Focal acidosis in the pre-Botzinger complex area of awake goats induces a mild tachypnea.

There are widespread chemosensitive areas in the brain with varying effects on breathing. In the awake goat, microdialyzing (MD) 50% CO(2) at multiple sites within the medullary raphe increases pulmonary ventilation (Vi), blood pressure, heart rate, and metabolic rate (Vo(2)) (11), while MD in the rostral and caudal cerebellar fastigial nucleus has a stimulating and depressant effect, respectively, on these variables (17). In the anesthetized cat, the pre-Bötzinger complex (preBötzC), a hypothesized respiratory rhythm generator, increases phrenic nerve activity after an acetazolamide-induced acidosis (31, 32). To gain insight into the effects of focal acidosis (FA) within the preBötzC during physiological conditions, we tested the hypothesis that FA in the preBötzC during wakefulness would stimulate breathing, by increasing respiratory frequency (f). Microtubules were bilaterally implanted into the preBötzC of 10 goats. Unilateral MD of mock cerebral spinal fluid equilibrated with 6.4% CO(2) did not affect Vi, tidal volume (Vt), or f. Unilateral MD of 25 and 50% CO(2) significantly increased Vi and f by 10% (P < 0.05, n = 10, 17 trials), but Vt was unaffected. Bilateral MD of 6.4, 25, or 50% CO(2) did not significantly affect Vi, Vt, or f (P > 0.05, n = 6, 6 trials). MD of 80% CO(2) caused a 180% increase in f and severe disruptions in airflow (n = 2). MD of any level of CO(2) did not result in any significant changes in mean arterial blood pressure, heart rate, or Vo(2). Thus the data suggest that the preBötzC area is chemosensitive, but the responses to FA at this site are unique compared with other chemosensitive sites.

Normal breathing pattern and arterial blood gases in awake and sleeping goats after near total destruction of the presumed pre-Botzinger complex and the surrounding region.

Abrupt neurotoxic destruction of >70% of the pre-Bötzinger complex (preBötzC) in awake goats results in respiratory and cardiac failure (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV. J Appl Physiol 97: 1629-1636, 2004). However, in reduced preparations, rhythmic respiratory activity has been found in other areas of the brain stem (Huang Q, St. John WM. J Appl Physiol 64: 1405-1411, 1988; Janczewski WA, Feldman JL. J Physiol 570: 407-420, 2006; Lieske SP, Thoby-Brisson M, Telgkamo P, Ramierz JM. Nature Neurosci 3: 600-607, 2000; St. John WM, Bledsoe TA. J Appl Physiol 59: 684-690, 1985); thus we hypothesized that, when the preBötzC is destroyed incrementally over weeks, time-dependent plasticity within the respiratory network will result in a respiratory rhythm capable of maintaining normal blood gases. Microtubules were bilaterally implanted into the presumed preBötzC of seven goats. After recovery from surgery, studies were completed to establish baseline values for respiratory parameters. At weekly intervals, increasing volumes (in order 0.5, 1, 5, and 10 microl) of ibotenic acid (IA; 50 mM) were then injected into the preBötzC. All IA injections resulted in an acute tachypnea and dysrhythmia featuring augmented breaths, apneas, and increased breath-to-breath variation in breathing. In studies at night, apneas were nearly all central and occurred in the awake state. Breath-to-breath variation in breathing was greater (P < 0.05) during wakefulness than during non-rapid eye movement sleep. However, one week after the final IA injection, the breathing pattern, breath-to-breath variation, and arterial blood gases and pH were unchanged from baseline, but there was a 20% decrease in respiratory frequency (f) and CO(2) sensitivity (P < 0.05), as well as a 40% decrease in the ventilatory response to hypoxia (P < 0.001). In subsequent histological analysis of the presumed preBötzC region of lesioned goats, it was determined that there was a 90 and 92% reduction from control goats in total and neurokinin-1 receptor neurons, respectively. Therefore, it was concluded that 1) the dysrhythmic effects on breathing are state dependent; and 2) after incremental, near total destruction of the presumed preBötzC region, time-dependent plasticity within the respiratory network provides a rhythm capable of sustaining normal arterial blood gases.

The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats.

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO(2)-H(+) sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N=9) for injection (0.5-10 microl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO(2)-H(+) sensitivity did not differ significantly (P>0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic Pa(CO2) (P>0.10). The coefficient of variation of eupneic Pa(CO2) was 4.0+/-0.6 and 3.7+/-0.4% over the 2 weeks before and after the lesion, respectively. CO(2)-H(+) sensitivity expressed as inspired ventilation/Pa(CO2) decreased from 2.15+/-0.17 pre-lesion to 1.58+/-0.26 l/(min mmHg) 3-6 days post-lesion (P<0.02, -27%). There was no significant (P>0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P<0.05) the day-to-day variability of this index by nearly 100%. When CO(2) sensitivity was expressed as elevated inspired CO(2)/room air V (I), values at 7%, but not 3 and 5% inspired CO(2), were reduced and more variable (P<0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia.

CO2/H+ chemoreceptors in the cerebellar fastigial nucleus do not uniformly affect breathing of awake goats.

Our objective in this study was to test the hypothesis that focal acidosis (FA) in the cerebellar fastigial nucleus (CFN) of awake goats arising from global brain acidosis induced by increasing inspired CO2 will increase breathing. FA was created by reverse microdialysis of mock cerebral spinal fluid, equilibrated with 6.4, 25, 50, or 80% CO2 through chronically implanted microtubules (cannula). Dialysis with 6.4% CO2 had no significant effects on any physiological parameters. However, microdialysis at higher levels of CO2 increased pulmonary ventilation (V(I)) in one group of studies and decreased V(I) in a second group and the difference between the groups was significant (t = 9.16, P < 0.001). In one group of studies (n = 8), FA with 50 and 80% CO2 significantly increased (P < 0.05) Vi by 16 and 12%, respectively, and significantly increased (P < 0.05) heart rate by 13 and 9%, respectively. In contrast, in another group of studies (n = 6), FA with 25 and 50% CO2 significantly decreased (P < 0.05) Vi by 7 and 10%, respectively. In this group oxygen consumption was decreased during dialysis with 80% CO2. On the basis of histology, we estimate that the increased and decreased responses were associated with FA primarily in the rCFN and cCFN, respectively. We conclude that there are CO2/H+-sensitive neurons in the CFN that do not uniformly affect breathing. In addition, the significant changes in heart rate and oxygen consumption during FA indicate that the CFN can also influence non-respiratory-related control systems.

Lesions in the cerebellar fastigial nucleus have a small effect on the hyperpnea needed to meet the gas exchange requirements of submaximal exercise.

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is necessary for the hyperpnea to meet the gas exchange needs of submaximal exercise. Bilateral stainless steel microtubules were implanted in the cerebellum inside (n = 12) or outside (n = 2) the CFN for injection (0.5 to 10 microl) of the neurotoxin ibotenic acid. All goats had difficulty maintaining normal posture and walking for up to 1 mo after the implantation of the microtubules and again for hours or days after the neurotoxin was injected. Postmortem histology indicated there were 55% fewer living neurons (P < 0.001, n = 9, 3,720 +/- 553 vs. 1,670 +/- 192) in the CFN of the experimental goats compared with a control group of goats. As is typical for goats before implantation of the microtubules, the decrease in arterial Pco(2) from rest during mild and moderate treadmill exercise was 2.0 +/- 0.39 and 3.5 +/- 0.45 Torr, respectively. Implantation of the microtubules did not significantly change this exercise hyperventilation. However, neurotoxic lesioning with 10 mul ibotenic acid significantly (P < 0.05) attenuated the decrease in arterial Pco(2) by 1.3 and 2.8 Torr at the first and second workload, respectively. The modest attenuation of the exercise hypocapnia at both workloads in CFN-lesioned goats suggests that the CFN is part of the control system that enables the ventilatory response to meet the gas exchange requirements of submaximal exercise.

Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe.

Our aim was to determine the effects of carotid body denervation (CBD) on the ventilatory responses to focal acidosis and ibotenic acid (IA) injections into the medullary raphe area of awake, adult goats. Multiple microtubules were chronically implanted into the midline raphe area nuclei either before or after CBD. For up to 15 days after bilateral CBD, arterial PCO2 (PaCO2) (13.3 +/- 1.9 Torr) was increased (P < 0.001), and CO2 sensitivity (-53.0 +/- 6.4%) was decreased (P <0.001). Thereafter, resting PaCO2 and CO2 sensitivity returned (P <0.01) toward control, but PaCO2 remained elevated (4.8 +/- 1.9 Torr) and CO2 sensitivity reduced (-24.7 +/- 6.0%) > or =40 days after CBD. Focal acidosis (FA) at multiple medullary raphe area sites 23-44 days post-CBD with 50 or 80% CO(2) increased inspiratory flow (Vi), tidal volume (Vt), metabolic rate (VO2), and heart rate (HR) (P <0.05). The effects of FA with 50% CO2 after CBD did not differ from intact goats. However, CBD attenuated (P <0.05) the increase in Vi, Vt, and HR with 80% CO2, but it had no effect on the increase in VO2. Rostral but not caudal raphe area IA injections increased Vi, BP, and HR (P < 0.05), and these responses were accentuated (P <0.001) after CBD. CO2 sensitivity was attenuated (-20%; P <0.05) <7 days after IA injection, but thereafter it returned to prelesion values in CBD goats. We conclude the following: 1) the attenuated response to FA after CBD provides further evidence that the carotid bodies provide a tonic facilitory input into respiratory control centers, 2) the plasticity after CBD is not due to increased raphe chemoreceptor sensitivity, and 3) the "error-sensing" function of the carotid body blunts the effect of strong stimulation of the raphe.

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)

Arterial vs. rectal temperature in ponies: rest, exercise, CO2 inhalation, and thermal stresses.

We assessed in ponies the adequacy of using rectal (Tre) rather than arterial temperature (Tar) under conditions common to ventilatory control experiments, i.e., CO2 breathing, thermal stress, and particularly exercise. We were interested in whether, and to what extent, Tar-Tre differences could lead to errors in arterial blood gas corrections. At control environmental temperatures (Ta) of 5 degrees C in the winter and 21 degrees C in the summer, Tar and Tre (37.1 degrees C) did not differ (P greater than 0.05). Elevating winter or summer Ta by 10-18 degrees C for 2-days or lowering summer Ta by 9 degrees C (2-days) did not change Tar or Tre (P greater than 0.05). Furthermore, elevating inspired PCO2 to 42 Torr for 15 min did not alter Tar or Tre from control (P greater than 0.05). During treadmill exercise, at 1.8 mph 5% grade, Tar and Tre did not change significantly (P greater than 0.05) from rest by 11 min of work. At 3 mph 5% grade, Tar increased progressively by 0.3 degrees C (P less than 0.05) while Tre tended to increase 0.1 degree C by 11 min. During moderate exercise at 6 mph 5% grade, Tar increased 0.9 degree C (P less than 0.05) while Tre increased 0.25 degree C (P less than 0.05). Finally, by 6 min of heavy exercise at 8 mph 20% grade, Tar increased 2 degrees C (P less than 0.05) while Tre increased 0.5 degree C (P less than 0.05). The Tar-Tre differences during the latter three work loads were statistically significant (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Reciprocal activation of hypopharyngeal muscles and their effect on upper airway area.

We examined in awake goats, 1) with intact upper airways (UAW), the effect of altering chemical drive on pharyngeal constrictors [thyropharyngeus (TP) and hypopharyngeus (HP)] and a dilator [stylopharyngeus (SP)], and 2) with an isolated UAW, the effect of activation of these muscles on supraglottic UAW (UAW(SG)) area. During eupnea in nine goats with intact UAW, the TP and HP were active during expiration, whereas the SP exhibited tonic expiratory and phasic inspiratory activity. After mechanically induced apneas (MIA), TP activity increased (263%, P < 0.02), HP activity exhibited a small, varied response, and SP activity greatly decreased (10%, P < 0.02). During resumption of respiratory effort, all goats exhibited absent/reduced airflow, and when diaphragm activity was 95% of control, TP activity remained elevated (135%) and SP activity was reduced (56%, P < 0.02). During hypercapnia, 1) TP activity decreased (P < 0.02), 2) HP response varied, and 3) SP activity increased (P < 0.02). After MIA in six goats with isolated UAW, TP activity increased 198% (P < 0.02) and UAW(SG) area (endoscopically determined) decreased (to 15% of control, P < 0.02). During recovery from MIA, a correlation was found between UAW(SG) area and the ratio of SP to TP activity. We conclude that the reciprocal activation of mechanically opposing dilator and constrictor muscles in the hypopharynx is correlated to changes in the UAW(SG) area, and an imbalance in activity of these opposing muscles can lead to UAW(SG) narrowing.

Attenuated Hering-Breuer inflation reflex 4 years after pulmonary vagal denervation in ponies.

The purpose of this study was to determine whether there was any recovery of the Hering-Breuer inflation reflex in ponies between 2-4 wk and 3-4 yr after hilar nerve denervation (HND). Under anesthesia and before HND, airway occlusion after a 3-liter lung inflation lengthened the subsequent occluded breath by nearly 10 times the control breath duration. Between 2 wk and 3-4 yr after HND, this maneuver increased the duration of the occluded breath by only 2.5 times the control breath duration. Also under anesthesia, the airway was occluded at end expiration. This maneuver increased the duration of the subsequent inspiratory effort by 71% in hilar nerve intact ponies but by only 20-25% 2-4 wk and 3-4 yr after HND. For both tests, the pre- and post-HND differences were statistically significant (P less than 0.05), but there were no significant differences (P greater than 0.10) between 2-4 wk and 3-4 yr post-HND. In awake ponies, at rest and during mild and moderate treadmill exercise, breathing frequency was generally lower and inspiratory time was greater after relative to before HND. The inspiratory time-to-total cycle duration ratio was consistently increased by 0.10-0.15 after HND (P less than 0.05). There was no significant change in this ratio between 2-4 wk and 3-4 yr post-HND (P greater than 0.10). We conclude that the surgical procedure for HND used in this study does not permit any significant reinnervation, and there are no significant changes within the ventilatory control system to compensate for loss of hilar nerve afferents.

Effect of hilar nerve denervation on breathing and arterial PCO2 during CO2 inhalation.

We determined the effects of denervating the hilar branches (HND) of the vagus nerves on breathing and arterial PCO2 (PaCO2) in awake ponies during eupnea and when inspired PCO2 (PICO2) was increased to 14, 28, and 42 Torr. In five carotid chemoreceptor-intact ponies, breathing frequency (f) was less, whereas tidal volume (VT), inspiratory time (TI), and ratio of TI to total cycle time (TT) were greater 2-4 wk after HND than before HND. HND per se did not significantly affect PaCO2 at any level of PICO2, and the minute ventilation (VE)-PaCO2 response curve was not significantly altered by HND. Finally, the attenuation of a thermal tachypnea by elevated PICO2 was not altered by HND. Accordingly, in carotid chemoreceptor-intact ponies, the only HND effect on breathing was the change in pattern classically observed with attenuated lung volume feedback. There was no evidence suggestive of a PCO2-H+ sensory mechanism influencing VE, f, VT, or PaCO2. In ponies that had the carotid chemoreceptors denervated (CBD) 3 yr earlier, HND also decreased f, increased VT, TI, and TT, but did not alter the slope of the VE-PaCO2 response curve. However, at all levels of elevated PICO2, the arterial hypercapnia that had persistently been attenuated, since CBD was restored to normal by HND. The data suggest that during CO2 inhalation in CBD ponies a hilar-innervated mechanism influences PaCO2 by reducing physiological dead space to increase alveolar ventilation.

Role of hilar nerve afferents in hyperpnea of exercise.

The objective of this study was to determine the role of hilar nerve (lung vagal) afferents in the hyperpnea of exercise. Ten ponies were studied before and 2-4 wk and 3-12 mo after sectioning only the hilar branches of the vagus nerves (HND). After HND, lung volume feedback to the medullary centers was attenuated as indicated in the anesthetized state by 1) attenuation or absence of the Hering-Breuer inflation reflex (P less than 0.01) and 2) attenuation of the lengthened inspiratory time (TI) when the airway was occluded at end expiration (P less than 0.01). Moreover, after HND in the awake state, there was an increase in the ratio of TI to total cycle time (P less than 0.01). These changes verify a compromise in lung innervation comparable to cervical vagotomy. Resting arterial PCO2, PO2, and pH were not altered following HND (P greater than 0.10). Moreover, at three levels of mild and moderate treadmill exercise, no difference in either the temporal pattern or the absolute levels of arterial blood gases and arterial pH was found between pre- and post-HND studies (P greater than 0.10). In addition, minute ventilation (VE) at rest and during exercise was not altered by HND (P greater than 0.10). However, 2-4 wk after HND the increase in breathing frequency (f) during exercise was less, whereas the increase in tidal volume during exercise was greater than pre-HND (P less than 0.05). The reduced f was due to an increase in TI with no change in expiratory time. We conclude that lung afferents via the hilar nerves influence the pattern of breathing at rest and during exercise in ponies.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of reducing anatomic dead space on arterial PCO2 during CO2 inhalation.

Carotid body-denervated (CBD) ponies have a less than normal increase in arterial PCO2 (PaCO2) when inspired CO2 (PICO2) is increased, even when pulmonary ventilation (VE) and breathing frequency (f) are normal. We studied six tracheostomized ponies to determine whether this change 1) might be due to increased alveolar ventilation (VA) secondary to a reduction in upper airway dead space (VD) or 2) is dependent on an upper airway sensory mechanism. Three normal and three chronic CBD ponies were studied while they were breathing room air and at 14, 28, and 42 Torr PICO2. While the ponies were breathing room air, physiological VD was 483 and 255 ml during nares breathing (NBr) and tracheostomy breathing (TBr), respectively. However, at elevated PICO2, mixed expired PCO2 often exceeded PaCO2; thus we were unable to calculate physiological VD using the Bohr equation. At all PICO2 in normal ponies, PaCO2 was approximately 0.3 Torr greater during NBr than during TBr (P less than 0.05). In CBD ponies this NBr-TBr difference was only evident while breathing room air and at 28 Torr PICO2. At each elevated PICO2 during both NBr and TBr, the increase in PaCO2 above control was always less in CBD ponies than in normal ponies (P less than 0.01). The VE-PaCO2, f-PaCO2, and tidal volume-PaCO2 relationships did not differ between NBr and TBr (P greater than 0.10) nor did they differ between normal and CBD ponies (P greater than 0.10). We conclude that the attenuated increase in PaCO2 during CO2 inhalation after CBD is not due to a relative increase in VA secondary to reducing upper airway VD.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats.

To gain insight into why there are chemoreceptors at widespread sites in the brain, mircrotubules were chronically implanted at two or three sites in the medullary raphe nuclei of adult goats (n = 7). After >2 wk, microdialysis (MD) probes were inserted into the microtubules to create focal acidosis (FA) in the awake state using mock cerebral spinal fluid (mCSF) equilibrated with 6.4% (pH = 7.3), 50% (pH = 6.5), or 80% CO(2) (pH = 6.3), where MD with 50 and 80% CO(2) reduces tissue pH by 0.1 and 0.18 pH unit, respectively. There were no changes in all measured variables with MD with 6.4% at single or multiple raphe sites (P > 0.05). During FA at single raphe sites, only 80% CO(2) elicited physiological changes as inspiratory flow was 16.9% above (P < 0.05) control. However, FA with 50 and 80% CO(2) at multiple sites increased (P < 0.05) inspiratory flow by 18.4 and 30.1%, respectively, where 80% CO(2) also increased (P < 0.05) tidal volume, heart rate, CO(2) production, and O(2) consumption. FA with 80% CO(2) at multiple raphe sites also led to hyperventilation (-2 mmHg), indicating that FA had effects on breathing independent of an increased metabolic rate. We believe these findings suggest that the large ventilatory response to a global respiratory brain acidosis reflects the cumulative effect of stimulation at widespread chemoreceptor sites rather than a large stimulation at a single site. Additionally, focal acidification of raphe chemoreceptors appears to activate an established thermogenic response needed to offset the increased heat loss associated with the CO(2) hyperpnea.

Effect of multiple denervations on the exercise hyperpnea in awake ponies.

In three previously reported studies, we had documented that the normal exercise hyperventilation in ponies is accentuated by carotid body denervation (CBD), not affected by hilar nerve pulmonary vagal denervation (HND), and mildly attenuated by spinal cord ablation of the dorsal lateral columns at L2 (SA). In the present study, we hypothesized that if redundancy of control existed in exercising ponies, then multiple denervations of theoretically important pathways in the same animal might attenuate the ventilatory response to exercise in a way not predictable by the individual lesion experiments alone. There were three major findings in the various combinations of CBD, HND, and SA in ponies during treadmill exercise. First, the combination of CBD with HND or SA resulted generally in an accentuation of the hypocapnia during exercise that was predictable on the basis of CBD alone. However, in one pony that showed a hypercapnic exercise response after SA alone, CBD subsequently caused a greater exercise hypercapnia. Second, HND in a CBD or SA pony did not affect the exercise arterial PCO2 response, which is consistent with previous data showing the lack of an HND effect in otherwise intact ponies. Third, in ponies with all three denervations together, the predominant response was an increase, not a decrease, in the exercise hyperventilation; this increase was greater than that predicted from the individual lesions. We conclude that these data do not provide evidence of redundancy in mechanism for the exercise hyperpnea other than instances of carotid chemoreceptor error sensing when hypercapnia occurs during exercise.

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)

Respiratory muscle electromyogram responses to acute hypoxia in awake ponies.

We determined the effect of acute hypoxia on the ventilatory (VE) and electromyogram (EMG) responses of inspiratory (diaphragm) and expiratory (transversus abdominis) muscles in awake spontaneously breathing ponies. Eleven carotid body-intact (CBI) and six chronic carotid body-denervated (CBD) ponies were studied during normoxia (fractional inspired O2 concn [FIO2] = 0.21) and two levels of hypoxia (FIO2 approximately 0.15 and 0.12; 6-10 min/period). Four CBI and five CBD ponies were also hilar nerve (pulmonary vagal) denervated. Mean VE responses to hypoxia were greater in CBI ponies (delta arterial PCO2 = -4 and -7 Torr in CBI during hypoxic periods; -1 and -2 Torr in CBD). Hypoxia increased the rate of rise and mean activity of integrated diaphragm EMG in CBI (P less than 0.05) and CBD (P greater than 0.05) ponies relative to normoxia. Duration of diaphragm activity was reduced in CBI (P less than 0.05) but unchanged in CBD ponies. During hypoxia in both groups of ponies, total and mean activities per breath of transversus abdominis were reduced (P less than 0.05) without a decrease in rate of rise in activity. Time to peak and total duration of transversus abdominis activity were markedly reduced by hypoxia in CBI and CBD ponies (P less than 0.05). Hilar nerve denervation did not alter the EMG responses to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma [H+] regulation and whole blood [CO2] in exercising ponies.

The major objective was to determine in ponies whether factors in addition to changes in blood PCO2 contribute to changes in plasma [H+] during submaximal exercise. Measurements were made to establish in vivo plasma [H+] at rest and during submaximal exercise, and CO2 titration of blood was completed for both in vitro and acute in vivo conditions. In 19 ponies arterial plasma [H+] was decreased from rest 4.5 neq/l (P less than 0.05) during the 7th min of treadmill running at 6 mph, 5% grade (P less than 0.5). A 5.6-Torr exercise hypocapnia accounted for approximately 2.9 neq/l of this reduced [H+]. The non-PCO2 component of this alkalosis was approximately neq/l, and it was due presumably to a 1.7-meq/l increase from rest in the plasma strong ion difference (SID). Despite the arterial hypocapnia, mixed venous PCO2 was 2.7 Torr above rest during steady-state exercise. Nevertheless, mixed venous plasma [H+] was 1.2 neq/l above rest during exercise, which was presumably due to the increase in SID. Also studied was the effect of submaximal exercise on whole blood CO2 content (CCO2). In vitro, at a given PCO2 there was minimal difference in CCO2 between rest and exercise blood, but plasma [HCO3-] was greater for exercise blood than for rest blood. In vivo, during steady-state exercise, arterial plasma blood. In vivo, during steady-state exercise, arterial plasma [HCO3-] was unchanged or slightly elevated from rest, but CaCO2 was 4 vol% below rest.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo regulation of plasma [H+] in ponies during acute changes in PCO2.

The major objective of this study was to test the hypothesis that in ponies the change in plasma [H+] resulting from a change in PCO2 (delta H+/delta PCO2) is less under acute in vivo conditions than under in vitro conditions. Elevation of inspired CO2 and lowering of inspired O2 (causing hyperventilation) were used to respectively increase and decrease arterial PCO2 (Paco2) by 5-8 Torr from normal. Arterial and mixed venous blood were simultaneously sampled in 12 ponies during eucapnia and 5-60 min after Paco2 had changed. In vitro data were obtained by equilibrating blood in a tonometer at five different levels of PCO2. The in vitro slopes of the H+ vs. PCO2 relationships were 0.73 +/- 0.01 and 0.69 +/- 0.01 neq.1-1.Torr-1 for oxygenated and partially deoxygenated blood, respectively. These slopes were greater (P less than 0.001) than the in vivo H+ vs. PCO2 slopes of 0.61 +/- 0.03 and 0.57 +/- 0.03 for arterial and mixed venous blood, respectively. The delta HCO3-/delta pH (Slykes) was 15.4 +/- 1.1 and 17.0 +/- 1.1 for in vitro oxygenated and partially deoxygenated blood, respectively. These values were lower (P less than 0.001) than the in vivo values of 23.3 +/- 2.7 and 25.2 +/- 4.7 Slykes for arterial and mixed venous blood, respectively. In vitro, plasma strong ion difference (SID) increased 4.5 +/- 0.2 meq/l (P less than 0.001) when Pco2 was increased from 25 to 55 Torr. A 3.5-meq/l decrease in [Cl-] (P less than 0.001) and a 1.3 +/- 0.1 meq/l increase in [Na+] (P less than 0.001) accounted for the SID change.(ABSTRACT TRUNCATED AT 250 WORDS)

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)