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)     

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.     

Cardiac receptors evoke ventilatory response with increased venous PCO2 at constant arterial PCO2

The effects of elevated venous PCO2 and denervation of the cardiac ventricles on ventilation were studied in 20 anesthetized open-chest unidirectionally ventilated White Leghorn cockerels. Venous PCO2 was increased by insufflating the gut with high CO2 while recording changes in the amplitude of the sternal movements. Arterial blood gases were held constant by unidirectionally ventilating the lungs with gas flows approximately five times the animal's resting minute volume. Insufflating the gut with 90% N2-10% O2 did not change the level of ventilation, whereas with 90% CO2-10% O2 the amplitude of sternal movement increased 500% above that with no gut gas flow. Exchange of N2 for the CO2 was followed by a rapid reduction of ventilatory movements to control levels. Arterial blood gases remained constant during gut gas insufflation, whereas mixed venous PCO2 increased and mixed venous pH decreased when high CO2 was given to the gut. Cutting the middle cardiac nerves, which primarily innervate the ventricles of the heart, reduced the ventilatory response to CO2 gut insufflation by 67%. Sympathetic denervation of the thoracic viscera did not change the responses. It appears that, in the chicken, increasing the mixed venous PCO2 while holding the arterial blood gases constant alters ventilation by an afferent system located in the venous circulation or in the right ventricle which is sensitive to changes in PCO2.     

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

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

Effect of pulmonary arterial PCO2 on breathing pattern

We studied breathing patterns and tidal volume (VT)-inspiratory time (TI) relationships at three steady-state levels of pulmonary arterial PCO2 (PpCO2) in 10 anesthetized dogs. To accomplish this we isolated and then separately pump perfused the pulmonary and systemic circulations, which allowed us to control blood gases in each circuit independently. To ventilate the lungs at a rate and depth determined by central drive, we used an electronically controlled positive-pressure ventilator driven by inspiratory phrenic neural activity. Expiratory time (TE) varied inversely with PpCO2 over the range of PpCO2 from approximately 20 to 80 Torr. VT and TI increased with rising PpCO2 over the range from approximately 20 to 45 Torr but did not change further as PpCO2 was raised above the middle level of approximately 45 Torr. Thus minute ventilation increased as a function of TE and VT as PpCO2 was increased over the lower range and increased solely as a function of TE as PpCO2 was increased over the upper range. The VT-TI relationship shifted leftward on the time axis as PpCO2 was lowered below the middle level but did not shift in the opposite direction as PpCO2 was raised above the middle level. In addition to its effect on breathing pattern, we found that pulmonary hypocapnia depressed inspiratory drive.     

Gas-blood PCO2 gradients during avian gas exchange.

The avian respiratory system is a crosscurrent gas exchange system. One of the aspects of this type of gas exchange system is that end-expired PCO2 is greater than arterial PCO2, the highest possible value being equal to mixed venous PCO2. We made steady-state measurements of arterial, mixed venous, and end-expired PCO2 in anesthetized, spontaneously breathing chickens during inhalation of room air or 4-8% CO2. We found end-expired PCO2 to be higher than both arterial and mixed venous PCO2, the sign of the differences being such as to oppose passive diffusion. The observation that end-expired PCO2 was higher than arterial PCO2 can be explained on the basis of crosscurrent gas exchange. However, the observation that end-expired PCO2 exceeded mixed venous PCO2 must be accounted for by some other mechanism. The positive end-expired to mixed venous PCO2 gradients can be explained if it is postulated that the charged membrane mechanism suggested by Gurtner et al. (Respiration Physiol. 7: 173-187, 1969) is present in the avian lung.     

Metabolic component of intestinal PCO(2) during dysoxia.

The adequacy of intestinal perfusion during shock and resuscitation might be estimated from intestinal tissue acid-base balance. We examined this idea from the perspective of conventional blood acid-base physicochemistry. As the O(2) supply diminishes with failing blood flow, tissue acid-base changes are first "respiratory, " with CO(2) coming from combustion of fuel and stagnating in the decreasing blood flow. When the O(2) supply decreases to critical, the changes become "metabolic" due to lactic acid. In blood, the respiratory vs. metabolic distinction is conventionally made using the buffer base principle, in which buffer base is the sum of HCO(3)(-) and noncarbonate buffer anion (A(-)). During purely respiratory acidosis, buffer base stays constant because HCO(3)(-) cannot buffer its own progenitor, carbonic acid, so that the rise of HCO(3)(-) equals the fall of A(-). During anaerobic "metabolism," however, lactate's H(+) is buffered by both A(-) and HCO(3)(-), causing buffer base to decrease. We quantified the partitioning of lactate's H(+) between HCO(3)(-) and A(-) buffer in anoxic intestine by compressing intestinal segments of anesthetized swine into a steel pipe and measuring PCO(2) and lactate at 5- to 10-min intervals. Their rises followed first-order kinetics, yielding k = 0. 031 min(-1) and half time = approximately 22 min. PCO(2) vs. lactate relations were linear. Over 3 h, lactate increased by 31 +/- 3 mmol/l tissue fluid (mM) and PCO(2) by approximately 17 mM, meaning that one-half of lactate's H(+) was buffered by tissue HCO(3)(-) and one-half by A(-). The data were consistent with a lumped pK(a) value near 6.1 and total A(-) concentration of approximately 30 mmol/kg. We conclude that the respiratory vs. metabolic distinction could be made in tissue by estimating tissue buffer base from measured pH and PCO(2).     

Entrainment of respiratory rhythm to respiratory oscillations of arterial PCO2 in vagotomized dogs.

The aim of this study was to demonstrate that the medullary respiratory rhythm generator is capable of entraining to respiratory oscillations of arterial PCO2 (CO2 oscillations). We used 10 anesthetized, paralyzed, vagotomized, and mechanically ventilated dogs. First, rate of mechanical ventilation was manually adjusted so that it matched the dog's spontaneous respiratory rate, which established a constant phase relationship between the mechanical ventilation and the burst of phrenic neurogram (initial phase). Then this phase relationship was temporally disturbed by a brief electrical stimulation of the superior laryngeal nerve (SLN). In the control group, the initial phase and the steady-state phase relationship after SLN stimulation were randomly distributed within the phase plane, implying no interaction between the respiratory center and mechanical ventilation. In contrast, when CO2 output from the lung was increased 2.6-fold above the control level by venous CO2 loading, the initial phase and the steady-state phase after SLN stimulation were locked in such a way that the onset of the burst of phrenic neurogram coincided with the peak of CO2 oscillations. This was not demonstrated when the dog was made hyperoxic. We therefore conclude that the respiratory center could entrain to phasic chemical afferent inputs originating from CO2 oscillations, provided they are considerably amplified.     

Respiratory muscle function during CO2 rebreathing with inspiratory flow-resistive loading

We investigated the respiratory muscle contribution to inspiratory load compensation by measuring diaphragmatic and intercostal electromyograms (EMGdi and EMGic), transdiaphragmatic pressure (Pdi), and thoracoabdominal motion during CO2 rebreathing with and without 15 cmH2O X l-1 X s inspiratory flow resistance (IRL) in normal sitting volunteers. During IRL compared with control, Pdi measured during airflow and during airway occlusion increased for a given change in CO2 partial pressure and EMGdi, and there was a greater decrease in abdominal (AB) end expiratory anteroposterior dimensions with increased expiratory gastric pressure (Pga), this leading to an inspiratory decline in Pga with outward AB movement, indicating a passive component to the descent of the abdomen-diaphragm. The response of EMGic to IRL was similar to that of EMGdi, though rib cage (RC)-Pga plots did infer intercostal muscle contribution. We conclude that during CO2 rebreathing with IRL there is improved diaphragmatic neuromuscular coupling, the prolongation of inspiration promoting a force-velocity advantage, and increased AB action serving to optimize diaphragm length and configuration, as well as to provide its own passive inspiratory action. Intercostal action provides increased assistance also. Therefore, compensation for inspiratory resistive loads results from the combined and integrated effort of all respiratory muscle groups.     

Cerebral blood flow during orthostasis: role of arterial CO2

Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and their relation to increases in alveolar ventilation (Va) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/- 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased Va but could be due to ventilation-perfusion mismatch or a redistribution of CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.