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Pulmonary mechanosensory receptors provide important inputs to the respiratory center for control of breathing. However, what is known about their structure–function relationship is still limited. In these studies, we explored this relationship comparing bronchopulmonary slowly adapting receptor (SAR) units in rabbits and rats. In morphological studies, sensory units in tracheobronchial smooth muscle labeled with anti‐Na+/K+‐ATPase (α3 subunit) were found to be larger in the rabbit. Since larger structures may result from increased receptor size or more numerous receptors, further examination showed receptor size was the same in both species, but more receptors in a structure in rabbits than rats, accounting for their larger structure. In functional studies, SAR units were recorded electrically in anesthetized, open‐chest, and artificially ventilated animals and responses to lung inflation were compared at three different constant airway pressures (10, 20, and 30 cmH2O). At each level of the inflation, SAR discharge frequencies were found to be higher in rabbits than rats. We conclude that a relatively larger number of receptors in a sensory unit may be responsible for higher SAR activities in rabbit SAR units. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary mechanosensory receptors provide important inputs to the respiratory center for control of breathing. However, what is known about their structure–function relationship is still limited. In these studies, we explored this relationship comparing bronchopulmonary slowly adapting receptor (SAR) units in rabbits and rats. In morphological studies, sensory units in tracheobronchial smooth muscle labeled with anti‐Na+/K+‐ATPase (α3 subunit) were found to be larger in the rabbit. Since larger structures may result from increased receptor size or more numerous receptors, further examination showed receptor size was the same in both species, but more receptors in a structure in rabbits than rats, accounting for their larger structure. In functional studies, SAR units were recorded electrically in anesthetized, open‐chest, and artificially ventilated animals and responses to lung inflation were compared at three different constant airway pressures (10, 20, and 30 cmH2O). At each level of the inflation, SAR discharge frequencies were found to be higher in rabbits than rats. We conclude that a relatively larger number of receptors in a sensory unit may be responsible for higher SAR activities in rabbit SAR units.

Inhalation of nebulized furosemide has been shown to alleviate breathlessness provoked experimentally in health and disease; however, it remains unclear whether the efficacy of nebulized furosemide on breathlessness is dose-dependent. We tested the hypothesis that inhaled nebulized furosemide would be associated with a dose-dependent relief of breathlessness during exercise testing in the setting of abnormal restrictive constraints on tidal volume (VT) expansion. In a randomized, double-blind, crossover study, 24 healthy men aged 25.3 ± 1.2 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test in the setting of external thoracic restriction via chest wall strapping to reduce vital capacity by ~20% following single-dose inhalation nebulized furosemide (40 and 120 mg) and 0.9% saline. Compared with 0.9% saline, neither 40 nor 120 mg of inhaled nebulized furosemide had an effect on ratings of perceived breathlessness during exercise or an effect on cardiometabolic, ventilatory, breathing pattern, or dynamic operating lung volume responses during exercise. Urine production rate, the percentage of participants reporting an “urge to urinate” and the intensity of perceived “urge to urinate” were all significantly greater after inhaling the 120 mg furosemide solution compared with both 0.9% saline and 40 mg furosemide solutions. We concluded that, under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 and 120 mg did not alleviate breathlessness during exercise in healthy men.

Inhalation of nebulized furosemide has been shown to alleviate breathlessness provoked experimentally in health and disease; however, it remains unclear whether the efficacy of nebulized furosemide on breathlessness is dose-dependent. We tested the hypothesis that inhaled nebulized furosemide would be associated with a dose-dependent relief of breathlessness during exercise testing in the setting of abnormal restrictive constraints on tidal volume (VT) expansion. In a randomized, double-blind, crossover study, 24 healthy men aged 25.3 ± 1.2 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test in the setting of external thoracic restriction via chest wall strapping to reduce vital capacity by ~20% following single-dose inhalation nebulized furosemide (40 and 120mg) and 0.9% saline. Compared with 0.9% saline, neither 40 nor 120mg of inhaled nebulized furosemide had an effect on ratings of perceived breathlessness during exercise or an effect on cardiometabolic, ventilatory, breathing pattern, or dynamic operating lung volume responses during exercise. Urine production rate, the percentage of participants reporting an "urge to urinate" and the intensity of perceived "urge to urinate" were all significantly greater after inhaling the 120mg furosemide solution compared with both 0.9% saline and 40mg furosemide solutions. We concluded that, under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 and 120mg did not alleviate breathlessness during exercise in healthy men. [ABSTRACT FROM AUTHOR]

Abstract: The dorsal periaqueductal gray (dPAG) is an essential neural component for central integration of defense behavior and associated autonomic regulation. Electrical and chemical stimulation of this region results in a significant decrease of inspiratory (Ti) and expiratory (Te) breathing durations. In the present study it was hypothesized that breath timing changes elicited by dPAG activation would modulate respiratory load compensation volume–timing reflexes. The effect of dPAG activation of breathing pattern was investigated using chemical stimulation with microinjection of the excitatory amino acid D,L-homocysteic acid (DLH) or disinhibition with GABAA (γ-aminobutyric acid) receptor antagonist bicuculline (BIC) in urethane-anesthetized, spontaneously breathing rats. Volume–timing reflexes were studied using inspiratory and expiratory occlusion before and after DLH or BIC dPAG activation. Both BIC and DLH activation of the dPAG significantly increased breathing frequency. Inspiratory occlusion significantly increased Ti before dPAG activation and DLH and BIC potentiated the relative increase in Ti during occlusion. BIC elicited a greater increase in inspiratory occlusion Ti than DLH. Inspiratory occlusion alone also significantly increased diaphragm EMG activity and this response was potentiated with dPAG activation. Expiratory occlusion significantly increased Te and DLH and BIC potentiated the relative increase in Te during expiratory occlusion. These results suggest that dPAG activation modulates the respiratory neural network, resulting in an increased respiratory drive and a decrease in volume–timing reflex sensitivity. [Copyright &y& Elsevier]

• Lower airway innervation is required for mechanically- and chemically-induced cough. • Lower airway vagal volume-related sensory feedback is key for cough excitability. • Recurrent laryngeal nerve innervation is not sufficient to initiate lower airway cough. Recurrent laryngeal afferent fibers are primarily responsible for cough in response to mechanical or chemical stimulation of the upper trachea and larynx in the guinea pig. Lower airway slowly adapting receptors have been proposed to have a permissive effect on the cough reflex. We hypothesized that vagotomy below the recurrent laryngeal nerve branch would depress mechanically or chemically induced cough. In anesthetized, bilaterally thoracotomized, artificially ventilated cats, thoracic vagotomy nearly eliminated cough induced by mechanical stimulation of the intrathoracic airway, significantly depressed mechanically stimulated laryngeal cough, and eliminated capsaicin-induced cough. These results support an important role of lower airway sensory feedback in the production of tracheobronchial and laryngeal cough in the cat. Further, at least some of this feedback is due to excitation from pulmonary volume-sensitive sensory receptors. [ABSTRACT FROM AUTHOR]

Abstract: Peri-stimulus time histograms (PSTHs) reveal the temporal distribution of action potentials, averaged over many stimulus presentations. PSTHs have been used as model responses to solve the classification problem, in which a single response (i.e., spike train) is assigned to one of a set of response models evoked by a set of stimuli. In this study, we developed and applied a sparse firing frequency-based method to classify individual spike trains of slowly adapting pulmonary stretch receptors (SARs). Extracellularly recorded individual SAR spike trains were evoked by one of three different lung inflation volumes in anesthetized, paralyzed adult male New Zealand White rabbits. Three different PSTH-based firing frequency response models (i.e., one for each stimulus) were constructed from two-thirds of the responses to the 600 inflations presented at each volume, while the remaining one-third were used as responses to be classified. An instantaneous firing frequency representation of each remaining “test response” was computed from their individual spike trains, using one of two forms: sparse and filled. The sparse format assigned instantaneous firing rate values only in bins that contained spikes, while the filled format assigned values to intervening bins too. Classification was performed by computing the Euclidean distance between the response spike trains and the three PSTH-based models using both sparse and filled representations. When comparing the two representations with regard to classification accuracy, we found that the sparse representation does not diminish performance appreciably, while reducing computational burden significantly. [Copyright &y& Elsevier]

Inhalation of nebulized furosemide has been shown to alleviate breathlessness provoked experimentally in health and disease; however, it remains unclear whether the efficacy of nebulized furosemide on breathlessness is dose-dependent. We tested the hypothesis that inhaled nebulized furosemide would be associated with a dose-dependent relief of breathlessness during exercise testing in the setting of abnormal restrictive constraints on tidal volume (V T ) expansion. In a randomized, double-blind, crossover study, 24 healthy men aged 25.3 ± 1.2 years (mean ± SE) completed a symptom-limited constant-load cycle endurance exercise test in the setting of external thoracic restriction via chest wall strapping to reduce vital capacity by ~20% following single-dose inhalation nebulized furosemide (40 and 120 mg) and 0.9% saline. Compared with 0.9% saline, neither 40 nor 120 mg of inhaled nebulized furosemide had an effect on ratings of perceived breathlessness during exercise or an effect on cardiometabolic, ventilatory, breathing pattern, or dynamic operating lung volume responses during exercise. Urine production rate, the percentage of participants reporting an "urge to urinate" and the intensity of perceived "urge to urinate" were all significantly greater after inhaling the 120 mg furosemide solution compared with both 0.9% saline and 40 mg furosemide solutions. We concluded that, under the experimental conditions of this study, inhalation of nebulized furosemide at doses of 40 and 120 mg did not alleviate breathlessness during exercise in healthy men.