CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.     

Fluorescence location of RVLM kainate microinjections that alter the control of breathing

Kainic acid (4.7 mM) applied to the rostral ventrolateral medulla (RVLM) surface decreases phrenic output, CO2 sensitivity, and blood pressure in chloralose-urethan-anesthetized, vagotomized, paralyzed, glomectomized, servoventilated cats. In this study using the same preparation, bilateral 50- to 100-nl kainate injections just below the RVLM surface better localized these responses topographically. The physiological responses to unilateral 10-nl kainate injections were then correlated with anatomic location determined by fluorescent microbeads (0.5 micron diam). Many sites were associated with no effect, a few rostral and caudal sites with increased phrenic activity, and cluster of sites with decreased phrenic activity often to apnea, decreased CO2 sensitivity, and decreased responses to carotid sinus nerve stimulation. Blood pressure was unaffected. These sites, within 400 microns of the surface, were ventral to the facial nucleus, ventrolateral to the nucleus paragigantocellularis lateralis, caudal to the superior olive, and rostral to the retrofacial nucleus. They appeared to be within the recently described retrotrapezoid nucleus, which contains cells with respiratory-related activity and projections to the dorsal and ventral respiratory groups. Cells within this site appear able to provide tonic input to respiration and to affect peripheral and central chemoreception.     

Recovery from central apnea: effect of stimulus duration and end-tidal CO2 partial pressure

The present study was designed to investigate the effect of stimulus duration and chemosensory input on the recovery of central respiratory activity from apnea induced by superior laryngeal nerve (SLN) electrical stimulation. Newborn piglets less than 8 days of age were anesthetized, paralyzed, and mechanically ventilated at differing levels of end-tidal CO2 partial pressure (PCO2). The vagi were cut bilaterally in the neck. Integrated phrenic nerve activity was used as the index of respiratory activity. SLN stimulation caused apnea that persisted after stimulus cessation. The length of apnea following stimulus cessation was directly related to stimulus duration and inversely related to end-tidal PCO2. After apnea, respiratory activity returned gradually to the initial control level. The recovery pattern was well described by a linear regression function using the natural logarithm of time as the independent variable. Prolonging stimulus duration progressively inhibited the amount of initial respiratory activity following apnea. On the other hand, the rate of respiratory recovery was independent of stimulus duration and, except at low end-tidal PCO2 following long (30 s) stimuli, was independent of the end-tidal PCO2 level. These results demonstrate that a long-acting central mechanism regulates recovery from apnea induced by SLN stimulation.     

Mechanisms of respiratory response to isoproterenol in glomectomized cats

Effects of intravenous isoproterenol (2-3 micrograms) on arterial pressure, end-tidal CO2 partial pressure (PCO2), medullary extracellular fluid (ECF) pH, and phrenic activity were studied in 13 anesthetized paralyzed cats whose vagi and carotid sinus nerves were cut. The cats were servo-ventilated to keep PCO2 relatively constant. Injections of Ringer solution were without effect. Isoproterenol caused arterial pressure to fall, a transient small (1 Torr) increase of PCO2, increased venous CO2 return to the lungs, a medullary ECF acidosis, and a stimulation of respiration that continued to be elevated after arterial pressure, PCO2, and medullary ECF pH had returned to control. We show that the ECF acidosis is minimally due to the hypotension and to the small transient rise of PCO2. We also show that the respiratory response cannot be explained solely by the ECF acidosis. We conclude that, in addition to its known stimulation of peripheral chemoreceptors, isoproterenol causes medullary ECF to become acidic probably due to metabolic effects on neural tissue and has a separate direct stimulating effect on neurons in the brain.     

Rostral ventrolateral medulla muscarinic receptor involvement in central ventilatory chemosensitivity

The muscarinic receptor antagonist atropine (105 mM) dramatically decreased the response to increased CO2 when applied by cotton pledgets to the rostral ventrolateral medulla ventilatory chemosensitive area in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats with integrated phrenic nerve activity used as respiratory center output. Lower dose atropine (4.4 mM) and the M1-muscarinic receptor subtype antagonist pirenzepine (10 mM) also significantly decreased the mean CO2 response slope 48.3 +/- 6.2 and 40.7 +/- 6.0% (SE), respectively, and significantly decreased the maximum response value 26.3 +/- 8.1 and 19.2 +/- 3.2%, respectively, without significant effects on blood pressure or on the phrenic response to carotid sinus nerve stimulation. The M2-muscarinic receptor subtype antagonist AF-DX 116 (10 mM) had no significant effect on phrenic output or blood pressure. Application of carbachol (10 mM) at the rostral area augmented eucapnic phrenic output and the maximum value of the CO2 response but decreased the initial slope, effects blocked by atropine. Carbachol also decreased the response to carotid sinus nerve stimulation, suggesting that the system was saturated by carbachol stimulation. Muscarinic cholinergic receptors accessible to surface application at the rostral ventrolateral medulla antagonized by pirenzepine but not AF-DX 116 appear to be involved in the central chemoreceptor process.     

Kainic acid on the rostral ventrolateral medulla inhibits phrenic output and CO2 sensitivity

We used the neurotoxin, kainic acid, which is known to stimulate neuronal cell bodies as opposed to axons of passage by binding to specific amino acid receptors to determine whether cells with such receptors have access to the ventrolateral medullary surface and are involved in central ventilatory chemosensitivity. Pledgets with 4.7 mM kainic acid were placed bilaterally on the rostral, intermediate, or caudal ventilatory chemosensitive areas for 1-2 min in chloralose-urethan-anesthetized, paralyzed, vagotomized, glomectomized, and servo-ventilated cats. Application of kainic acid on the caudal or intermediate areas produced no consistent significant effects on eucapnic phrenic output or on the slope or maximum value of the phrenic nerve response to increased end-tidal PCO2. Rostral area kainic acid produced immediate augmentation and then diminution of blood pressure and phrenic output. Apnea developed in six of nine cats by 40 min. In all five cats in which it could be tested, the slope of the CO2 response was clearly decreased. Of [3H]kainic acid applied to the rostral area, 88.4% was shown to be within 2 mm of the ventral surface. Comparison of surface application sites of this and other studies suggests that an area overlapping the border of the original rostral and intermediate areas allows access to neurons involved in the chemoreception process, which may also provide tonic facilitatory input to cardiorespiratory systems.     

Retrofacial lesions: effects on CO2-sensitive phrenic and sympathetic nerve activity.

We made unilateral chemical (10- or 50-nl microinjections; 4.7 mM kainic acid) or electrolytic (5-15 mA; 15 s) lesions in a region of the rostral ventrolateral medulla (VLM) caudal to the retrotrapezoid nucleus in 10 decerebrate, paralyzed, vagotomized, and servo-ventilated cats. The lesions were 3.0-4.2 mm lateral to the midline, within 2 mm caudal to the facial nucleus, and within 2.5 mm of the VLM surface. Four control injections (mock cerebrospinal fluid and fluorescent beads alone) produced small and inconsistent effects over 3-5 h. The predominant effect of the lesions was a significant decrease in baseline integrated phrenic nerve amplitude (PNA) (apnea in 2 cases), total respiratory cycle duration, and the response to increased CO2 (slope < 15% of control in 3 cases). The respiratory-related peak amplitude of the integrated sympathetic signal, blood pressure, and the sympathetic nerve activity response to CO2 were also decreased after the majority of lesions. Not all lesions produced all effects, and some lesions resulted in increased PNA and respiratory cycle duration. The lesioned region appears functionally to represent a caudal extension of the retrotrapezoid nucleus containing neurons necessary for normal baseline PNA and CO2 sensitivity. In addition, it contains neurons involved in the determination of resting respiratory frequency and normal sympathetic activity and blood pressure. The pattern of mixed responses among animals suggests that a heterogeneity of function is present within a relatively small VLM region.     

Awake baboon's ventilatory response to venous and inhaled CO2 loading.

Steady-state ventilatory responses to CO2 in trained awake baboons were studied to determine the response to a venous CO2 load. CO2 was loaded either directly into the venous blood through an arteriovenous shunt or by addition to the inhaled air. The two modes of loading were adjusted to produce the same increase in minute volume. Minute volume, tidal volume respiratory frequency, end-tidal PCO2, PaCO2, and pHa were measured. PaCO2 and PETCO2 increased the same amount during the two modes of CO2 loading; thus, the response to changes in arterial PCO2, deltaVE/deltaPaCO2, was the same. I conclude that the ventilatory response to venous CO2 loading occurs only through the change in mean arterial PCO2 and thus it is unlikely that there are any important venous CO2 receptors.     

Immediate effects of cigarette smoking on cardiorespiratory responses to exercise

To determine the acute action of cigarette smoking on cardiorespiratory function under stress, the immediate effects of cigarette smoking on the ventilatory, gas exchange, and cardiovascular responses to exercise were studied in nine healthy male subjects. Each subject performed an incremental exercise test to exhaustion on two separate days, one without smoking (control) and one after smoking 3 cigarettes/h for 5 h. The order of the two tests was randomized. Arterial blood gases and pH were measured during rest and all levels of exercise; CO blood levels confirmed the absorption of cigarette smoke. In addition, minute ventilation (VE), end-tidal PCO2 and PO2, O2 uptake (VO2), CO2 production, directly measured blood pressure, electrocardiogram, and heart rate (HR) were recorded every 30 s. The dead space-to-tidal volume ratio (VD/VT), maximal aerobic capacity (VO2max), and anaerobic threshold (AT) were determined from the gas exchange data. Cigarette smoking resulted in a significantly lower VO2max, AT, and VO2/HR (O2 pulse) and a significantly higher HR, pulse-pressure product, and pulse pressure (P less than 0.05) compared with the control. Additionally, a trend toward a higher VD/VT and arterial-end-tidal PCO2 difference was found during exercise after smoking. We conclude that cigarette smoking causes immediate detrimental effects on cardiovascular function during exercise, including tachycardia, increased pulse-pressure product, and impaired O2 delivery. The acute effects on respiratory function were less striking and primarily limited to abnormalities reflecting ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)     

End-tidal CO2 response to low levels of inspired CO2 in awake beagle dogs

The steady-state end-tidal CO2 tension (PCO2) was examined during control and 1% CO2 inhalation periods in awake beagle dogs with an intact airway breathing through a low dead-space respiratory mask. A total of eight experiments were performed in four dogs, comprising 31 control observations and 23 CO2 inhalation observations. The 1% inhaled CO2 produced a significant increase in the steady-state end-tidal PCO2 comparable to the expected 1 Torr predicted from conventional CO2 control of ventilation. We conclude that 1% inhaled CO2 results in a hypercapnia. Any protocol that is to resolve the question of whether mechanisms are acting during low levels of inhaled CO2 such that ventilation increases without any change in arterial PCO2 must have sufficient resolving power to discriminate changes in gas tension in magnitude predicted from conventional (i.e., arterial PCO2) control of ventilation.     

Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs.

The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2-3, 14-16, and 21-22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5-7 min each to a maximum 7-8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth.     

Respiratory responses in reversible diaphragm paralysis

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.     

Effects of changes in CO2 partial pressure on the sensation of respiratory drive

The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55-60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded.     

Diethyl pyrocarbonate inhibits rostral ventrolateral medullary H+ sensitivity

Diethyl pyrocarbonate (DEPC), an acylating agent that reacts with imidazole-histidine in vitro, inhibits CO2 sensitivity when applied by pledget to the rostral chemosensitive area on the ventrolateral medullary (VLM) surface in glomectomized, chloralose-urethan-anesthetized cats. In this study similar application of DEPC inhibits the phrenic nerve response to CO2 expressed as a function of VLM [H+] measured by surface pH electrode. Attempts to evaluate direct chemoreceptor stimulation by HCL-soaked surface pledgets proved difficult, but rostral DEPC did inhibit the response to intravenous infusion of HCl. As previously reported, the CO2 and intravenous H+ responses are not a unique function of the VLM [H+]. DEPC had similar inhibitory effects on both the CO2 and the intravenous H+ responses, suggesting that the difference between them may reflect more the orientation or accessibility of the central chemoreceptor than a different mechanism for sensing CO2 vs. H+. DEPC did not alter the phrenic nerve response to hypoxia, indicating that DEPC effects on central chemoreception are not the result of a generalized inhibitory process. The results support the hypothesis that imidazolehistidine is involved at the rostral area with chemoreception of both CO2 and H+.     

Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity

Application by pledget of the M1-antimuscarinic receptor agent pirenzepine (40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats inhibited the slope of the integrated phrenic response to CO2 by 32.5% (P less than 0.03) and the maximum value by 21.1% (P less than 0.01). Similar application of the imidazole-histidine blocking agent diethyl pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and the maximum value by 29.3% (P less than 0.05). Both responses confirm previous results. DEPC treatment decreased the effectiveness of subsequent pirenzepine application such that although slope and maximum were further decreased, the values were not significantly different from those after DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory effect. The results raise the possibility that the inhibitory effects of DEPC on CO2 chemosensitivity are via muscarinic receptors and that muscarinic receptor involvement in CO2 chemosensitivity requires the presence of imidazole-histidine. Analysis by scintillation counting of successive 100-micron sections of medulla after rostral area application of [3H]pirenzepine indicated that the pirenzepine and DEPC effects are most probably within 2.0 mm of the ventral surface as measured from the midline, well away from the dorsal and ventral respiratory group neurons.     

Transient ventilatory response to CO2 as a function of sleep state in full-term infants

The influence of sleep state on the transient (i.e., initial 60 s) and steady-state ventilatory responses to 2% CO2 inhalation was studied in 19 healthy full-term infants. A nasal mask pneumotachometer was used to measure ventilation and end-tidal CO2 partial pressure (PCO2) and enabled abrupt changes in the inspired gas concentration to be made. The magnitude of the change in minute ventilation for both the transient and steady-state responses to CO2 was not statistically different between active (AS) and quiet (QS) sleep. Nonetheless the greater variability in minute ventilation during AS compared with QS continued throughout the period of CO2 inhalation and was associated with a more variable change in ventilation in the individual infants during AS. There was a greater increase in end-tidal PCO2 over the first 60 s during AS (3.3 +/- 0.3 vs. 2.6 +/- 0.2 Torr, in AS and QS, respectively, P less than 0.03). This may indicate a smaller initial increase in alveolar ventilation, relative to CO2 delivery to the lungs, in response to CO2 inhalation during AS. Asynchronous chest wall movements were more common during AS than QS (P less than 0.005) and did not change with CO2. The inconsistent transient ventilatory response to CO2 during AS compared with QS may be important in the behavior of infants to spontaneous episodes of hypercapnia occurring during AS.     

Substance P in the ventrolateral medulla oblongata regulates ventilatory responses.

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.     

Effect of withdrawal of respiratory CO2 oscillations on respiratory control at rest

We examined the effect of sudden withdrawal of respiratory oscillations of arterial PCO2 (CO2 oscillations) at resting metabolic rate on the control of respiration in 11 anesthetized paralyzed vagotomized dogs in normoxic normocapnia. A double-lumen endotracheal tube was inserted so that the left and right lungs were ventilated independently. By alternately ventilating each lung, we could completely abolish CO2 oscillations without affecting the mean blood gas levels (withdrawal of CO2 oscillations). The CO2 oscillation was calculated from arterial pH oscillation measured by a rapidly responding intra-arterial pH electrode. Respiratory center output was monitored by use of a moving time average of the phrenic neurogram. A 3-min period of withdrawal of CO2 oscillations was bracketed by two control periods (simultaneous ventilation of lungs for 3 min) to avoid the confounding effect of the baseline drift in the respiratory center output. The amplitude of the CO2 oscillations in the control was 2.33 +/- 0.89 (SD) Torr. When the difference in the mean level of arterial PCO2 between the control and withdrawal of CO2 oscillations was minimized (-0.09 +/- 0.54 Torr; P greater than 0.25), we found negligible change in the minute phrenic activity during withdrawal of CO2 oscillations (-0.02 +/- 6.11% of the control, P greater than 0.98, n = 49; 99% confidence interval -2.36 to 2.32%). Thus we conclude that the maintenance of normal respiration at rest is not critically dependent on a phasic afferent input to the respiratory center arising from respiratory CO2 oscillations.     

Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study.

The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.