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.

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.

Relative responses of aortic body and carotid body chemoreceptors to carboxyhemoglobinemia

1981 ◽  
Vol 50 (3) ◽  
pp. 580-586 ◽  
Author(s):  
S. Lahiri ◽  
E. Mulligan ◽  
T. Nishino ◽  
A. Mokashi ◽  
R. O. Davies
Keyword(s):  
Carbon Monoxide ◽  
Carotid Body ◽  
Carotid Chemoreceptors ◽  
State Response ◽  
Discharge Rates ◽  
Carotid Bodies ◽  
Tissue Po2 ◽  
Stimulus Source ◽  
Carotid Body Chemoreceptors ◽  
O2 Delivery

The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.

Carotid body excision significantly changes ventilatory control in awake rats

1988 ◽  
Vol 64 (2) ◽  
pp. 666-671 ◽  
Author(s):  
E. B. Olson ◽  
E. H. Vidruk ◽  
J. A. Dempsey
Keyword(s):  
Carotid Body ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Respiratory Acidosis ◽  
Co2 Production ◽  
Sham Operation ◽  
Ventilatory Responses ◽  
Carotid Body Chemoreceptors ◽  
Arterial Po2 ◽  
Intact Rats

We determined the effects of carotid body excision (CBX) on eupneic ventilation and the ventilatory responses to acute hypoxia, hyperoxia, and chronic hypoxia in unanesthetized rats. Arterial PCO2 (PaCO2) and calculated minute alveolar ventilation to minute metabolic CO2 production (VA/VCO2) ratio were used to determine the ventilatory responses. The effects of CBX and sham operation were compared with intact controls (PaCO2 = 40.0 +/- 0.1 Torr, mean +/- 95% confidence limits, and VA/VCO2 = 21.6 +/- 0.1). CBX rats showed 1) chronic hypoventilation with respiratory acidosis, which was maintained for at least 75 days after surgery (PaCO2 = 48.4 +/- 1.1 Torr and VA/VCO2 = 17.9 +/- 0.4), 2) hyperventilation in response to acute hyperoxia vs. hypoventilation in intact rats, 3) an attenuated increase in VA/VCO2 in acute hypoxemia (arterial PO2 approximately equal to 49 Torr), which was 31% of the 8.7 +/- 0.3 increase in VA/VCO2 observed in control rats, 4) no ventilatory acclimatization between 1 and 24 h hypoxia, whereas intact rats had a further 7.5 +/- 1.5 increase in VA/VCO2, 5) a decreased PaCO2 upon acute restoration of normoxia after 24 h hypoxia in contrast to an increased PaCO2 in controls. We conclude that in rats carotid body chemoreceptors are essential to maintain normal eupneic ventilation and to the process of ventilatory acclimatization to chronic hypoxia.

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.

Breathing periodicity in intact and carotid body-denervated ponies during normoxia and chronic hypoxia

1993 ◽  
Vol 74 (3) ◽  
pp. 1073-1082 ◽  
Author(s):  
D. R. Brown ◽  
H. V. Forster ◽  
A. S. Greene ◽  
T. F. Lowry
Keyword(s):  
Carotid Body ◽  
Chronic Hypoxia ◽  
Pulmonary Ventilation ◽  
Periodic Breathing ◽  
Total Power ◽  
Fast Fourier Transformation ◽  
Periodic Oscillations ◽  
Carotid Chemoreceptors ◽  
Induced Changes ◽  
Arterial Po2

Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40–50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063–0.500 cycles/breath were observed in all parameters during both normoxia and hypoxia. During normoxia, CBD accentuated periodicity of VT (P < 0.02) and VI (P < 0.01) but did not change TI or TE periodicity (P > 0.05). These findings suggest that carotid chemoreceptors serve to stabilize breathing (i.e., decrease periodicity) during normoxia, conceivably because of their shorter response time compared with that of central chemoreceptors. During certain periods of hypoxia, periodicity of VT and VI was significantly (P < 0.05) increased in intact ponies. The response to hypoxia in CBD ponies was variable, with VI periodicity significantly (P < 0.05) increasing, decreasing, or unchanging. Because some CBD ponies significantly changed their periodicity during hypoxia compared with normoxia, we conclude that carotid chemoreceptors are not requisite for hypoxia-induced changes in periodic breathing. In addition, our observations in both groups of ponies during normoxia and hypoxia suggest that multiple mechanisms may lead to periodic oscillations in breathing.

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.

Changes in breathing pattern mediated by intrapulmonary CO2 receptors in chickens

1982 ◽  
Vol 52 (1) ◽  
pp. 162-167 ◽  
Author(s):  
R. D. Tallman ◽  
A. L. Kunz
Keyword(s):  
Carotid Body ◽  
Breathing Pattern ◽  
Complete Removal ◽  
Whole Body ◽  
Fixed Duration ◽  
Experimental Protocol ◽  
Phase Switching ◽  
Carotid Chemoreceptors ◽  
Carotid Bodies ◽  
Body Plethysmograph

The ventilation of unanesthetized tracheostomized chickens was measured using a whole-body plethysmograph. The inspired CO2 fraction was quickly manipulated between 0.05 and 0.0 in such a way as to limit the fresh air inspired to a fixed duration pulse preceded and followed by 5% CO2. As was previously shown with this experimental protocol [Tallman et al., Am. J. Physiol. 237 (Regulatory Integrative Comp. Physiol. 6): R260–R265, 1979], the duration of inspiration and expiration (TI and TE, respectively) was dependent on the timing, relative to inspiration, that the pulse of air arrived at the lung. To study the possible involvement of arterial chemoreceptors in this reflex, a method of denervating the carotid chemoreceptors in this reflex, a method of denervating the carotid bodies was developed. After denervation, the hyperpneic response to intravenous NaCN and 2–3 breaths of N2 was eliminated, indicating the complete removal of arterial chemoreflexes. When tested with the same protocol of CO2 inhalation following carotid body denervation, TI and TE were still dependent on the delay of the fresh air pulse. These experiments support the conclusion that intrapulmonary CO2 receptors (IPC) mediate the reflexes studied and provide evidence that IPC affect the phase-switching mechanisms on a breath-to-breath basis.

scholarly journals Simulated Sleep Apnea Alters Hydrogen Sulfide Regulation of Blood Flow and Pressure

2020 ◽  
Author(s):  
Adelaeda Barrera ◽  
Humberto Morales-Loredo ◽  
Joshua Garcia ◽  
Gisel Fregoso ◽  
Carolyn E. Pace ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hydrogen Sulfide ◽  
Sleep Apnea ◽  
Vascular Resistance ◽  
Carotid Body ◽  
Animal Studies ◽  
Mesenteric Arteries ◽  
Carotid Bodies ◽  
Inner Diameter ◽  
Induced Changes

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control rats. The goal of this study was to evaluate the contribution of IH-induced changes in CSE signaling to increased blood pressure and vascular resistance. We hypothesized that chronic IH exposure eliminates CSE regulation of blood pressure (BP) and vascular resistance. In rats instrumented with venous catheters, arterial telemeters, and flow probes on the main mesenteric artery, the CSE inhibitor DL-propargylglycine (PAG, 50 mg/kg/day i.v. for 5 days) increased BP in Sham rats but decreased BP in IH rats (in mmHg, Sham (n = 11): 114±4 to 131±6; IH (n = 8): 131±8 to 115±7 mmHg, p<0.05). PAG treatment increased mesenteric vascular resistance in Sham rats but decreased it in IH rats (Day 5/Day 1: Sham: 1.50 ± 0.07; IH: 0.85 ± 0.19, p<0.05). Administration of the ganglionic blocker hexamethonium (to evaluate SNS activity) decreased mesenteric resistance in PAG-treated Sham rats more than in saline-treated Sham rats or PAG-treated IH rats. CSE immunoreactivity in IH carotid bodies compared to those from Sham rats. However, CSE staining in small mesenteric arteries was less in arteries from IH compared to Sham rats but not different in larger arteries (inner diameter > 200 mm). These results suggest endogenous H2S regulates blood pressure and vascular resistance but this control is lost after IH exposure with decreased CSE expression in resistance size arteries. IH exposure concurrently increases carotid body CSE expression and relative SNS control of blood pressure suggesting both vascular and carotid body H2S generation contribute to blood pressure regulation.

Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI)

1998 ◽  
Vol 84 (1) ◽  
pp. 292-302 ◽  
Author(s):  
R. Gelfand ◽  
C. J. Lambertsen ◽  
J. M. Clark ◽  
E. Hopkin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adverse Effects ◽  
Exposure Time ◽  
Carotid Body ◽  
Exposure Limits ◽  
Peripheral Chemoreceptors ◽  
Human Organ ◽  
Ventilatory Responses ◽  
Before And After

Gelfand, R., C. J. Lambertsen, J. M. Clark, and E. Hopkin.Hypoxic ventilatory sensitivity in men is not reduced by prolonged hyperoxia (Predictive Studies V and VI). J. Appl. Physiol. 84(1): 292–302, 1998.—Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

Relative latency of responses of chemoreceptor afferents from aortic and carotid bodies

1980 ◽  
Vol 48 (2) ◽  
pp. 362-369 ◽  
Author(s):  
S. Lahiri ◽  
T. Nishino ◽  
E. Mulligan ◽  
A. Mokashi
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Carotid Body ◽  
Blood Gases ◽  
Unexpected Result ◽  
Blood Gas ◽  
Arterial Blood Gases ◽  
Carotid Chemoreceptors ◽  
Arterial Blood ◽  
Carotid Bodies

Discharges from aortic and carotid body chemoreceptor afferents were simultaneously recorded in 18 anesthetized cats to test the hypothesis that aortic chemoreceptors, because of their proximity to the heart, respond to changes in arterial blood gases before carotid chemoreceptors. We found that carotid chemoreceptor responses to the onset of hypoxia and hypercapnia, and to the intravenously administered excitatory drugs (cyanide, nicotine, and doxapram), preceded those of aortic chemoreceptors. Postulating that this unexpected result was due to differences in microcirculation and mass transport, we also investigated their relative speed of responses to changes in arterial blood pressure. The aortic chemoreceptors responded to decreases in arterial blood pressure before the carotid chemoreceptors, supporting the idea that the aortic body has microcirculatory impediments not generally present in the carotid body. These findings strengthened the concept that carotid bodies are more suited for monitoring blood gas changes due to respiration, whereas aortic bodies are for monitoring circulation.

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