Comparison of ventilatory responses to sustained reduction in arterial oxygen tension vs. content in awake ponies.

To gain insight into central and peripheral contributions to changes in breathing during hypoxia, we compared effects on breathing of reducing inspired PO2 (hypoxic hypoxia) with reducing arterial O2 content (CaO2) through elevation of carboxy-hemoglobin (COHb) (CO hypoxia). Twelve awake ponies were studied during 1 h of breathing room air followed by 6 h when COHb was increased to 25% and CaO2 was decreased by 17%. When COHb was increased, arterial PCO2 (PaCO2) increased gradually to 1.3 Torr above (P < 0.05) control level between 30 and 45 min of CO exposure. Pulmonary ventilation (VE) decreased (P = 0.09) approximately 1 liter the first 30 min of CO exposure. After approximately 45 min, PaCO2 began to decrease, steadily reaching 1.5 Torr below (P < 0.05) control level by 4.5 h of CO hypoxia. VE did not change significantly after 30 min of elevated COHb. Eight ponies were also studied during 5 h of hypoxic hypoxia (arterial PO2 approximately 40 Torr). PaCO2 decreased 5 Torr (P < 0.05) within 5 min of hypoxia and decreased another 4 Torr (P < 0.05) between 30 min and 5 h of hypoxia consistent with hypoxic ventilatory acclimatization. VE increased (P < 0.05) within 3 min of hypoxic hypoxia but then decreased (P < 0.05; VE roll off) toward control and did not increase significantly with acclimatization. Because CO and hypoxic hypoxia both decrease brain oxygenation but only hypoxic hypoxia increases carotid chemoreceptor activity, we conclude that initial hypoventilation with CO hypoxia and VE roll off with hypoxic hypoxia are consistent with hypoxic ventilatory depression within the brain. In addition, hyperventilation with prolonged CO hypoxia is consistent with a central nervous system mechanism contributing to this phase of hypoxic ventilatory acclimatization in ponies.

Breathing periodicity in intact and carotid body-denervated ponies during normoxia and chronic hypoxia.

Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063-0.500 cycles/breath were observed in all parameters during both normoxia and hypoxia. During normoxia, CBD accentuated periodicity of VT (P < 0.02) and VI (P < 0.01) but did not change TI or TE periodicity (P > 0.05). These findings suggest that carotid chemoreceptors serve to stabilize breathing (i.e., decrease periodicity) during normoxia, conceivably because of their shorter response time compared with that of central chemoreceptors. During certain periods of hypoxia, periodicity of VT and VI was significantly (P < 0.05) increased in intact ponies. The response to hypoxia in CBD ponies was variable, with VI periodicity significantly (P < 0.05) increasing, decreasing, or unchanging. Because some CBD ponies significantly changed their periodicity during hypoxia compared with normoxia, we conclude that carotid chemoreceptors are not requisite for hypoxia-induced changes in periodic breathing. In addition, our observations in both groups of ponies during normoxia and hypoxia suggest that multiple mechanisms may lead to periodic oscillations in breathing.

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)

Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats.

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.

Effect of hypoxia on metabolic rate in awake ponies.

To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobin, arterial PCO2 was 1.3 Torr above (P < 0.05) and 1.5 Torr (P < 0.05) below control levels after 30 min and 3 h, respectively. There were no significant (P > 0.10) changes in VO2 during either hypoxic or CO hypoxia. However, in 50% of the ponies, VO2, pulmonary ventilation, and rectal temperature increased and shivering was evident after 30 min of hypoxia. Peak values of pulmonary ventilation, VO2, and shivering occurred at approximately 2 h with a subsequent return toward control levels. We conclude that, in contrast to smaller mammals, acute hypoxia does not depress VO2 of ponies. The hypermetabolism and hyperthermia during chronic hypoxia in some ponies may reflect a transient failure in thermoregulation.

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)

Independence of exercise hyperpnea and acidosis during high-intensity exercise in ponies.

We investigated arterial PCO2 (PaCO2) and pH (pHa) responses in ponies during 6-min periods of high-intensity treadmill exercise. Seven normal, seven carotid body-denervated (2 wk-4 yr) (CBD), and five chronic (1-2 yr) lung (hilar nerve)-denervated (HND) ponies were studied during three levels of constant load exercise (7 mph-11%, 7 mph-16%, and 7 mph-22% grade). Mean pHa for each group of ponies became alkaline in the first 60 s (between 7.45 and 7.52) (P less than 0.05) at all work loads. At 6 min pHa was at or above rest at 7 mph-11%, moderately acidic at 7 mph-16% (7.32-7.35), and markedly acidic at 7 mph-22% (7.20-7.27) for all groups of ponies. Yet with no arterial acidosis at 7 mph 11%, normal ponies decreased PaCO2 below rest (delta PaCO2) by 5.9 Torr at 90 s and 7.8 Torr by 6 min of exercise (P less than 0.05). With a progressively more acid pHa at the two higher work loads in normal ponies, delta PaCO2 was 7.3 and 7.8 Torr by 90 s and 9.9 and 11.4 Torr by 6 min, respectively (P less than 0.05). CBD ponies became more hypocapnic than the normal group at 90 s (P less than 0.01) and tended to have greater delta PaCO2 at 6 min. The delta PaCO2 responses in normal and HND ponies were not significantly different (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats.

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60-100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

Effects on breathing of ventrolateral medullary cooling in awake goats.

Our objective was to investigate the role of the ventrolateral medulla (VLM) in the control of breathing during the awake state. In 17 awake adult goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of the area between the first hypoglossal rootlet and the ponto-medullary junction (so-called area M (rostral) and area S). Within 5 s after the initiation of cooling, 60-100% of areas M and S, pulmonary ventilation (VE) decreased uniformly over conditions of eucapnia, hypercapnia, hypoxia, and exercise (P < 0.05). Between 10 and 20 s of cooling, the reduction in VE was approximately 10% greater during eucapnia and hypercapnia than during hypoxia and exercise (P < 0.05). For the remaining 10 s of cooling and for about 1 min after cooling, VE increased to and above control level. Cooling only rostral area M or only caudal area M-rostral area S affected breathing qualitatively in the same manner as when 60-100% of areas M and S were cooled. However, cooling caudal area S had effects that differed significantly (P < 0.05) from more rostral cooling in that the initial decrease in VE was attenuated and the subsequent increase was accentuated. The initial uniform decreased VE during cooling suggests that superficial VLM nonchemoreceptor neurons facilitate breathing. The subsequent relatively greater effect of cooling during eucapnia and hypercapnia probably reflects dysfunction of chemoreceptor-related neurons that normally stimulate breathing. The stimulation of breathing during the later stages and after cooling may suggest that some VLM neurons inhibit breathing.

Changes in respiratory muscle activity in ponies when end-expiratory lung volume is increased.

The objective of the present study was to determine whether lung and diaphragm afferents contribute to the changes in respiratory muscle activity when end-expiratory lung volume (EELV) is changed in ponies. We studied the responses of the diaphragm and the transversus abdominis (TA) muscles to passive increases in EELV in awake intact (I), diaphragm-deafferented (DD), pulmonary vagal- (hilar nerve) denervated (HND), and DD + HND ponies. Negative pressure of -10 or -20 cmH2O applied around the ponies' torsos [positive transrespiratory (TR) pressure] increased (P < 0.05) EELV in all ponies; the increases were more (P < 0.05) in HND and less (P < 0.05) in DD than in I ponies. In I ponies, positive TR pressure increased (P < 0.05) the rate of rise of the integrated diaphragmatic electromyogram (EMG), reflecting increased drive to the muscle. This increase was less (P < 0.05) in DD and HND than in I ponies. In DD + HND ponies, there was no significant (P > 0.10) change in drive to the diaphragm during positive TR pressure. In I ponies, positive TR pressure increased (P < 0.05) the duration and mean activity of the TA EMG. In HND and DD + HND ponies, the TA EMG was not altered by positive TR pressure. I and DD ponies decreased (P < 0.05) breathing frequency but maintained tidal volume (VT) during positive TR pressure. HND and DD+HND ponies increased breathing frequency (P < 0.05) and decreased (P < 0.05) VT during positive TR pressure. We conclude that, during positive TR pressure when the diaphragm is presumably at a mechanical disadvantage, diaphragm and vagal afferents mediate increased drive to the diaphragm to prevent VT from decreasing. In addition, during positive TR pressure, vagal afferents mediate an increase in duration of TA activity, which minimizes the increase in EELV.

Diaphragm and lung afferents contribute to inspiratory load compensation in awake ponies.

We determined the effect of pulmonary vagal (hilar nerve) denervation (HND) and diaphragm deafferentation (DD) on inspiratory load compensation. We studied awake intact (I; n = 10), DD (n = 5), HND (n = 4), and DD+HND (n = 7) ponies at rest and during mild (1.8 mph, 5% grade) and moderate (1.8 mph, 15% grade) treadmill exercise before, during, and after resistance of the inspiratory circuit was increased from approximately 1.5 to approximately 20 cmH2O.l-1.s. During the first loaded breath in I ponies at rest, inspiratory time (TI) increased, expiratory time decreased, and inspiratory drive increased. There were minimal changes after the first breath, and inspiratory minute ventilation (VI) and arterial PCO2 did not change (P > 0.10) from control values. On the first loaded breath during exercise, TI increased but inspiratory drive either did not change or decreased from control values. TI and drive increased after the first breath, but the increases were insufficient to maintain VI and arterial PCO2 at control levels. First-breath load compensation remained after DD, HND, and DD+HND, but after DD+HND tidal volume and VI were compensated 5-10% less (P < 0.05) than in I ponies. In all groups inspiratory drive, tidal volume, and VI were markedly augmented on the first breath after loading was terminated with a gradual return toward control. We conclude that diaphragm and pulmonary afferents contribute to but are not essential for inspiratory load compensation in awake ponies.

Effect of asthma and ventilatory loading on arterial PCO2 of humans during submaximal exercise.

In humans, attenuating carotid chemoreceptor activity by hyperoxia does not alter arterial PCO2 (PaCO2) during submaximal exercise, yet a transient hypercapnia occurs in carotid chemoreceptor-resected (CBR) asthmatic subjects during submaximal exercise. We hypothesized that this difference was due to asthma and not CBR causing the abnormal response. Accordingly, we determined the temporal pattern of PaCO2 during mild and moderate exercise in chemoreceptor-intact asthmatic (n = 10) and nonasthmatic subjects (n = 10). We also hypothesized that hyperoxia alters PaCO2 during exercise if exercise already has disrupted PaCO2 homeostasis. Accordingly, we studied, during exercise, asthmatic subjects while hyperoxic; nonasthmatic subjects during loaded breathing of room air, which increased PaCO2; and nonasthmatic subjects during loaded breathing while hyperoxic. While breathing room air, neither asthmatic nor nonasthmatic subjects maintained arterial isocapnia during exercise. An increase in PaCO2 between rest and exercise and between mild exercise and 1st min of moderate exercise was greater in asthmatic than in nonasthmatic subjects (P < 0.05). In six asthmatic subjects that were hypercapnic breathing room air during exercise, hypercapnia was accentuated by hyperoxia. The ventilatory load in nonasthmatic subjects resulted in a work load-dependent hypercapnia (P < 0.01) accentuated (P < 0.01) by hyperoxia. We conclude that normally in humans the carotid chemoreceptors contribute minimally to the hyperpnea of submaximal exercise. However, when PaCO2 is increased from resting values during exercise, then the chemoreceptors serve to augment ventilation and thereby minimize the hypercapnia.

Effect of cardiac denervation on cardiorespiratory responses to exercise in goats.

The purpose of this study was to determine whether intact cardiac innervation and a normal cardiovascular (CV) response are required for a normal ventilatory (VE) response to mild and moderate treadmill exercise in awake goats. Accordingly, we measured CV and respiratory responses to two levels of exercise in seven normal (N) and six cardiac-denervated (CD) goats. Evidence of surgical CD included 1) absence of a cardiac response during surgery when the left thoracic cardiac nerves, thoracic vagi, and right and left stellate ganglia were electrically stimulated, 2) total and 80% attenuation of baroreflex changes in heart rate (HR) when arterial blood pressure was raised or lowered, respectively, by infusion of vasoactive agents in awake goats, and 3) attenuation of the CV responses to exercise. At each level of exercise in the CD goats, the HR response was significantly reduced relative to the response observed before CD (P less than 0.05) and the recovery HR response was delayed. Cardiac index increased in a work rate-dependent manner in N and CD goats but was significantly lower in the CD animals (P less than 0.05). Hypotension was consistently observed during exercise following CD. There was no effect of CD on steady-state VE at any metabolic rate or on the VE-O2 uptake relationship (P greater than 0.05). The rest-to-work and work-to-work transition responses of arterial PCO2 were similar between N and CD goats, but there was a tendency toward greater hypocapnia at the exercise onset in CD goats at the highest work rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of increased end-expiratory lung volume on breathing in awake ponies.

We studied the changes in breathing and respiratory muscle electromyograms (EMG) during passively induced increases in end-expiratory lung volume (EELV) in awake normal (N), hilar nerve-denervated (HND), carotid body-denervated (CBD), and HND + CBD ponies. EELV was increased by applying continuous negative pressure (-10 and -20 cmH2O) around the torso of the standing pony. In all groups, negative pressure produced sustained increases in EELV that were linearly related to the degree of negative pressure. Elevated EELV decreased breathing frequency (f) in N and CBD ponies but increased f in HND and HND + CBD ponies. When EELV was increased, tidal volume was unchanged or above control in N ponies but was below or near control in the other groups. In all groups during elevated EELV, arterial PCO2 initially decreased but then increased relative to control with isocapnia achieved after approximately 1.5 min. In all groups, the elevated EELV was accompanied by increased stimulation of the diaphragm as indicated by increased rate of rise of the integrated EMG (P less than 0.05). During elevated EELV, the duration of diaphragm EMG was reduced, but only in HND ponies was this reduction significant (P less than 0.05). In N ponies, the major effect of elevated EELV on the expiratory transversus abdominis (TA) muscle was an increase (P less than 0.05) in duration of activity and therefore total activity. The work of breathing was thus presumably shifted more to this muscle during elevated EELV. These changes in TA timing were not observed in HND and HND + CBD ponies during elevated EELV. We conclude that elevation of EELV, which presumably places the diaphragm on a less favorable portion of its length-tension relationship, results in compensatory increased stimulation of the diaphragm that is not critically dependent on hilar and carotid chemoreceptor afferents. However, hilar afferents do contribute to the changes in diaphragm and TA duration of activity during elevated EELV.

Effect of increased inspired CO2 on respiratory dead space in ponies.

The objective of the present study was to determine the effect of elevated inspired CO2 on respiratory dead space (VD) of 12 normal, 8 carotid body-denervated (CBD), 7 hilar nerve-denervated (HND), and 6 CBD+HND ponies. The Fowler technique was used to determine VD on a breath-by-breath basis while the ponies breathed room air and inspired CO2 at 3 and 6%. During room air breathing, tidal volume (VT) and VD were greater in HND ponies than in normal and CBD ponies (P less than 0.05), and VT was less and VD/VT was greater after CBD than before CBD. For all groups. VD, VT, and breathing frequency (f) increased and VD/VT decreased significantly (P less than 0.01) with increasing inspired CO2. During CO2 breathing, VT and VD were higher (P less than 0.05) in the HND ponies than in all other groups, the decrease (P less than 0.05) in VD/VT was greatest in the CBD+HND group, and f was lower in the HND and HND+CBD than in the normal and CBD ponies. In addition, when inspired CO2 was increased from 0 to 6%, the decrease in VD/VT was greater and the increase in arterial PCO2 was less (P less than 0.05) after CBD than before CBD. For 70% of the ponies in all groups, VD increased linearly with increases in VT; for most of the remainder, VD tended to plateau at higher values of VT.

Ventilatory compensation for lactacidosis in ponies: role of carotid chemoreceptors and lung afferents.

We investigated changes in arterial PCO2 (PaCO2) and pulmonary ventilation (VE) in normal, carotid chemoreceptor-denervated, and hilar nerve-denervated ponies during intravenous lactic acid infusion at rest and treadmill exercise at 1.8 mph-5% grade (mild) and 1.8 mph-15% grade (moderate). Lactic acid, (0.5 M) infusion of 0.10, 0.13, and 0.20 ml.min-1.kg-1 at rest and mild and moderate exercise increased arterial [H+] linearly throughout the 10 min of acid infusion. At 10 min of infusion, arterial [H+] had increased approximately 20 nmol/l (0.2 pH units) for each condition and group. Under most conditions, the temporal pattern of PaCO2 during acid infusion was biphasic. At rest and during mild exercise in all groups, and in carotid chemoreceptor-denervated ponies during moderate exercise, PaCO2 increased approximately 2 Torr (P less than 0.05) during the first 2 min of acid infusion. However, in normal ponies during moderate exercise, PaCO2 was not changed from control in the first 2 min of infusion. Between 2 and 10 min of infusion at rest and mild and moderate exercise in all groups, there was a 5-Torr significant decrease in PaCO2, which did not differ (P greater than 0.10) between groups. VE increased between 15-30 s and 2 min of infusion, but VE changed minimally between 2 and 10 min of infusion at rest and exercise in all groups of ponies. We conclude that lactacidosis does increase VE at rest and submaximal exercise in the pony.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic hypoxia on breathing and EMGs of respiratory muscles in awake ponies.

Breathing, diaphragmatic and transversus abdominis electromyograms (EMGdi and EMGta, respectively), and arterial blood gases were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in intact (n = 11) and carotid body-denervated (CBD, n = 9) awake ponies. In intact ponies, arterial PCO2 was 7, 5, 9, and 11 Torr below control (P less than 0.01) at 1 and 10 min and 5 and 24-48 h of hypoxia, respectively. In CBD ponies, arterial PCO2 was 3-4 Torr below control (P less than 0.01) at 4, 5, 6, and 24 h of hypoxia. In intact ponies, pulmonary ventilation, mean inspiratory flow rate, and rate of rise of EMGdi and EMGta changed in a multi-phasic fashion during hypoxia; each reached a maximum during the 1st h (P less than 0.05), declined between 1 and 5 h (P less than 0.05), and increased between 5 and 24-48 h of hypoxia. As a result of the increased drive to the diaphragm, the mean EMGdi was above control throughout hypoxia (P less than 0.05). In contrast, as a result of a sustained reduction in duration of the EMGta, the mean EMGta was below control for most of the hypoxic period. In CBD ponies, pulmonary ventilation and mean inspiratory flow rate did not change during chronic hypoxia (P greater than 0.10). In these ponies, the rate of rise of the EMGdi was less than control (P less than 0.05) for most of the hypoxic period, which resulted in the mean EMGdi to also be less than control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)