Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe

Hodges, Matthew R.; Opansky, C.; Qian, Baogang; Davis, Suzanne E.; Bonis, Joshua M.; Krause, Katherine; Pan, Lawrence; Forster, H. V.

doi:10.1152/japplphysiol.01011.2004

Cited by 38 publications

(42 citation statements)

References 25 publications

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“…Data obtained from a variety of experimental approaches and different animal models, including genetically modified animals [24,28], support a role for the medullary raphe and specifically 5-HT neurons in central chemoreception [7,22,23]. Focal acidosis of the medullary raphe elicited increased ventilation in adult goats, which was attenuated after CB denervation [25]. These results suggest that peripheral chemoreceptors may provide facilitatory inputs for modulating central CO 2 sensitivity [4,25].…”

mentioning

confidence: 79%

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Silva

Giusti

Benedetti

et al. 2011

Pflugers Arch - Eur J Physiol

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Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in the respiratory control network. However, it is not known whether ROb 5-HT neurons play a role in the functional interdependence between central and peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT neurons in the ventilatory responses to CO₂ and their putative involvement in the central-peripheral CO₂ chemoreceptor interaction in unanaesthetised rats. We used a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (V (E)), body temperature and the arterial blood gases were measured before, during and after a hypercapnic challenge (7% CO₂). The lesion of ROb 5-HT neurons alone (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline V (E) during normocapnic condition. Killing ROb 5-HT neurons (CB intact) significantly decreased the ventilatory response to hypercapnia (p < 0.05). The reduction in CO₂ sensitivity was approximately 15%. When ROb 5-HT neurons lesion was combined with CBR (anti-SERT-SAP+CBR), the V (E) response to hypercapnia was further decreased (-31.2%) compared to the control group. The attenuation of CO₂ sensitivity was approximately 30%, and it was more pronounced than the sum of the individual effects of central (ROb lesion; -12.3%) or peripheral (CBR; -5.5%) treatments. Our data indicate that ROb 5-HT neurons play an important role in the CO₂ drive to breathing and may act as an important element in the central-peripheral chemoreception interaction to CO₂ responsiveness.

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mentioning

confidence: 79%

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Silva

Giusti

Benedetti

et al. 2011

Pflugers Arch - Eur J Physiol

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“…The sensory responses are fast enabling detection of breath to breath oscillation in arterial blood gases. Moreover, as indicated by the severe hypoventilation that occurs after CBD, the tonic activity of the carotid body provides a major stimulus for eupneic breathing (48,51,167,265,285).…”

Section: Carotid Afferent Mediation Of the Exercise Hyperpneamentioning

confidence: 99%

Control of Breathing During Exercise

Forster

Haouzi

Dempsey

2012

Comprehensive Physiology

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During exercise by healthy mammals, alveolar ventilation and alveolar-capillary diffusion increase in proportion to the increase in metabolic rate to prevent PaCO2 from increasing and PaO2 from decreasing. There is no known mechanism capable of directly sensing the rate of gas exchange in the muscles or the lungs; thus, for over a century there has been intense interest in elucidating how respiratory neurons adjust their output to variables which can not be directly monitored. Several hypotheses have been tested and supportive data were obtained, but for each hypothesis, there are contradictory data or reasons to question the validity of each hypothesis. Herein, we report a critique of the major hypotheses which has led to the following conclusions. First, a single stimulus or combination of stimuli that convincingly and entirely explains the hyperpnea has not been identified. Second, the coupling of the hyperpnea to metabolic rate is not causal but is due to of these variables each resulting from a common factor which link the circulatory and ventilatory responses to exercise. Third, stimuli postulated to act at pulmonary or cardiac receptors or carotid and intracranial chemoreceptors are not primary mediators of the hyperpnea. Fourth, stimuli originating in exercising limbs and conveyed to the brain by spinal afferents contribute to the exercise hyperpnea. Fifth, the hyperventilation during heavy exercise is not primarily due to lactacidosis stimulation of carotid chemoreceptors. Finally, since volitional exercise requires activation of the CNS, neural feed-forward (central command) mediation of the exercise hyperpnea seems intuitive and is supported by data from several studies. However, there is no compelling evidence to accept this concept as an indisputable fact.

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“…CBD clearly induces severe hypoventilation during eupnea (Hodges et al, 2005), but partial lesioning of intracranial chemoreceptor sites has minimal effect on eupneic breathing (Forster et al, 1998;Hodges et al, 2004b;Nattie and Li, 2006). It is unclear whether this difference could be due to the fact that CBD eliminates the entire carotid complex, but the lesions in the brain only eliminate a small portion of the central chemoreceptors.…”

Section: Chronic Effects On Breathing Of Cerebellar Lesionsmentioning

confidence: 99%

The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats

Martino

Davis

Opansky

et al. 2007

Respiratory Physiology & Neurobiology

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The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO 2 -H + sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N = 9) for injection (0.5-10 μl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO 2 -H + sensitivity did not differ significantly (P > 0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic Pa CO 2 (P > 0.10). The coefficient of variation of eupneic Pa CO 2 was 4.0±0.6 and 3.7±0.4% over the 2 weeks before and after the lesion, respectively. CO 2 -H + sensitivity expressed as inspired ventilation/Pa CO 2 decreased from 2.15±0.17 pre-lesion to 1.58±0.26 l/(min mmHg) 3-6 days post-lesion (P < 0.02, −27%). There was no significant (P > 0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P < 0.05) the day-to-day variability of this index by nearly 100%. When CO 2 sensitivity was expressed as elevated inspired CO 2 /room air V̇I, values at 7%, but not 3 and 5% inspired CO 2 , were reduced and more variable (P < 0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia.

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Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe

Cited by 38 publications

References 25 publications

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Serotonergic neurons in the nucleus raphe obscurus contribute to interaction between central and peripheral ventilatory responses to hypercapnia

Control of Breathing During Exercise

The cerebellar fastigial nucleus contributes to CO2-H+ ventilatory sensitivity in awake goats

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