Carotid body chemoreceptor and ventilatory responses to sustained hypoxia and hypercapnia in the cat

To understand the role of carotid chemoreceptor activity in the ventilatory responses to sustained hypoxia (30 min) the following measurements were made in cats anesthetized with alpha-chloralose: (1) carotid chemoreceptor and ventilatory responses to isocapnic hypoxia and to hypercapnia during hyperoxia; (2) carotid chemoreceptor responses to isocapnic hypoxia after dopamine receptor blockade; and (3) ventilatory responses to hypoxia after bilateral section of carotid sinus nerves (CSN). Transition to hypoxia (PaO2 approximately equal to 52 Torr) from hyperoxia gradually increased carotid chemoreceptor activity by ten fold and ventilation by two fold without any detectable overshoot. Termination of isocapnic hypoxia with hyperoxia (PaO2 greater than 300 Torr) at 30 min promptly restored the carotid chemoreceptor activity to prehypoxic level. Ventilation also decreased promptly, but remained above the control value. Induction of hypercapnia (from 31.8 Torr to 43.9 Torr) during hyperoxia was followed by a prompt increase in the chemoreceptor activity by four fold which subsequently diminished, and by a gradual four fold increase in ventilation. Termination of hypercapnia after 30 min was followed by a prompt return of chemoreceptor activity and by a slow return of ventilation to near control levels. Dopamine receptor blockade increased carotid chemoreceptor responsiveness to acute hypoxia but did not alter the response pattern during sustained hypoxia. After bilateral CSN section, ventilation decreased during maintained hypoxia. Thus, a stimulatory peripheral and inhibitory central effects of hypoxia could produce a biphasic ventilatory response to short-term hypoxia in the anesthetized cat with intact CSN but did not manifest it. The results suggest that the chemosensory input not only promptly stimulates ventilation but also prevents the subsequent depressant effect of hypoxia on the brain-stem respiratory mechanisms and hence presumably a biphasic ventilatory response in the anesthetized cat.     

Hypoxic ventilatory control in the awake cat five years after carotid body resection

Steady state breathing patterns, alveolar gases, and arterial blood gases and pH were measured during air, acute hypoxia, and acute hyperoxia in four awake cats 5 years after combined carotid body resection (CBR) and aortic depressor nerve section. Steady state breathing patterns and alveolar gases were also measured in these animals following 3 days of hypoxia (PIO2 = 110 Torr). The results show that the awake cat without carotid bodies and aortic depressor nerves hypoventilates during normoxia in relation to intact cats. Acute hypoxia resulted in respiratory acidosis, decreased tidal volume (VT), and decreased breath duration (TTOT). Exposure to hypoxia for three days resulted in no hyperventilation (isocapnia) but increased VT and TTOT from their levels during acute hypoxia. Acute hyperoxia resulted in respiratory alkalosis and increased VT. Moderate degrees of acute inspiratory hypoxia (FIO2 less than 0.12) induced a behavioral 'arousal' in these cats; this is in direct contrast to the lack of response seen shortly after CBR. Presumably, the recrudescence of chemosensitivity via unsectioned aortic chemoreceptor afferents played a key role in the arousal responses. However, there is no evidence in the cat for recrudescent chemoreceptor input to the respiratory control system with measurable steady state effect. We conclude that the peripheral chemoreceptors are essential for normal resting ventilatory control and for acclimation to chronic hypoxia.     

Effects of normobaric and hypobaric hypoxia on ventilation and arterial blood gases in ducks

We measured ventilation (V1) and arterial blood gases in awake Pekin ducks exposed to normoxia at sea level, normobaric hypoxia achieved by lowering FIO2 at normal barometric pressure (NORMO), and hypobaric hypoxia achieved with a low pressure chamber and 21% O2 (HYPO). Average normoxic values were: V1 = 0.46 L . (kg.min)-1, PaO2 = 99.7 Torr, PaCO2 = 30.1 Torr. At PIO2 = 90 Torr, NORMO and HYPO measurements were not significantly different (P greater than 0.05). At PO2 = 46 Torr, NORMO V1 was less than HYPO V1 but blood gases were not significantly different: VI = 1.00 vs 1.45 L . (kg.min)-1; PaO2 = 31.3 vs 33.0 Torr; PaCO2 = 11.5 vs 10.6 Torr. Although both tidal volume (VT) and respiratory frequency (fR) were greater in HYPO, similar blood gases with NORMO and HYPO suggest similar parabronchial ventilation. The results suggest increased physiologic dead space, caused by reduced efficacy of aerodynamic valving, with reduced gas density in hypobaria.     

An analysis of respiratory frequency alterations in vagotomized, decerebrate cats.

Changes in inspiratory (TI), expiratory (TE) and total respiratory cycle (TTOT) durations with hypercapnia- of hypoxia-induced tidal volume (VT) elevations were evaluated in midcollicular decerebrate cats. As VT increased, TI, TE, and TTOT decreased for most animals having intact vagi. Following vagotomy, TI, TE, and TTOT increased with hypercapnia for cats which had TI, TE and TTOT values shorter than 1.6, 3.7 and 5.2 sec respectively while breathing 100% O2; values longer than these forecast hypercapnia-induced decreases in each parameter. Similar systematic changes were not evident for hypoxia-induced responses. Varying the midbrain transection level or pentobarbital administration altered TI, TE and TTOT values while breathing 100% O2; however, the predictability of hypercapnia-induced responses, based on data analysis from midcollicular decerebrate cats, was maintained. It is concluded that the vagally-independent brainstem frequency controller is sensitive to hypercapnia and hypoxia. The predictability of hypercapnia-induced TI, TE and TTOT changes in vagotomized animals is considered in the context of previous models for respiratory rhythm generation.     

Aortic and carotid body chemoreception in prolonged hyperoxia in the cat.

Carotid body chemosensory response to hypoxia is attenuated as a result of prolonged normobaric hyperoxia (NH) in the cat. The effect of NH is likely to be due to high cellular PO2 and O2-related free radicals. Accordingly, the effect would be less if O2 delivery to the chemoreceptor tissue could be compromised. The aortic bodies, which appear to have less of a circulatory O2 delivery, as suggested by their vigorous responses to a slight compromise of O2 flow compared with those of the carotid body, could provide a suitable testing material for the hypothesis. We tested the hypothesis by studying both aortic and carotid body chemoreceptors in the same cats (n = 6) which were exposed to nearly 100% O2 for about 60 h. These chemoreceptor organs were also studied in 6 control cats which were maintained in room air at sea-level. The cats were anesthetized and their carotid and aortic chemosensory fibers were identified by the usual procedure, and their responses to hypoxia and hypercapnia and to bolus injections (i.v.) of cyanide and nicotine were measured. In the NH cats, the carotid but not aortic chemosensory responses to hypoxia and cyanide were attenuated and to hypercapnia (both onset and steady state) augmented. The aortic chemoreceptors were stimulated by hypoxia, hypercapnia, cyanide and nicotine both in the NH and the control cats similarly. The results support the hypothesis that it is presumably a higher tissue blood flow and hence a higher concentration of O2-related free radicals which ultimately led to the specific attenuation of O2 chemoreception in the carotid body.     

Respiratory patterns in anesthetised rats before and after anemic decerebration.

Experiments were undertaken to test the comparability of changes in respiratory frequency and tidal volume during hypoxia and hypercapnia in rats with and without intact peripheral chemoreceptors and with intact vagi. Neural organisation of respiratory control was perturbed by anemic decerebration, achieved by ligation of the common carotid and basilar arteries. Ischemia of the brain was produced as far candal as the rostral pontine nuclei involved in respiratory control but left the medulla well perfused. The dominant respiratory effect in animals breathing air or oxygen was polypnea with hypocapnia (mean PaCO2 when breathing air 24.7 mmHg, when breathing oxygen 29.6 mmHg). After decerebration the increase of ventilation produced by breathing 10% O2 in N2 was reduced compared with responses in the intact state but levels of ventilation (V1) in hypoxia were similar to those before decerebration. After decerebration, the increase of ventilation produced by breathing 5% CO2 was greatly reduced and the level of V1 in animals breathing CO2 was significantly less than in the intact state. Intermediate changes were seen in animals breathing 2-3% CO2 which converted the hypocapnia (PaCO2 30.9 mmHg) to eucapnia (PaCO2 46.4 mmHg). In the intact state, hypoxia dominantly caused increased frequency (f) and hypercapnia caused increased tidal volume (VT); after decerebration, hypoxia produced reduction of VT while hypercapnia produced reduction of f. Bilateral carotid sinus nerve section in decerebrate animals eliminated the ventilatory response to hypoxia but left the responses to hypercapnia unaltered. The results point to differences in the mechanisms by which hypoxia and hypercapnia influence respiration in both intact and decerebrate animals with carotid sinus and vagus nerves functional. The differences can now be interpreted in terms of specific neural features of respiratory control.     

Hyperoxic ventilatory responses of high altitude acclimatized cats

We have examined the effect of steady-state hyperoxia on the ventilation of sea level (SL) cats and cats acclimatized to simulated high altitude (HA) at 5500 m for three weeks. Three groups of cats were studied. In group I, the ventilatory responses to 10%, 21% and 100% O2 were studied at SL, and after acclimatization to HA, the ventilatory responses to 10% and 100% O2 were measured. In group II the ventilatory responses and femoral artery and superior sagittal sinus blood gases were measured in two sets of cats, one at SL and one at HA, during exposure to the gases outlined in group I. In group III, we examined the effect of chronic vagotomy on the ventilatory responses to the gas mixtures outlined in group I. Breathing 100% O2 at SL had no significant effect on ventilation, tidal volume, respiratory frequency, or cerebral blood flow (inferred from the cerebral veno-arterial CO2 difference). Ventilation was constant in the HA acclimatized cats while breathing 10% and 100% O2, but the ventilatory pattern changed dramatically during hyperoxia: respiratory frequency increased and tidal volume fell. Breathing 100% O2 was associated with changes in CBF, and venous PCO2 that might be expected to stimulate ventilation, but the change in ventilatory pattern suggests to us that hyperoxic disinhibition of central respiratory processes (which were modified by HA acclimatization) is the mechanism whereby ventilation is sustained during hyperoxia at HA. After vagotomy at HA, ventilation remained constant while breathing 100% O2, but the changes in respiratory pattern were no longer apparent. Therefore, vagal afferents seems to have a role in determining the pattern, but not necessarily the absolute level, of ventilation during hyperoxia. Cats vagotomized at SL prior to HA exposure did not show any evidence of HA ventilatory acclimatization; thus, the vagi may also play a heretofore unrecognized role in the process of acclimatization.     

Inhibitory and excitatory effects on respiration by phrenic nerve afferent stimulation in cats

Respiratory effects of electrical stimulation of phrenic nerve afferents were studied in anesthetized cats, either spontaneously breathing or paralyzed and ventilated. The type of phrenic afferent fibers activated was controlled by recording the evoked action potentials from dorsal root fibers. In both preparations, stimulation at a strength sufficient to activate small diameter myelinated phrenic nerve afferents induced a biphasic response. The first phase lasted a few respiratory cycles and was inhibitory and consisted of a decrease in tidal volume (VT) or phrenic activity (NA), inspiratory time (TI), respiratory duty cycle (TI/Ttot) and instantaneous ventilation (VE) or minute phrenic activity (NMA). Expiratory time (TE) increased and breathing frequency (f) and mean inspiratory flow (VT/TI) or mean inspiratory neural activity (NA/TI) did not change. This short-term response was suppressed in animals pretreated with bicuculline. The second phase was a long-term excitation in which VT or NA, f, VE or NMA and VT/TI increased whereas both TI and TI/Ttot decreased and TE did not change. Unlike published data, our results suggest that small-diameter myelinated phrenic nerve afferents are involved in these responses. These phrenic fibers, like afferents from other muscles, affect respiratory output and may play a role in the control of breathing.     

A model of the chemoreflex control of breathing in humans: model parameters measurement

We reviewed the ventilatory responses obtained from rebreathing experiments on a population of 22 subjects. Our aim was to derive parameter estimates for an 'average subject' so as to model the respiratory chemoreflex control system. The rebreathing technique used was modified to include a prior hyperventilation, so that rebreathing started at a hypocapnic P(CO2) and ended at a hypercapnic P(CO2). In addition, oxygen was added to the rebreathing bag in a controlled manner to maintain iso-oxia during rebreathing, which allowed determination of the response at several iso-oxic P(O2) levels. The breath-by-breath responses were analysed in terms of tidal volume, breathing frequency and ventilation. As P(CO2) rose, ventilation was first steady at a basal value, then increased as P(CO2) exceeded a breakpoint. We interpreted this first breakpoint as the threshold of the combined central and peripheral chemoreflex responses. Above, ventilation increased linearly with P(CO2), with tidal volume usually contributing more than frequency to the increase. When breathing was driven strongly, such as in hypoxia, a second breakpoint P(CO2) was often observed. Beyond the second breakpoint, ventilation continued to increase linearly with P(CO2) at a different slope, with frequency usually contributing more than tidal volume to the increase. We defined the parameters of the variation of tidal volume, frequency and ventilation with P(O2) and P(CO2) for an average subject based on a three-segment linear fit of the individual responses. These were incorporated into a model of the respiratory chemoreflex control system based on the general scheme of the 'Oxford' model. However, instead of considering ventilatory responses alone, the model also incorporates tidal volume and frequency responses.     

Effect of intermittent mandatory ventilation on respiratory drive and timing

Seven patients receiving chronic ventilatory support were studied to better define the effects of intermittent mandatory ventilation (IMV) on the control and timing of spontaneous breathing between mandatory breaths. Each of these patients could sustain adequate spontaneous ventilation, as reflected by stable end-tidal carbon dioxide concentration (FETCO2), and arterial oxygen saturation (SO2) during periods of unassisted ventilation of sufficient duration to allow study. Inspiratory time (TI), respiratory cycle duration (Ttot), tidal volume (VT), and tracheal occlusion pressure (P0.1) were measured as IMV rate was progressively reduced. Respiratory timing was unaltered by decreasing IMV frequency; however, VT increased progressively. The P0.1 and mean inspiratory flow rate (VT/TI) also increased with each decrease in IMV rate, whereas FETCO2 and arterial SO2 remained constant. Thus, in these stable but ventilator-dependent patients, IMV did not alter respiratory timing or chemical stimuli, but it did alter respiratory drive as measured by VT/TI and P0.1.     

Upper airway function and non-intubated, assisted ventilation

The influence of upper airway patency on ventilation assisted by chest negative pressure ventilation (CNPV) or nasal intermittent positive pressure ventilation (nIPPV) was studied as follows. 1) In seven patients with chronic respiratory failure (PaCO2 more than 50 Torr), the increase in tidal volume (VT) induced by CNPV was larger during mouth breathing than during nose breathing in the awake state. On CNPV transcutaneous PCO2 (PtcCO2) decreased during awake state, but increased during NREM sleep. 2) In four patients with chronic respiratory failure (PaCO2 more than 60 Torr), nIPPV induced the leakage of air from mouth in more than 20 cmH2O of nasal mask pressure during sleep. PtcCO2 increased during sleep, especially during REM sleep in spite of nIPPV. The change in PtcCO2 during REM sleep on nIPPV comparing awake state was 16.1 +/- 1.4 torr and comparing REM sleep in usual sleep was -6.0 +/- 1.4 Torr. 3) Upper airway resistance (UAR) was measured in two patients with tracheostomy. An increase in UAR was associated with a linear decrease in VT during nIPPV, although associated with a curvilinear decrease in VT during CNPV. These results indicate that the efficiency of CNPV and nIPPV depends on the patency of upper airway.     

Role of the carotid bodies in ventilatory acclimation to chronic hypoxia by the awake cat

Steady-state breathing patterns during air and hypoxia (PIO2 = 84 Torr) were measured in awake cats in the following conditions: (1) during 7 months of exposure to air following carotid body resection (CBR; N = 6); (2) during 7 months of hypobaric hypoxia (PIO2 = 84 Torr; N = 5) following CBR; (3) during 5 months of exposure to hypobaric hypoxia (N = 4) while intact and then following CBR. Also, in groups (1) and (2) the aortic nerves were sectioned (ANX) at the end of the acclimation periods. The results show that the awake cat hypoventilates if the carotid bodies have been removed, and hypoxic sensitivity is reduced during long-term exposures to either hypoxia or normoxia. ANX caused a slight increase in respiratory frequency, indicating a minor role for the aortic bodies. CBR after acclimation to hypoxia resulted in decreased tidal volume but no change in respiratory frequency. The slight ventilatory acclimation to hypoxia in CBR cats was solely due to increased respiratory frequency. The phenomenon of 'hypoxic tachypnea' was modulated by acclimation, indicating that the effect of hypoxic acclimation upon respiratory frequency is due to central mechanisms.     

The mechanism of rapid shallow breathing due to histamine and phenyldiguanide in cats and rabbits

In anaesthetized cats and rabbits we analyzed the rapid shallow breathing following exposure to histamine aerosol (mainly an irritant receptor stimulant) and i.v. injection of phenyldiguanide (mainly a J receptor stimulant). Both drugs caused a marked leftward displacement of the tidal volume (VT) vs inspiratory time (TI) relationship (Hering-Breuer threshold curve) without a corresponding increase in inspiratory flow rate so that inspiration was cut off at a lower VT and TI. The leftward displacement of the VT vs TI relationship occurred with a great shortening of the duration of inspiration during occluded breaths (T0I) accompanied by a shortening of the expiratory phase (T0E). These parameters monitored the central respiratory rhythm in absence of the phasic lung volume related vagal loop. It is suggested that the increased central respiratory frequency was due to the augmented firing of fibers from stimulated irritant and J receptors. Stimulation of these endings also caused the TE vs TI relationship to become steeper in cats and to be displaced downwards in rabbits.     

Respiratory response to histamine- and methylcholine-induced bronchospasm in nonsmokers and asymptomatic smokers

The respiratory response to bronchospasms of the same magnitude induced by inhalation of histamine or methylcholine was measured non-invasively, using bellow pneumographs, in nonsmokers and asymptomatic smokers. In each subject, tidal volume (VT), breathing frequency (f) and inspiratory time (TI) were obtained on two different days, in a randomized crossover fashion, with the following sequence: basal conditions, after inhalation of buffered saline as a control and after histamine or methylcholine inhalation. Basal and control conditions did not differ from each other and were the same for both groups. The respiratory responses to both bronchoconstrictors did not differ from each other and were also the same in both groups: VT increased, f and TI remained unchanged. Thus, VT/TI, an index of respiratory drive, also increased. In nonsmokers the increased VT/TI and the associated increase in minute ventilation were both correlated to the decrease in FEV1. These correlations were not found in smokers. Although they have different effects on airway irritant receptors, inhaled histamine and methylcholine induce the same respiratory response in nonsmokers and smokers. Thus, the presumed smoking-related changes in airway mucosa permeability do not seem to influence the direct stimulating effect of histamine on these endings. The absence of correlation between FEV1 and VT/TI changes in smokers suggest that smoking might affect the respiratory drive in acute drug-induced bronchospasm.     

Peripheral and central dopamine receptors in respiratory control

The role of peripheral and central dopaminergic mechanisms in respiratory control was studied in anesthetized cats. In one series, we simultaneously measured carotid chemoreceptor and ventilatory responses to hypoxia and hypercapnia before and after a saturation dose of intravenous domperidone, a peripheral dopamine (D2) receptor antagonist. Both carotid chemoreceptor and ventilatory responses were augmented by domperidone essentially in proportion, suggesting that they reflected the increase of peripheral chemoreceptor activity. Haloperidol which crosses into the brain from blood, given subsequent to domperidone, did not further affect carotid chemoreceptor responses but attenuated ventilatory responses to hypoxia without significantly altering those to hypercapnia. Thus, the additional ventilatory effect of haloperidol is mediated through central dopaminergic mechanisms involving peripheral chemoreflex pathway alone. In another series, the anesthetized cats were paralyzed and artificially ventilated to study carotid chemoreceptor responses to step increases in the end-tidal PCO2 before and after domperidone. Domperidone significantly augmented the responses to CO2. The results support the hypothesis that both peripheral and central dopaminergic mechanisms play a significant modulatory role in chemoreflex respiratory control.     

Mechanics of breathing during strenuous exercise in Thoroughbred horses

The changes induced by exercise on the mechanics of breathing, as well as the simultaneous changes occurring in arterial blood gas tensions and in respiratory gas exchange were investigated in 6 healthy thoroughbred horses, performing a treadmill exercise of increasing intensity. Respiratory airflow and tidal volume (VT) were measured with ultrasonic flowmeters. Pleural pressure changes were measured by an oesophageal balloon catheter. Gas concentration of the expired air was analysed with a mass spectrometer; the oxygen consumption (VO2) and the carbon dioxide output (VCO2) were computed breath-by-breath. Arterial blood gas values were obtained by sampling from the carotid artery. Between rest and fast gallop VT, respiratory frequency, expired minute ventilation (VE), VO2, VCO2, total pulmonary resistance (RL), mechanical work of breathing (Wrm) and PaCO2 increased significantly while PaO2 decreased significantly. The Wrm.VO2(-1) ratio in galloping horses increased exponentially with VE. This, together with the relationship between the changes in PaO2 and in PaCO2 and the increase in the ventilatory mechanics parameters, suggests that the mechanics of breathing may be one of the factors constraining further increase in ventilation in exercising healthy horses.     

The effect of obliterative bronchiolitis on breathing pattern during exercise in recipients of heart-lung transplants

The more rapid and shallow ventilation pattern seen during exercise in patients with obstructive and/or restrictive lung disease has been attributed by some investigators to the effects of vagal afferents from intrapulmonary receptors. Recipients of heart-lung transplants (HLTR) offer a unique opportunity to test this hypothesis since they have denervated lungs and may develop obliterative bronchiolitis after organ rejection. We thus compared the ventilation responses to incremental bicycle ergometry of five HLTR with relatively normal pulmonary function (HLTR-N) and four with bronchiolitis obliterans (HLTR-O). We compared the slopes of the linear portion of the tidal volume versus inspired minute ventilation relationship of both groups. The rate of rise of tidal volume (VT) (slope of VT versus VI) was greater in HLTR-N (0.31 +/- 0.004) than in HLTR-O (0.023 +/- 0.007) (p less than 0.05). This corresponded to a slower increase in respiratory rate (RR) (slope of RR versus Vl/cm) in HLTR-N (0.055 +/- 0.005) than in HLTR-O (0.083 +/- 0.019) (p less than 0.01). Furthermore, values for VT, inspiratory time (TI), and duty cycle (TI/Ttot) measured during exercise at the VT break point were all significantly lower in the HLTR-O than in HLTR-N. We also evaluated the ability of HLTR with lung disease to regulate their ultimate level of ventilation during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory response to positive and negative inspiratory pressure in humans.

To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end-tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands.     

Effects of volume and frequency of mechanical ventilation on respiratory activity in humans

This study evaluated the interaction between respiratory chemical drive and non-chemical factors related to the frequency and level of thoracic displacement during mechanical ventilation in shaping respiratory activity. Ten normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator to a baseline end-tidal PCO2 of approximately 30 Torr. Thereafter, in separate trials, the end-tidal PCO2 was increased by (a) progressively raising the concentration of CO2 in the inspired gas (FICO2) while holding tidal volume (VT) and breathing frequency (f) constant, (b) lowering f while holding VT and FICO2 constant, and (c) lowering VT while maintaining a constant f and FICO2. Initially, as the PCO2 rose above baseline levels with increases in FICO2, there was no change in inspiratory muscle activity, as measured by the peak inspiratory airway pressure, until the PCO2 reached 40 Torr. This PCO2 threshold for a change in respiratory activity was significantly reduced when the tidal volume or frequency of mechanical ventilation was lowered. These results suggest that non-chemical drives related to the frequency and level of thoracic displacement interact with chemical stimuli in shaping respiratory activity.     

Control of metabolic and ventilatory responses to cold in anesthetized cats.

Interactions between the control of thermogenesis and ventilation were studied during normoxia, hyperoxia, and ambient or CO hypoxia in adult anesthetized intact or carotid-denervated cats. Shivering, metabolic and ventilatory responses to cold stress were studied. In addition, the effects of transient pharmacological stimulation (NaCN) or inhibition (Dopamine) of arterial chemoreceptor activity were studied under different levels of oxygenation. In intact animals, cold exposure provoked increases in VO2 and ventilation which were directly proportional to the intensity of shivering. During ambient or CO hypoxia, VO2 was less than in normoxia for all values of shivering intensity, suggesting that a non-shivering thermogenesis component may also be inhibited by hypoxia. The decrease in VO2 was associated with a smaller decrease in ventilation in ambient than in CO hypoxia because of the presence of the chemoreflex drive during ambient hypoxia. Pharmacological changes in chemoreceptor activity induced transient and opposite changes in ventilation and shivering intensity, confirming their role in the control of thermogenesis. After carotid denervation, when the drug effects were inconsistent or absent, changes in levels of oxygenation were still followed by changes in shivering activity and associated changes in VO2 and ventilation. We conclude that control of thermogenesis and ventilation and their interaction may be mediated by chemoreceptors as well as by direct effects upon central, possibly diencephalic structures.