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.

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.

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.

Effect of hypoxia on metabolic rate in awake ponies

1994 ◽  
Vol 76 (6) ◽  
pp. 2380-2385 ◽  
Author(s):  
M. J. Korducki ◽  
H. V. Forster ◽  
T. F. Lowry ◽  
M. M. Forster
Keyword(s):  
Metabolic Rate ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Pulmonary Ventilation ◽  
Time Dependent ◽  
Hypoxic Hypoxia ◽  
Arterial Pco2 ◽  
Breathing Room ◽  
Arterial Po2 ◽  
Transient Failure

To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobin, arterial PCO2 was 1.3 Torr above (P < 0.05) and 1.5 Torr (P < 0.05) below control levels after 30 min and 3 h, respectively. There were no significant (P > 0.10) changes in VO2 during either hypoxic or CO hypoxia. However, in 50% of the ponies, VO2, pulmonary ventilation, and rectal temperature increased and shivering was evident after 30 min of hypoxia. Peak values of pulmonary ventilation, VO2, and shivering occurred at approximately 2 h with a subsequent return toward control levels. We conclude that, in contrast to smaller mammals, acute hypoxia does not depress VO2 of ponies. The hypermetabolism and hyperthermia during chronic hypoxia in some ponies may reflect a transient failure in thermoregulation.

Role of the carotid body in hyperpnea of moderate exercise in goats

1982 ◽  
Vol 52 (5) ◽  
pp. 1216-1222 ◽  
Author(s):  
G. E. Bisgard ◽  
H. V. Forster ◽  
J. Mesina ◽  
R. G. Sarazin
Keyword(s):  
Metabolic Rate ◽  
Carotid Body ◽  
Blood Gases ◽  
Co2 Production ◽  
Sham Operation ◽  
Positive Interaction ◽  
Arterial Blood ◽  
Before And After ◽  
Response To Exercise ◽  
Rest And Exercise

In the present study the ventilatory response to exercise was measured in goats before and after carotid body excision (CBE) (n = 7) or sham operation (n = 1). Nine-minute periods of moderate treadmill walking were carried out under three conditions: 4.8 kph, 0% grade during normoxia and hypoxia (arterial O2 tension approximately 43 Torr) and 4.8 kph, 5% grade during normoxia. Ventilatory variables, metabolic rate, and arterial blood acid-base and blood gases were measured at 30-s intervals for the first 3 min and again during the 6th and 9th min of exercise. In normal goats during exercise in normoxia, ventilation changed in proportion to changes in metabolic rate resulting in arterial CO2 tension (PaCO2) and arterial pH (pHa) homeostasis throughout exercise. CBE resulted in nearly equivalent hypoventilation during steady-state rest and exercise (delta PaCO2 approximately equal to 5--7 Torr) during normoxia and loss of the positive interaction between hypoxia and exercise. There was also a significant disruption of PaCO2-pHa homeostasis during the first 30 s of exercise after CBE when PaCO2 was 3 Torr below rest and pHa was 0.03 units above rest. Our data indicate: 1) that the carotid chemoreceptors may contribute a similar proportional drive to breathe during rest and exercise; 2) that transient hyperventilation at the onset of exercise after CBE may indicate an important neural drive to breathe that is normally damped by intact peripheral chemoreceptors; and 3) that the mechanism linking ventilation to CO2 production remains intact after CBE.

Role of endothelin and endothelin A-type receptor in adaptation of the carotid body to chronic hypoxia

2002 ◽  
Vol 282 (6) ◽  
pp. L1314-L1323 ◽  
Author(s):  
J. Chen ◽  
L. He ◽  
B. Dinger ◽  
L. Stensaas ◽  
S. Fidone
Keyword(s):  
Carotid Body ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Critical Role ◽  
Immunocytochemical Staining ◽  
Type I ◽  
Type I Cells ◽  
I Cells

Chronic exposure in a low-Po 2 environment (i.e., chronic hypoxia, CH) elicits an elevated hypoxic ventilatory response and increased hypoxic chemosensitivity in arterial chemoreceptors in the carotid body. In the present study, we examine the hypothesis that changes in chemosensitivity are mediated by endothelin (ET), a 21-amino-acid peptide, and ETA receptors, both of which are normally expressed by O2-sensitive type I cells. Immunocytochemical staining showed incremental increases in ET and ETAexpression in type I cells after 3, 7, and 14 days of CH (380 Torr). Peptide and receptor upregulation was confirmed in quantitative RT-PCR assays conducted after 14 days of CH. In vitro recordings of carotid sinus nerve activity after in vivo exposure to CH for 1–16 days demonstrated a time-dependent increase in chemoreceptor activity evoked by acute hypoxia. In normal carotid body, the specific ETAantagonist BQ-123 (5 μM) inhibited 11% of the nerve discharge elicited by hypoxia, and after 3 days of CH the drug diminished the hypoxia-evoked discharge by 20% ( P < 0.01). This inhibitory effect progressed to 45% at day 9 of CH and to nearly 50% after 12, 14, and 16 days of CH. Furthermore, in the presence of BQ-123, the magnitude of the activity evoked by hypoxia did not differ in normal vs. CH preparations, indicating that the increased activity was the result of endogenous ET acting on an increasing number of ETA. Collectively, our data suggest that ET and ETA autoreceptors on O2-sensitive type I cells play a critical role in CH-induced increased chemosensitivity in the rat carotid body.

scholarly journals Mitochondrial Succinate Metabolism and Reactive Oxygen Species Are Important but Not Essential for Eliciting Carotid Body and Ventilatory Responses to Hypoxia in the Rat

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 840
Author(s):  
Agnieszka Swiderska ◽  
Andrew M. Coney ◽  
Abdulaziz A. Alzahrani ◽  
Hayyaf S. Aldossary ◽  
Nikolaos Batis ◽  
...  
Keyword(s):  
Carotid Body ◽  
Ex Vivo ◽  
Acute Hypoxia ◽  
Whole Body ◽  
Dimethyl Malonate ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Mitochondrial Ros ◽  
O2 Sensing

Reflex increases in breathing in response to acute hypoxia are dependent on activation of the carotid body (CB)—A specialised peripheral chemoreceptor. Central to CB O2-sensing is their unique mitochondria but the link between mitochondrial inhibition and cellular stimulation is unresolved. The objective of this study was to evaluate if ex vivo intact CB nerve activity and in vivo whole body ventilatory responses to hypoxia were modified by alterations in succinate metabolism and mitochondrial ROS (mitoROS) generation in the rat. Application of diethyl succinate (DESucc) caused concentration-dependent increases in chemoafferent frequency measuring approximately 10–30% of that induced by severe hypoxia. Inhibition of mitochondrial succinate metabolism by dimethyl malonate (DMM) evoked basal excitation and attenuated the rise in chemoafferent activity in hypoxia. However, approximately 50% of the response to hypoxia was preserved. MitoTEMPO (MitoT) and 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SKQ1) (mitochondrial antioxidants) decreased chemoafferent activity in hypoxia by approximately 20–50%. In awake animals, MitoT and SKQ1 attenuated the rise in respiratory frequency during hypoxia, and SKQ1 also significantly blunted the overall hypoxic ventilatory response (HVR) by approximately 20%. Thus, whilst the data support a role for succinate and mitoROS in CB and whole body O2-sensing in the rat, they are not the sole mediators. Treatment of the CB with mitochondrial selective antioxidants may offer a new approach for treating CB-related cardiovascular–respiratory disorders.

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