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)     

Brain hypoxia preferentially stimulates genioglossal EMG responses to CO2

Although the dominant respiratory response to hypoxia is stimulation of breathing via the peripheral chemoreflex, brain hypoxia may inhibit respiration. We studied the effects of two levels of brain hypoxia without carotid body stimulation, produced by inhalation of CO, on ventilatory (VI) and genioglossal (EMGgg) and diaphragmatic (EMGdi) responses to CO2 rebreathing in awake, unanesthetized goats. Neither delta VI/delta PCO2 nor VI at a PCO2 of 60 Torr was significantly different between the three conditions studied (0%, 25%, and 50% carboxyhemoglobin, HbCO). There were also no significant changes in delta EMGdi/delta PCO2 or EMGdi at a PCO2 of 60 Torr during progressive brain hypoxia. In contrast, delta EMGgg/delta PCO2 and EMGgg at a PCO2 of 60 Torr were significantly increased at 50% HbCO compared with either normoxia or 25% HbCO (P less than 0.05). The PCO2 threshold at which inspiratory EMGgg appeared was also decreased at 50% HbCO (45.6 +/- 2.6 Torr) compared with normoxia (55.0 +/- 1.4 Torr, P less than 0.02) or 25% HbCO (53.4 +/- 1.6 Torr, P less than 0.02). We conclude that moderate brain hypoxia (50% HbCO) in awake, unanesthetized animals results in disproportionate augmentation of EMGgg relative to EMGdi during CO2 rebreathing. This finding is most likely due to hypoxic cortical depression with consequent withdrawal of tonic inhibition of hypoglossal inspiratory activity.     

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)     

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)     

Postnatal maturation of respiration in intact and carotid body-chemodenervated lambs

The contribution of the carotid body chemoreceptor to postnatal maturation of breathing was evaluated in lambs from 7 to 70 days of age. The study was conducted by comparing the eupneic ventilation and resting pneumograms in intact conscious lambs with those of lambs that were carotid body chemodenervated (CBD) at birth. In comparison to the 1-wk-old intact lambs, the CBD lambs had significant decreases in minute ventilation (VE, 313 vs. 517 ml/kg), tidal volume (VT, 7.2 vs. 10.5 ml/kg), respiratory rate (f, 44 vs. 51 breaths/min), and occlusion pressure (P0.1, 2.8 vs. 7.2 cmH2O). Arterial PO2's were 59 vs. 75 Torr (P less than 0.05) and arterial PCO2's 47 vs. 36 Torr (P less than 0.05), respectively, in CBD and intact lambs. In intact lambs from 7 to 70 days, resting VE decreased progressively from 517 to 274 ml/kg (P less than 0.01) due to a fall in VT, mean inspiratory flow (VT/TI), and f, whereas the ratio of inspiratory time to total breath duration remained constant. P0.1 decreased from 7.2 to 3.9 cmH2O from 7 to 42 days. In contrast the CBD lambs experienced only minimal changes in VE, VT, VT/TI, and f during the same period. VE only decreased from 313 to 218 and P0.1 from 2.8 to 2.4 cmH2O. In contrast to that of intact lambs the resting pneumogram of CBD lambs remained relatively fixed from 7 to 70 days. Three CBD lambs died unexpectedly, without apparent cause, in the 4th and 5th wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperventilation in ponies at the onset of and during steady-state exercise

We studied blood gases in ponies to assess the relationship of alveolar ventilation (VA) to pulmonary CO2 delivery during moderate treadmill exercise. In normal ponies for 1.8, 3, or 6 mph, respectively, partial pressure of CO2 in arterial blood (PaCO2) decreased maximally by 3.1, 4.4, and 5.7 Torr at 30-90 s of exercise and remained below rest by 1.4, 2.3, and 4.5 Torr during steady-state (4-8 min) exercise (P less than 0.01). Partial pressure of O2 in arterial blood (PaO2) and arterial pH, (pHa) also reflected hyperventilation. Mixed venus CO2 partial pressure (PVCO2) decreased 2.3 and 2.9 Torr by 30 s for 3 and 6 mph, respectively (P less than 0.05). In work transitions either from 1.8 to 6 mph or from 6 mph to 1.8 mph, respectively, PaCO2 either decreased 3.8 Torr or increased 3.3 Torr by 45 s of the second work load (P less than 0.01). During exercise in acute (2-4 wk) carotid body denervated (CBD) ponies at 1.8, 3, or 6 mph, respectively, PaCO2 decreased maximally below rest by 9.0, 7.6, and 13.2 Torr at 30-45 s of exercise and remained below rest by 1.3, 2.3, and 7.8 Torr during steady-state (4-8 min) exercise (P less than 0.1). In the chronic (1-2 yr) CBD ponies, the hypocapnia was generally greater than normal but less than in the acute CBD ponies. We conclude that in the pony 1) VA is not tightly matched to pulmonary CO2 delivery during exercise, particularly during transitional states, 2) the exercise hyperpnea is not mediated by PaCO2 or PVCO2, and 3) during transitional states in the normal pony, the carotid bodies attenuate VA drive thereby reducing arterial hypocapnia.     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

Endogenous opioid effects on abdominal muscle activity during inspiratory loading

In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l-1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Ventilatory control in peripheral chemoreceptor-denervated ponies during chronic hypoxemia.

The present study was designed to provide further insight into the role of the carotid and aortic chemoreceptors in ventilatory (VE) acclimatization during sojourn at altitude. Measurements were made: 1) on 10 ponies near sea level (SL, 740 Torr) under normal conditions, 2) on 6 of these at SL following chemoreceptor denervation (CD), and 3) subsequently on all 10 during 4 days of hypobaric hypoxia (PaO2 = 40-47 Torr). CD resulteo in hypoventilation at SL (deltaPaCO2 = d8 Torr, P less than 0.05), and it prevented hyperventilation normally observed with injection of NaCN and acute exposure to hypoxia (less than 1 h). In contrast, hyperventilation was evident in normal ponies during acute hypoxia (deltaPaCO2 = -6.7 Torr). Ventilation increased in both groups between the 2nd and 8th h of hypoxia (deltaPaCO2 from 1 h = -4 Torr, P less than 0.05). This change, a common characteristic of acclimatization, persisted throughout 4 days of hypoxia in the normal ponies. However, in the CD ponies this change was evident consistently only through the 12th h and after the 44 h hyperventilation was no longer evident. We conclude that the peripheral chemoreceptors are essential in ponies for normal VE acclimatization to this degree of hypoxemia. Two additional findings in CD ponies suggest the presence of a CNS inhibitory influence on the VE control center during chronic hypoxemia. First, acute hyperoxygenation on the 4th day of hypoxemia induced hyperventilation (deltaPaCO2 = -5 Torr, P less than 0.05). Second, again on the 4th day and during hyperoxygenation, VE responsiveness to CO2 and doxapram HCl was greater than at sea level.     

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 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.     

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.     

No effect of brain blood flow on ventilatory depression during sustained hypoxia

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10-25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9-21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(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)     

Carotid bodies are required for ventilatory acclimatization to chronic hypoxia

We have compared the ventilatory responses of intact and carotid body-denervated (CBD) goats to moderate [partial pressure of O2 in arterial blood; (Pao2) approximately 44 Torr] and severe (Pao2 approximately 33 Torr) many time points for up to 7 days of hypobaria. In the intact group there were significant time-dependent decreases in partial pressure of CO2 in arterial blood (PaCO2) in both moderate and severe hypoxemia (approximately-7 and -11 Torr) that were largely complete by 8 h of hypoxemia and maintained throughout. Acute restoration of normoxia in chronically hypoxic intact animals produced time-dependent increases in Paco2 over 2 h, but hypocapnia persisted relative to sea-level control. Arterial plasma [HCO3-] and [H+] decreased, and [Cl-] increased with a time course and magnitude consistent with developing hypocapnia. Chronic CBD, per se, resulted in a sustained, partially compensated respiratory acidosis, as PaCO2 rose 6 Torr and base excess rose 3 mEq/1, [Cl-] fell 1 mEq/1, and pHa fell 0.01 units. During exposure to identical levels of arterial hypoxemia as in the intact group. CBD animals showed no significant changes in PaCO2, [H+]a, or [HCO3-]a at any time during moderate or severe hypoxemia. Plasma [C1-] remained within the normal range throughout exposure to moderate hypoxia and increased in severe hypoxia. In a few instances some hypocapnia was observed, but this was highly inconsistent and was always less than one-third of that observed in intact goats. In contrast to intact goats, acute restorations of normoxia in the chronically hypoxic CBD goats always caused hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of uncompensated and compensated metabolic acidosis on canine diaphragm

We investigated the effects of metabolic acidosis and compensated metabolic acidosis on force of contraction of the diaphragm in anesthetized dogs. Mechanically ventilated animals were prepared with an open thorax. A balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi), and a plaster cast was placed around the abdomen to maintain length and geometry of the diaphragm. The force of contraction was evaluated by measuring Pdi during supramaximal phrenic stimulation at different frequencies and also during spontaneous inspiratory efforts. In 13 dogs with an arterial pH (pHa) of 7.38 and arterial PCO2 (PaCO2) of 36.5 Torr, metabolic acidosis was produced by infusion of HCl until pHa equaled 6.98 and PaCO2 equaled 36.4 Torr. Pdi at all frequencies greater than 10 Hz was significantly reduced (P less than 0.05). The dogs were then hyperventilated until pHa was 7.34 and PaCO2 was 12.8 Torr. Pdi was significantly reduced again at all frequencies (P less than 0.05) except 5 Hz. The percent reduction in Pdi by compensated acidosis was significantly greater at low-frequency stimulation than at high (P less than 0.05). Similar qualitative results were observed during spontaneous inspiratory efforts where Pdi was compared at constant magnitudes of diaphragmatic electromyograms. Twitch characteristics revealed that metabolic acidosis led to a significant shortening of twitch relaxation time (P less than 0.05), and compensated metabolic acidosis added to this effect a significant decrease in twitch amplitude (P less than 0.05).     

Changes in breathing when switching from nares to tracheostomy breathing in awake ponies

We assessed the consequences of respiratory unloading associated with tracheostomy breathing (TBr). Three normal and three carotid body-denervated (CBD) ponies were prepared with chronic tracheostomies that at rest reduced physiological dead space (VD) from 483 +/- 60 to 255 +/- 30 ml and lung resistance from 1.5 +/- 0.14 to 0.5 +/- 0.07 cmH2O . l-1 . s. At rest and during steady-state mild-to-heavy exercise arterial PCO2 (PaCO2) was approximately 1 Torr higher during nares breathing (NBr) than during TBr. Pulmonary ventilation and tidal volume (VT) were greater and alveolar ventilation was less during NBr than TBr. Breathing frequency (f) did not differ between NBr and TBr at rest, but f during exercise was greater during TBr than during NBr. These responses did not differ between normal and CBD ponies. We also assessed the consequences of increasing external VD (300 ml) and resistance (R, 0.3 cmH2O . l-1 . s) by breathing through a tube. At rest and during mild exercise tube breathing caused PaCO2 to transiently increase 2-3 Torr, but 3-5 min later PaCO2 usually was within 1 Torr of control. Tube breathing did not cause f to change. When external R was increased 1 cmH2O . l-1 . s by breathing through a conventional air collection system, f did not change at rest, but during exercise f was lower than during unencumbered breathing. These responses did not differ between normal, CBD, and hilar nerve-denervated ponies, and they did not differ when external VD or R were added at either the nares or tracheostomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Presynaptic regulation of cardiac sympathetic function in hypoxic guinea pigs

In the normal heart, presynaptic cholinergic muscarinic and alpha 2-adrenergic mechanisms modify the fractional rate constant for norepinephrine (NE) synthesis (kNE), an index of sympathetic neural function. To evaluate presynaptic regulation of kNE, conscious guinea pigs subjected to normoxia and then hypoxia (n = 7-8 in each group) were pretreated with 1) vehicle; 2) a cholinergic muscarinic antagonist, methyl atropine; 3) an alpha 2-antagonist, yohimbine; or 4) a combination of the two. An increase of kNE was determined from incorporation of radiolabeled tyrosine into NE in a control period (arterial PO2 130 +/- 1.7 Torr, PCO2 36 +/- 0.5 Torr) and during a hypoxic state (PO2 49.6 +/- 1.0 Torr, PCO2 36 +/- 0.5 Torr). Hypoxia activated kNE in the atrioventricular node and right ventricular moderator band in vehicle-treated animals (P less than 0.05). Sympathetic activation was more general, however, because alpha 2-presynaptic influence acted to limit kNE in all tissues tested (P less than 0.05) except muscle, spleen, and posterior left ventricle. Cholinergic muscarinic presynaptic restraint on kNE was detected during hypoxia only in the left atrial appendage and lung (P less than 0.05). These data indicate that hypoxia increases kNE in the heart, but restraint by cholinergic muscarinic and alpha 2-adrenergic presynaptic mechanisms limits increases in neurotransmitter synthesis and noradrenergic activation regionally.     

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)