Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats

Hodges, Matthew R.; Martino, Paul; Davis, Suzanne E.; Opansky, C.; Pan, Lawrence; Forster, H. V.

doi:10.1152/japplphysiol.00645.2004

Cited by 67 publications

(65 citation statements)

References 34 publications

(37 reference statements)

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“…Electrophysiological recordings of in vitro preparations have shown that neurons in the retrotrapezoid nucleus, nucleus of the solitary tract, the medullary raphe nucleus (MRN), locus coeruleus, and the pre-Bötzinger complex (preBötzC) increase discharge frequency when the pH in the bathing solution is reduced (3,5,8,14,22,24). Studies in anesthetized preparations that either created a focal acidosis (FA) or assessed the effects of lesions on the hypercapnic ventilatory response also support the concept of widespread chemosensitivity in the medulla, pons, and cerebellum (11,18,32,33,35,36,37).While the in vivo data, under physiological conditions, suggest that chemoreceptors at multiple sites influence breathing, the observed ventilatory effects are not uniform, and the hyperpnea is small, with FA at a single site compared with the hyperpnea observed during a global brain acidosis. In the awake goat, microdialyzing (MD) hypercapnic mock cerebral spinal fluid (mCSF), which decreases extracellular fluid (ECF) pH by 0.018 in one area of the MRN, increases pulmonary ventilation (V I) by 12% (10), while a comparable global brain acidosis resulting from 2.5% inspired CO 2 increases breathing by 100% (10).…”

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“…In the awake goat, microdialyzing (MD) 50% CO2 at multiple sites within the medullary raphe increases pulmonary ventilation (V I), blood pressure, heart rate, and metabolic rate (V O2) (11), while MD in the rostral and caudal cerebellar fastigial nucleus has a stimulating and depressant effect, respectively, on these variables (17). In the anesthetized cat, the pre-Bötzinger complex (preBötzC), a hypothesized respiratory rhythm generator, increases phrenic nerve activity after an acetazolamide-induced acidosis (31,32).…”

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“…In the awake goat, microdialyzing (MD) hypercapnic mock cerebral spinal fluid (mCSF), which decreases extracellular fluid (ECF) pH by 0.018 in one area of the MRN, increases pulmonary ventilation (V I) by 12% (10), while a comparable global brain acidosis resulting from 2.5% inspired CO 2 increases breathing by 100% (10). However, when a FA is produced at two or three MRN sites, V I increases by 30%, due mostly to increases in tidal volume (VT) (11). This relatively small response to FA might, in part, be due to alkalosis at other chemosensitive sites during FA at one or a few sites.…”

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“…Furthermore, since ECF pH in the MRN decreases less than plasma pH during whole body hypercapnia (10), a third objective was to determine whether ECF pH in the preBötzC would also change less than plasma pH during whole body hypercapnia. Also, since, in the MRN (10,11) and CFN (17), the effects on breathing were solely due to a change in VT, a fourth objective was to determine if FA in the preBötzC would stimulate breathing through changes in VT or respiratory frequency (f). Finally, since FA in the MRN (10,11) and CFN (17) in the awake goat also had effects on metabolic rate (V O 2 ) and heart rate (HR), a fifth objective was to determine whether FA in the preBötzC would alter V O 2 and HR.…”

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Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

Krause¹,

Forster²,

Davis³

et al. 2009

Journal of Applied Physiology

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Krause KL, Forster HV, Davis SE, Kiner T, Bonis JM, Pan LG, Qian B. Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea. J Appl Physiol 106: 241-250, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.90547.2008There are widespread chemosensitive areas in the brain with varying effects on breathing. In the awake goat, microdialyzing (MD) 50% CO2 at multiple sites within the medullary raphe increases pulmonary ventilation (V I), blood pressure, heart rate, and metabolic rate (V O2) (11), while MD in the rostral and caudal cerebellar fastigial nucleus has a stimulating and depressant effect, respectively, on these variables (17). In the anesthetized cat, the pre-Bötzinger complex (preBötzC), a hypothesized respiratory rhythm generator, increases phrenic nerve activity after an acetazolamide-induced acidosis (31, 32). To gain insight into the effects of focal acidosis (FA) within the preBötzC during physiological conditions, we tested the hypothesis that FA in the preBötzC during wakefulness would stimulate breathing, by increasing respiratory frequency (f). Microtubules were bilaterally implanted into the preBötzC of 10 goats. Unilateral MD of mock cerebral spinal fluid equilibrated with 6.4% CO2 did not affect V I, tidal volume (VT), or f. Unilateral MD of 25 and 50% CO2 significantly increased V I and f by 10% (P Ͻ 0.05, n ϭ 10, 17 trials), but VT was unaffected. Bilateral MD of 6.4, 25, or 50% CO2 did not significantly affect V I, VT, or f (P Ͼ 0.05, n ϭ 6, 6 trials). MD of 80% CO2 caused a 180% increase in f and severe disruptions in airflow (n ϭ 2). MD of any level of CO2 did not result in any significant changes in mean arterial blood pressure, heart rate, or V O2. Thus the data suggest that the preBötzC area is chemosensitive, but the responses to FA at this site are unique compared with other chemosensitive sites.breathing; chemosensitivity CENTRAL RESPIRATORY CO 2 /H ϩ chemoreception has been traditionally attributed to sites at or near the ventrolateral medullary surface (16,24,27). However, studies over the last 15-20 yr indicate that the ventrolateral medullary surface is not the sole CO 2 /H ϩ -sensitive area (1-3, 5, 15, 17, 21, 24, 31, 32). Electrophysiological recordings of in vitro preparations have shown that neurons in the retrotrapezoid nucleus, nucleus of the solitary tract, the medullary raphe nucleus (MRN), locus coeruleus, and the pre-Bötzinger complex (preBötzC) increase discharge frequency when the pH in the bathing solution is reduced (3,5,8,14,22,24). Studies in anesthetized preparations that either created a focal acidosis (FA) or assessed the effects of lesions on the hypercapnic ventilatory response also support the concept of widespread chemosensitivity in the medulla, pons, and cerebellum (11,18,32,33,35,36,37).While the in vivo data, under physiological conditions, suggest that chemoreceptors at multiple sites influence breathing, the observed ventilatory effects are not uniform, and the hyperpnea is small, with FA at a single si...

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confidence: 91%

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confidence: 91%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

Krause¹,

Forster²,

Davis³

et al. 2009

Journal of Applied Physiology

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Central respiratory chemoreception

Guyenet¹,

Stornetta²,

Bayliss³

2010

J of Comparative Neurology

210

187

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Summary By definition central respiratory chemoreceptors (CRCs) are cells that are sensitive to changes in brain PCO2 or pH and contribute to the stimulation of breathing elicited by hypercapnia or metabolic acidosis. CO2 most likely works by lowering pH. The pertinent proton receptors have not been identified and may be ion channels. CRCs are probably neurons but may also include acid-sensitive glia and vascular cells that communicate with neurons via paracrine mechanisms. Retrotrapezoid nucleus (RTN) neurons are the most completely characterized CRCs. Their high sensitivity to CO2 in vivo presumably relies on their intrinsic acid-sensitivity, excitatory inputs from the carotid bodies and brain regions such as raphe and hypothalamus, and facilitating influences from neighboring astrocytes. RTN neurons are necessary for the respiratory network to respond to CO2 during the perinatal period and under anesthesia. In conscious adults, RTN neurons contribute to an unknown degree to the pH-dependent regulation of breathing rate, inspiratory and expiratory activity. The abnormal prenatal development of RTN neurons probably contributes to the congenital central hypoventilation syndrome. Other CRCs presumably exist but the supportive evidence is less complete. The proposed locations of these CRCs are the medullary raphe, the nucleus tractus solitarius, the ventrolateral medulla, the fastigial nucleus and the hypothalamus. Several wake-promoting systems (serotonergic and catecholaminergic neurons, orexinergic neurons) are also putative CRCs. Their contribution to central respiratory chemoreception may be behavior-dependent or vary according to the state of vigilance.

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Central Chemoreceptors: Locations and Functions

Nattie¹,

Li²

2012

Comprehensive Physiology

201

139

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Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H+ detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H+, serves to detect and integrate information on 1) alveolar ventilation (arterial PCO2), 2) brain blood flow and metabolism and 3) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone) and arousal. In addition, central chemoreception provides a tonic ‘drive’ (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air vs. water breathing, homeothermy, sleep, optimization of the work of breathing with the ‘ideal’ arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function.

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Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats

Cited by 67 publications

References 34 publications

Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

Central respiratory chemoreception

Central Chemoreceptors: Locations and Functions

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