) and hilar nerve-denervated ponies (HND) might demonstrate greater ventilatory responses when decreasing resistance. At rest and during treadmill exercise, resistance was transiently reduced approximately 40% in five normal, seven CBD, and five HND ponies by breathing gas of 79% He-21% O2 (He-O2). In all groups at rest, He-O2 breathing did not consistently change ventilation (VE), breathing frequency (f), tidal volume (VT), or arterial PCO2 (PaCO2) from room air-breathing levels. During treadmill exercise at 1.8 mph-5% grade in normal and HND ponies, He-O2 breathing did not change PaCO2 but at moderate (6 mph-5% grade), and heavy (8 mph-8% grade) work loads, absolute PaCO2 tended to decrease by 1 min of resistance unloading. delta PaCO2 calculated as room air minus He-O2 breathing levels at 1 min demonstrated significant changes in PaCO2 during exercise resistance unloading (P less than 0.05). No difference between normal and HND ponies was found in exercise delta PaCO2 responses (P greater than 0.10); however, in CBD ponies, the delta PaCO2 during unloading was greater at any given work load (P less than 0.05), suggesting finer regulation of PaCO2 in ponies with intact carotid bodies. During heavy exercise VE and f increased during He-O2 breathing in all three groups of ponies (P less than 0.05), although there were no significant differences between groups (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)