Response time and sensitivity of the ventilatory response to CO2 in unanesthetized intact dogs: central vs. peripheral chemoreceptors

2006 ◽  
Vol 100 (1) ◽  
pp. 13-19 ◽  
Author(s):  
C. A. Smith ◽  
J. R. Rodman ◽  
B. J. A. Chenuel ◽  
K. S. Henderson ◽  
J. A. Dempsey
Keyword(s):  
Steady State ◽  
Carotid Body ◽  
Ventilatory Response ◽  
Periodic Breathing ◽  
Ventilatory Responses ◽  
Central Chemoreceptors ◽  
Carotid Bodies ◽  
Carotid Body Chemoreceptors ◽  
Relative Gains ◽  
Ventilatory Response To Co2

We assessed the speed of the ventilatory response to square-wave changes in alveolar Pco2 and the relative gains of the steady-state ventilatory response to CO2 of the central chemoreceptors vs. the carotid body chemoreceptors in intact, unanesthetized dogs. We used extracorporeal perfusion of the reversibly isolated carotid sinus to maintain normal tonic activity of the carotid body chemoreceptor while preventing it from sensing systemic changes in CO2, thereby allowing us to determine the response of the central chemoreceptors alone. We found the following. 1) The ventilatory response of the central chemoreceptors alone is 11.2 (SD = 3.6) s slower than when carotid bodies are allowed to sense CO2 changes. 2) On average, the central chemoreceptors contribute ∼63% of the gain to steady-state increases in CO2. There was wide dog-to-dog variability in the relative contributions of central vs. carotid body chemoreceptors; the central exceeded the carotid body gain in four of six dogs, but in two dogs carotid body gain exceeded central CO2 gain. If humans respond similarly to dogs, we propose that the slower response of the central chemoreceptors vs. the carotid chemoreceptors prevents the central chemoreceptors from contributing significantly to ventilatory responses to rapid, transient changes in arterial Pco2 such as those after periods of hypoventilation or hyperventilation (“ventilatory undershoots or overshoots”) observed during sleep-disordered breathing. However, the greater average responsiveness of the central chemoreceptors to brain hypercapnia in the steady-state suggests that these receptors may contribute significantly to ventilatory overshoots once unstable/periodic breathing is fully established.

The essential role of carotid body chemoreceptors in sleep apnea

2003 ◽  
Vol 81 (8) ◽  
pp. 774-779 ◽  
Author(s):  
Curtis A Smith ◽  
Hideaki Nakayama ◽  
Jerome A Dempsey
Keyword(s):  
Sleep Apnea ◽  
Carotid Body ◽  
Respiratory Acidosis ◽  
Periodic Breathing ◽  
Peripheral Chemoreceptors ◽  
Carotid Chemoreceptors ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
The Difference ◽  
Carotid Body Chemoreceptors

Sleep apnea is attributable, in part, to an unstable ventilatory control system and specifically to a narrowed "CO2 reserve" (i.e., the difference in PaCO2 between eupnea and the apneic threshold). Findings from sleeping animal preparations with denervated carotid chemoreceptors or vascularly isolated, perfused carotid chemoreceptors demonstrate the critical importance of peripheral chemoreceptors to the ventilatory responses to dynamic changes in PaCO2. Specifically, (i) carotid body denervation prevented the apnea and periodic breathing that normally follow transient ventilatory overshoots; (ii) the CO2 reserve for peripheral chemoreceptors was about one half that for brain chemoreceptors; and (iii) hypocapnia isolated to the carotid chemoreceptors caused hypoventilation that persisted over time despite a concomitant, progressive brain respiratory acidosis. Observations in both humans and animals are cited to demonstrate the marked plasticity of the CO2 reserve and, therefore, the propensity for apneas and periodic breathing, in response to changing background ventilatory stimuli.Key words: sleep apnea, carotid bodies, hypocapnia, apneic threshold, periodic breathing.

Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats

1989 ◽  
Vol 67 (1) ◽  
pp. 186-192 ◽  
Author(s):  
R. A. Wach ◽  
D. Bee ◽  
G. R. Barer
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Response Curves ◽  
Enhancing Effect ◽  
Stimulus Response ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Ventilatory Effects ◽  
Ventilatory Response To Hypoxia

We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2–3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21–12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.

Effects of altered CSF [H+] on ventilatory responses to exercise in the awake goat

1988 ◽  
Vol 65 (2) ◽  
pp. 921-927 ◽  
Author(s):  
C. A. Smith ◽  
L. C. Jameson ◽  
J. A. Dempsey
Keyword(s):  
Steady State ◽  
Carotid Body ◽  
Ventilatory Response ◽  
Fold Increase ◽  
Co2 Production ◽  
Acid Base ◽  
Ventilatory Responses ◽  
Exercise Hyperpnea ◽  
Acid Base Status ◽  
Response To Exercise

We investigated the effects of selective large changes in the acid-base environment of medullary chemoreceptors on the control of exercise hyperpnea in unanesthetized goats. Four intact and two carotid body-denervated goats underwent cisternal perfusion with mock cerebrospinal fluid (CSF) of markedly varying [HCO-3] (CSF [H+] = 21-95 neq/l; pH 7.68-7.02) until a new steady state of alveolar hypo- or hyperventilation was reached [arterial PCO2 (PaCO2) = 31-54 Torr]. Perfusion continued as the goats completed two levels of steady-state treadmill walking [2 to 4-fold increase in CO2 production (VCO2)]. With normal acid-base status in CSF, goats usually hyperventilated slightly from rest through exercise (-3 Torr PaCO2, rest to VCO2 = 1.1 l/min). Changing CSF perfusate [H+] changed the level of resting PaCO2 (+6 and -4 Torr), but with few exceptions, the regulation of PaCO2 during exercise (delta PaCO2/delta VCO2) remained similar regardless of the new ventilatory steady state imposed by changing CSF [H+]. Thus the gain (slope) of the ventilatory response to exercise (ratio of change in alveolar ventilation to change in VCO2) must have increased approximately 15% with decreased resting PaCO2 (acidic CSF) and decreased approximately 9% with increased resting PaCO2 (alkaline CSF). A similar effect of CSF [H+] on resting PaCO2 and on delta PaCO2/VCO2 during exercise also occurred in two carotid body-denervated goats. Our results show that alteration of the gain of the ventilatory response to exercise occurs on acute alterations in resting PaCO2 set point (via changing CSF [H+]) and that the primary stimuli to exercise hyperpnea can operate independently of central or peripheral chemoreception.

Effect of carotid body resection on ventilatory and acid-base control during exercise

1975 ◽  
Vol 39 (3) ◽  
pp. 354-358 ◽  
Author(s):  
K. Wasserman ◽  
B. J. Whipp ◽  
S. N. Koyal ◽  
M. G. Cleary
Keyword(s):  
Steady State ◽  
Metabolic Acidosis ◽  
Carotid Body ◽  
Constant Load ◽  
Incremental Exercise ◽  
Acid Base ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Significant Difference ◽  
Exercise Hyperpnea

To investigate the role of the carotid bodies in exercise hyperpnea and acid-base control, normal and carotid body-resected subjects (CBR) were studied during constant-load and incremental exercise. There was no significant difference in the first-breath ventilatory responses to exercise between the groups; some subjects in each reproducibly exhibited abrupt responses. The subsequent change in Ve toward steady state was slower in the CBR group. The steady-state ventilatory responses were the same in both groups at work rates below the anaerobic threshold (AT). However, above the AT, the hyperpnea was less marked in the CBR group. Ve and acid-base measurements revealed that the CBR group failed to hyperventilate in response to the metabolic acidosis of either constant-load or incremental exercise. We conclude that the carotid bodies 1) are not responsible for the initial exercise hyperpnea, 2) do affect the time course of Ve to its steady state, and 3) are responsible for the respiratory compensation for the metabolic acidosis of exercise.

Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs

2005 ◽  
Vol 98 (5) ◽  
pp. 1732-1739 ◽  
Author(s):  
Bruno J. Chenuel ◽  
Curtis A. Smith ◽  
Kathleen S. Henderson ◽  
Jerome A. Dempsey
Keyword(s):  
Steady State ◽  
Carotid Body ◽  
Pressure Support Ventilation ◽  
Pressure Support ◽  
Ventilatory Response ◽  
Rapid Eye Movement Sleep ◽  
The Difference ◽  
End Tidal ◽  
Carotid Body Chemoreceptors

We determined the effects of specific carotid body chemoreceptor inhibition on the propensity for apnea during sleep. We reduced the responsiveness of the carotid body chemoreceptors using intravenous dopamine infusions during non-rapid eye movement sleep in six dogs. Then we quantified the difference in end-tidal Pco2 (PetCO2) between eupnea and the apneic threshold, the “CO2 reserve,” by gradually reducing PetCO2 transiently with pressure support ventilation at progressively increased tidal volume until apnea occurred. Dopamine infusions decreased steady-state eupneic ventilation by 15 ± 6%, causing a mean CO2 retention of 3.9 ± 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold PetCO2 rose 5.1 ± 1.9 Torr; thus the CO2 reserve was narrowed from −3.9 ± 0.62 Torr in control to −2.7 ± 0.78 Torr with dopamine. This decrease in the CO2 reserve with dopamine resulted solely from the 20.5 ± 11.3% increase in plant gain; the slope of the ventilatory response to CO2 below eupnea was unchanged from normal. We conclude that specific carotid chemoreceptor inhibition with dopamine increases the propensity for apnea during sleep by narrowing the CO2 reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO2 below eupnea was unchanged from normal control. These findings have implications for the role of chemoreceptor inhibition/stimulation in the genesis of apnea and breathing periodicity during sleep.

Ventilatory effects of specific carotid body hypocapnia and hypoxia in awake dogs

1997 ◽  
Vol 82 (3) ◽  
pp. 791-798 ◽  
Author(s):  
Curtis A. Smith ◽  
Craig A. Harms ◽  
Kathleen S. Henderson ◽  
Jerome A. Dempsey
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Inhibitory Effect ◽  
Brain Circulation ◽  
Secondary Purpose ◽  
Central Chemoreceptors ◽  
Inhibitory Feedback ◽  
Ventilatory Effect ◽  
Ventilatory Effects ◽  
Relative Gains

Smith, Curtis A., Craig A. Harms, Kathleen S. Henderson, and Jerome A. Dempsey. Ventilatory effects of specific carotid body hypocapnia and hypoxia in awake dogs. J. Appl. Physiol. 82(3): 791–798, 1997.—Specific carotid body (CB) hypocapnia in the −10-Torr (less than eupneic) range reduced ventilation in the awake and sleeping dog to the same degree as did CB hyperoxia [CB [Formula: see text]([Formula: see text]); >500 Torr; C. A. Smith, K. W. Saupe, K. S. Henderson, and J. A. Dempsey. J. Appl. Physiol. 79: 689–699, 1995], suggesting a powerful inhibitory effect of hypocapnia at the carotid chemosensor over a range of[Formula: see text] encountered commonly in physiological hyperpneas. The primary purpose of this study was to assess the ventilatory effect of CB hypocapnia on the ventilatory response to concomitant CB hypoxia. The secondary purpose was to assess the relative gains of the CB and central chemoreceptors to hypocapnia. In eight awake female dogs the vascularly isolated CB was perfused with hypoxic blood (mild,[Formula: see text]≅ 50 Torr or severe,[Formula: see text]≅ 36 Torr) in a background of normocapnia or hypocapnia (10 Torr less than eupneic arterial [Formula: see text]) in the perfusate. The systemic (and brain) circulation was normoxic throughout, and arterial Pco 2 was not controlled (poikilocapnia). With CB hypocapnia, the peak ventilation (range 19–27 s) in response to hypoxic CB perfusion increased 48% (mild) and 77% (severe) due to increased tidal volume. When CB hypocapnia was present, these increases in ventilation were reduced to 21 and 27%, respectively. With systemic hypocapnia, with the isolated CB maintained normocapnic and hypoxic for >70 s, the steady-state poikilocapnic ventilatory response (i.e., to systemic hypocapnia alone) decreased 15% (mild CB hypoxia) and 27% (severe CB hypoxia) from the peak response, respectively. We conclude that carotid body hypocapnia can be a major source of inhibitory feedback to respiratory motor output during the hyperventilatory response to hypoxic carotid body stimulation.

scholarly journals Contribution of the carotid body chemoreceptors to eupneic ventilation in the intact, unanesthetized dog

2009 ◽  
Vol 106 (5) ◽  
pp. 1564-1573 ◽  
Author(s):  
Grégory M. Blain ◽  
Curtis A. Smith ◽  
Kathleen S. Henderson ◽  
Jerome A. Dempsey
Keyword(s):  
Steady State ◽  
Carotid Body ◽  
Sensory Input ◽  
Carotid Sinus ◽  
Respiratory Acidosis ◽  
Tonic Activity ◽  
Inspiratory Flow Rate ◽  
Compensatory Response ◽  
Per Se ◽  
Carotid Body Chemoreceptors

We used extracorporeal perfusion of the reversibly isolated carotid sinus region to determine the effects of specific carotid body (CB) chemoreceptor inhibition on eupneic ventilation (V̇i) in the resting, awake, intact dog. Four female spayed dogs were studied during wakefulness when CB was perfused with 1) normoxic, normocapnic blood; and 2) hyperoxic (>500 mmHg), hypocapnic (∼20 mmHg) blood to maximally inhibit the CB tonic activity. We found that CB perfusion per se (normoxic-normocapnic) had no effect on V̇i. CB inhibition caused marked reductions in V̇i (−60%, range 49–80%) and inspiratory flow rate (−58%, range 44–87%) 24–41 s following the onset of CB perfusion. Thereafter, a partial compensatory response was observed, and a steady state in V̇i was reached after 50–76 s following the onset of CB perfusion. This steady-state tidal volume-mediated hypoventilation (∼31%) coincided with a significant reduction in mean diaphragm electromyogram (−24%) and increase in mean arterial pressure (+12 mmHg), which persisted for 7–25 min until CB perfusion was stopped, despite a substantial increase in CO2 retention (+9 Torr, arterial Pco2) and systemic respiratory acidosis. We interpret these data to mean that CB chemoreceptors contribute more than one-half to the total eupneic drive to breathe in the normoxic, intact, awake animal. We speculate that this CB contribution consists of both the normal tonic sensory input from the CB chemoreceptors to medullary respiratory controllers, as well as a strong modulatory effect on central chemoreceptor responsiveness to CO2.

An assessment of nasal functions in control of breathing

1988 ◽  
Vol 65 (4) ◽  
pp. 1520-1524 ◽  
Author(s):  
Y. Tanaka ◽  
T. Morikawa ◽  
Y. Honda
Keyword(s):  
Steady State ◽  
Dead Space ◽  
Airway Resistance ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
Control Of Breathing ◽  
Mouth Breathing ◽  
Occlusion Pressure ◽  
Ventilatory Responses ◽  
End Tidal

Breathing pattern and steady-state CO2 ventilatory response during mouth breathing were compared with those during nose breathing in nine healthy adults. In addition, the effect of warming and humidification of the inspired air on the ventilatory response was observed during breathing through a mouthpiece. We found the following. 1) Dead space and airway resistance were significantly greater during nose than during mouth breathing. 2) The slope of CO2 ventilatory responses did not differ appreciably during the two types of breathing, but CO2 occlusion pressure response was significantly enhanced during nose breathing. 3) Inhalation of warm and humid air through a mouthpiece significantly depressed CO2 ventilation and occlusion pressure responses. These results fit our observation that end-tidal PCO2 was significantly higher during nose than during mouth breathing. It is suggested that a loss of nasal functions, such as during nasal obstruction, may result in lowering of CO2, fostering apneic spells during sleep.

Carotid body chemoreceptor reflexes and their interactions in the seal

1977 ◽  
Vol 232 (5) ◽  
pp. H517-H525 ◽  
Author(s):  
R. Elsner ◽  
J. E. Angell-James ◽  
M. de Burgh Daly
Keyword(s):  
Carotid Body ◽  
Superior Laryngeal Nerve ◽  
Harbor Seal ◽  
Minute Volume ◽  
Respiratory Response ◽  
Carotid Bodies ◽  
The Central Nervous System ◽  
Carotid Body Chemoreceptors ◽  
Spontaneously Breathing ◽  
Stimulation Of

In the anesthetized spontaneously breathing harbor seal Phoca vitulina stimulation of the carotid body chemoreceptors by intracarotid injections of sodium cyanide or by hypoxic hypercapnic blood causes an increase in tidal volume, respiratory frequency, and respiratory minute volume. The heart rate invariably decreased. Experimental dives caused apnea and bradycardia. When the carotid bodies are stimulated within 10 s of the commencement of a dive, the chemoreceptor-respiratory response is abolished, but the chemoreceptor-cardioinhibitory response is considerably enhanced. Electrical stimulation of the central cut end of a superior laryngeal nerve also causes apnea and bradycardia; stimulation of the carotid body now fails to produce a respiratory response but the cardioinhibitory effect is enhanced. These results indicate that the carotid bodies cause reflexly hyperventilation and bradycardia, and that these responses are considerably modified by other inputs to the central nervous system.

The Ventilatory Effects of Doxapram in Normal Man

1983 ◽  
Vol 65 (1) ◽  
pp. 65-69 ◽  
Author(s):  
P. M. A. Calverley ◽  
R. H. Robson ◽  
P. K. Wraith ◽  
L. F. Prescott ◽  
D. C. Flenley
Keyword(s):  
Oxygen Uptake ◽  
Ventilatory Response ◽  
Co2 Production ◽  
Central Action ◽  
Ventilatory Responses ◽  
Ventilatory Effects ◽  
Normal Man ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Ventilatory Response To Co2

1. To determine the mode of action of doxapram in man we have measured ventilation, oxygen uptake, CO2 production, hypoxic and hypercapnic ventilatory responses in six healthy men before and during intravenous infusion to maintain a constant plasma level. 2. Doxapram changed neither resting oxygen uptake nor CO2 production but produced a substantial increase in resting ventilation at both levels of end-tidal CO2 studied. 3. Doxapram increased the ventilatory response to isocapnic hypoxia from − 0.8 ± 0.4 litre min−1 (%Sao2)−1 to −1.63 ± 0.9 litres min−1 (%Sao2)−1. This was similar to the increase in hypoxic sensitivity which resulted from raising the end-tidal CO2 by 0.5 kPa without adding doxapram. 4. The slope of the ventilatory response to rebreathing CO2 rose from 11.6 ± 5.3 litres min−1 kPa−1 to 20,4 ± 9.8 litres min−1 kPa−1 during doxapram infusion. 5. The marked increase in the ventilatory response to CO2 implies that doxapram has a central action, but the potentiation of the hypoxic drive also suggests that the drug acts on peripheral chemoreceptors, or upon their central connections, at therapeutic concentrations in normal unanaesthetized subjects.

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