Hypoxic respiratory responses attenuated by ablation of the cerebellum or fastigial nuclei

Xu, Fadi; Owen, Joseph W.; Frazier, Donald T.

doi:10.1152/jappl.1995.79.4.1181

Cited by 34 publications

(34 citation statements)

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“…Therefore, DVH could be the results of diminishing the carotid chemoreceptor-mediated excitatory response and/or strengthening hypoxic central depression. Intracarotid injection of cyanide or doxapram has been demonstrated to elevate ventilation mainly via activating peripheral chemoreceptors (25,36,43). Our data that the ventilatory responses to these selective stimuli were inhibited by Ova exposure convincingly demonstrated that DVH was generated, at least partially, by attenuating the carotid chemoreceptor-mediated respiratory response.…”

Section: Dvh In Ova Guinea Pigs Involves At Least Partially the Supsupporting

confidence: 59%

“…To test the effect of Ova exposure on the peripheral chemoreceptors-mediated ventilatory responses, both groups of animals were randomly exposed to intracarotid injection of sodium cyanide (20 g) and doxapram (2 mg) 5 min after pure N 2 exposure. These stimuli have been demonstrated to augment ventilation predominately via activating peripheral chemoreceptors (25,36,43) without systemic hypoxia. Inhalation of hypercapnic gas mixtures (7% CO 2-21% O2-balance N2) for 5 min was subsequently applied to stimulate central chemoreceptors.…”

Section: Methodsmentioning

confidence: 99%

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Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Zhuang²,

Zhou³

et al. 2005

Journal of Applied Physiology

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tients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH), but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 min, 5 days/wk, for 2 wk. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O 2 and CO2 tensions, but it attenuated the ventilatory response to hypoxia (10 breaths of pure N 2) by 65% (P Ͻ 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 g) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P Ͻ 0.05) and 74% (P Ͻ 0.05), respectively. In contrast, Ova exposure failed to affect the ventilatory response to CO 2 (7% CO2-21% O2-balance N2 for 5 min; P Ͼ 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C fibers (PCFs) with right atrial injection of capsaicin (5 g) was markedly increased in the Ova-sensitized group (5.02 Ϯ 1.56 s), compared with the control group (1.82 Ϯ 0.45 s; P Ͻ 0.05). These results suggest that Ova sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCF-mediated ventilatory inhibition. carotid body; bronchopulmonary C fibers; hypoxia; capsaicin; inflammation RESPIRATORY FAILURE FROM ASTHMA is a common clinical symptom and a primary cause of high mortality. A study through a period of 7 yr indicated that 68% of asthmatic patients had two or more episodes of respiratory failure that led to an ϳ10% death rate (30). Ventilatory arrest in the near-fatal nature of the exacerbations is dominant compared with cardiac arrest (26). It is generally recognized that patients with chronic bronchial asthma have a depressed ventilatory response to hypoxia (DVH) that may contribute to the respiratory failure (4, 11, 14 -16, 21, 33, 38), although an absence (27) of DVH or an increase of ventilatory response to hypoxia (20) was also reported. Hudgel and Weil (14,15) first reported a severe DVH in asthmatic individuals in 1974. Subsequent studies confirmed this observation and further indicated that the amplitude of minute ventilation (V E) in response to progressive isocapnic hypoxia was significantly attenuated in both young and adult patients compared with age-matched normal subjects (4,11,16,21,33,38). A severely diminished hypoxic perception was also found in asthmatic patients; a typical example is that the patients who had asthma displayed cyanosis but had no dyspnea at all (21). This blunted hypoxic perception could impair the behavioral control of breathing and worsen hypoxemia by reducing ventilatory augmentation. To date, the pathophysiological mechanisms underlying DVH i...

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Section: Dvh In Ova Guinea Pigs Involves At Least Partially the Supsupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Zhuang²,

Zhou³

et al. 2005

Journal of Applied Physiology

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“…Also in anesthetized mammals, electrical or chemical stimulation of the CFN increases breathing (30,218,219,352,357,358). Moreover ablation of the CFN attenuates the respiratory responses to hypercapnia and hypoxia (360,361). Finally, the CFN contains respiratorymodulated neurons responding to hypercapnia and hypoxia (145,219,359).…”

Section: Role Of the Cerebellummentioning

confidence: 99%

Control of Breathing During Exercise

Forster

Haouzi

Dempsey

2012

Comprehensive Physiology

192

203

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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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“…Deep cerebellar nuclei project to more rostral sites, including the midbrain and thalamus (Person et al, 1986); a major projection directly inputs to the rostral ventral respiratory cell group in rodents (Gaytan and Pasaro, 1998). The fastigial nuclei play critical roles in mediating compensatory responses to low blood pressure (Lutherer et al, 1983), and responses to hypoxia (Xu et al, 1995), and show neuronal responsivity to CO 2 (Xu and Frazier, 1997). Dysregulation of fastigial output has the potential to lead to aberrant sympathetic and parasympathetic control, resulting in such characteristics of CCHS as the absence of "dipping" of blood pressure during sleep , undampened blood pressure responses to syncope to postural changes or thoracic pressure manipulations (Weese-Mayer et al, 2001), and diminished heart rate variation to cold pressor challenges (Kim et al, 2002).…”

Section: Cerebellar Regionsmentioning

confidence: 99%

Neuroanatomic deficits in congenital central hypoventilation syndrome

Kumar

Macey

Woo

et al. 2005

J of Comparative Neurology

100

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Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

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Hypoxic respiratory responses attenuated by ablation of the cerebellum or fastigial nuclei

Cited by 34 publications

References 0 publications

Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs

Control of Breathing During Exercise

Neuroanatomic deficits in congenital central hypoventilation syndrome

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