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Upper airways (UA) are an organic component of the respiratory tract, they serve to respiration, respiratory tract protection and defense, phonation, deglutition, etc. The functions of UA are regulated by motor control of the oral, pharyngeal, and laryngeal muscles.

Methods that had been applied to study central neuronal circuits regulating cough and respiratory reflexes so far rely on recording performed in vivo, ex vivo, micro injecting and lesion methods. Based on the available data it is clear that this network is complicated, multilevel, holarchical, undergoing reconfiguration under afferent inputs. For many students and researchers it is complicated to get a virtual spatial image of these cooperating neuronal populations. The project was aimed to create graphical three-dimensional computer model of the brainstem using environment MATLAB and the matrix algebra to visualize neuron localization within the brainstem. Relevant data for the model had been taken from recent and also former research papers published in particular areas. This model may help scientists to visualize groups of neurons, help them to find targets for microinjecting or lesion studies together with stereotaxic positioning. The model is upgradeable and highly flexible for future use, research and teaching applications in MATLAB environment. MATLAB is a high-level language and interactive environment that enables you to perform computationally intensive tasks faster than with traditional programming languages

Introduction: It is generally acknowledged that there is a correlation between the incidence of ultraviolet burden diseases and an overexposure of the body to ultraviolet radiation (UVR). The main goal of our study was to determine the personal protection of students against the harmful effects of UVR. Methods: We performed a questionnaire study of UVR in years 2005 and 2008 at 2 Slovak universities - Comenius University in Bratislava, the Jessenius Faculty of Medicine in Martin (JFMED) and the University of Žilina (UŽ). Results: The study includes 478 university students, 403 from JFMED and 75 from UŽ; 315 respondents in 2005 and 163 in 2008. The number of students avoiding solaria increased in 2008 (p<0.001) compared to 2005 because of the reduction of those attending solaria occasionally (p<0.001). A low number of regular users of solaria in 2005 did not decrease in 2008 significantly. The proportion of students not familiar with the term "skin photo-type" was not significantly different in 2005 and 2008. However, the number of those who knew their skin type rose in 2008 (p<0.05) compared to the number in 2005. No statistically significant improvement in the protection of students against UVR (the ratios of respondents using sunscreens, wearing sunglasses, and wearing the hat and clothes) was found in 2008 compared to 2005. Conclusions: This study showed the particular types of personal protection of university students, future doctors and bioengineers. Higher level of students' awareness against the harmful effects of UVR and improved safety behaviour related to UVR exposure was proved. The study brings new insights on the surveillance and protection against the harmful effects of UVR in university students. [ABSTRACT FROM AUTHOR]

Effects of sequential increase in airway resistance: no, low (5 kPa.s/l), high (24 kPa.s/l), and complete block in the inspiratory or expiratory phase of mechanically induced cough on the cough motor pattern were studied in 16 anesthetized (pentobarbital) spontaneously breathing cats (3.70±0.15 kg, 11♂, 5♀). Esophageal pressure and electromyographic activities of the diaphragm during inspiration and abdominal muscles during expiration were analyzed. No significant changes in the number of coughs occurred. Inspiratory occlusion caused a prolongation of cough inspiratory phase, cough inspiratory diaphragm activity, and all cough-related activity. Inspiratory occlusion along with high resistance increased inspiratory esophageal pressure amplitude, total cough cycle duration and the time between maximum activity of the diaphragm and abdominal muscles. High expiratory resistance and occlusion resulted in increased cough expiratory esophageal pressure amplitude, a longer active portion of cough expiration, and cough abdominal activity. Expiratory occlusion also prolonged cough expiratory phase, all cough activity, and total cough cycle. Significantly increased airway resistance and occlusion induce secondary, in addition to mechanical, changes in cough by significantly modulating the generated cough motor pattern. A certain level of resistance appears to be successfully compensated, resulting in minimal changes in coughing characteristics, including expiratory airflow and the rising time of the airflow. Afferent feedback from the respiratory tract, particularly volume feedback, represents a significant factor in modulating cough, mainly under various pathological conditions in the respiratory system., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Codeine was microinjected into the area of the Kölliker-Fuse nucleus and the adjacent lateral parabrachial nucleus, within the pontine respiratory group in 8 anesthetized cats. Electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD), esophageal pressures (EP), and blood pressure were recorded and analyzed during mechanically induced tracheobronchial cough. Unilateral microinjections of 3.3 mM codeine (3 injections, each 37 ± 1.2 nl) had no significant effect on the cough number. However, the amplitudes of the cough ABD EMG, expiratory EP and, to a lesser extent, DIA EMG were significantly reduced. There were no significant changes in the temporal parameters of the cough. Control microinjections of artificial cerebrospinal fluid in 6 cats did not show a significant effect on cough data compared to those after codeine microinjections. Codeine-sensitive neurons in the rostral dorsolateral pons contribute to controlling cough motor output, likely through the central pattern generator of cough., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An anesthetized cat animal model was used to evaluate changes in cough and swallow after a small midline upper abdominal incision (laparotomy). Two additional conditions were tested: sealing the laparotomy with gentle suctioning via a small cannula, and subsequent closure of the abdominal wall with suture. These abdominal wall manipulations resulted in no changes in the cough reflex, but produced higher motor drive to pharyngeal musculature (thyropharyngeus and geniohyoid muscles) during swallow. Swallow-breathing coordination phase preference shifted towards swallow occurring more during the inspiratory phase. There were no significant changes in cough motor pattern, or cough and swallow number and temporal features. The respiratory changes were limited to reduced inspiratory motor drive to the diaphragm. The results are consistent with an important role of sensory feedback from the abdominal wall in regulation of swallow motor pattern. The level of reflex modulation may depend on the extent of injury and likely on its position in the abdomen., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bicuculline and saclofen were microinjected into the rostral (rNTS) and caudal nucleus of the solitary tract (cNTS) in 17 anesthetized cats. Electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD), esophageal pressures (EP), and blood pressure were recorded and analyzed. Bilateral microinjections of 1 mM bicuculline in the rNTS significantly reduced the number of coughs (CN), amplitudes of DIA and ABD EMG, inspiratory and expiratory EP, and prolonged the duration of the cough expiratory phase (CTE) as well as the total cough cycle duration (CTtot). Bilateral microinjections of 2 mM saclofen reduced only cough expiratory efforts. Bilateral microinjection of bicuculline in the cNTS significantly reduced CN and amplitudes of ABD EMG and elongated CTE and CTtot. Bilateral microinjections of saclofen in cNTS had no significant effect on analyzed cough parameters. Our results confirm a different GABAergic inhibitory system in the rNTS and cNTS acting on mechanically induced cough in cats., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Effective cough requires a significant increase in lung volume used to produce the shear forces on the airway to clear aspirated material. This increase in tidal volume during cough, along with an increase in tidal frequency during bouts of paroxysmal cough produces profound hyperventilation and thus reduces arterial CO 2 . While there are several reports in the literature regarding the effects of hypercapnia, hyperoxia, and hypoxia on cough, there is little research quantifying the effects of hypocapnia on the cough reflex. We hypothesized that decreased CO 2 would enhance coughing. In 12 spontaneously breathing adult male cats, we compared bouts of prolonged mechanically stimulated cough, in which cough induced hyperventilation (CHV) was allowed to occur, with isocapnic cough trials where we maintained eupneic end-tidal CO 2 by adding CO 2 to the inspired gas. Isocapnia slightly increased cough number and decreased esophageal pressures with no change in EMG magnitudes or phase durations. The cough-to-eupnea transition was also analyzed between CHV, isocapnia, and a third group of animals that were mechanically hyperventilated to apnea. The transition to eupnea was highly sensitive to added CO 2 , and CHV apneas were much shorter than those produced by mechanical hyperventilation. We suggest that the cough pattern generator is relatively insensitive to CHV. In the immediate post-cough period, the appearance of breathing while CO 2 is very low suggests a transient reduction in apneic threshold following a paroxysmal cough bout., (Copyright © 2022. Published by Elsevier B.V.)

We employed computational modeling to investigate previously conducted experiments of the effect of vagal afferent modulation on the cough reflex in an anesthetized cat animal model. Specifically, we simulated unilateral cooling of the vagus nerve and analyzed characteristics of coughs produced by a computational model of brainstem cough/respiratory neuronal network. Unilateral vagal cooling was simulated by a reduction of cough afferent input (corresponding to unilateral vagal cooling) to the cough network. All these attempts resulted in only mild decreases in investigated cough characteristics such as cough number, amplitudes of inspiratory and expiratory cough efforts in comparison with experimental data. Multifactorial alterations of model characteristics during cough simulations were required to approximate cough motor patterns that were observed during unilateral vagal cooling in vivo. The results support the plausibility of a more complex NTS processing system for cough afferent information than has been proposed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABA A receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABA A receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors. NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABA A receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.

Unilateral and bilateral cooling and bilateral transsection of the superior laryngeal nerve (SLN) were employed to modulate mechanically induced tracheobronchial (TB) and laryngopharyngeal (LPh) cough in 12 anesthetized cats. There was little effect of SLN block or cut on TB. Bilateral SLN cooling reduced the number of LPh (<50 %, p < 0.05), amplitudes of diaphragm EMG activity (<55 %, p < 0.05), and cough expiratory efforts (<40 %, p < 0.01) during LPh. Effects after unilateral SLN cooling were less pronounced. Temporal analysis of LPh showed only shortening of diaphragm and abdominal muscles burst overlap in the inspiratory-expiratory transition after unilateral SLN cooling. Bilateral cooling reduced both expiratory phase and total cough cycle duration. There was no significant difference in the average effects of cooling left or right SLN on LPh or TB as well as no differences in contralateral and ipsilateral diaphragm and abdominal EMG amplitudes. Our results show that reduced afferent drive in the SLN markedly attenuates LPh with virtually no effect on TB., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cough is a vital airway reflex that keeps the respiratory tract wisely protected. It is also a sign of many diseases of the respiratory system and it may become a disease in its own right. Even though the efficacy of antitussive compounds is extensively studied in animal models with promising results, the treatment of pathological cough in humans is insufficient at the moment. The limited translational potential of animal models used to study cough causes, mechanisms and possible therapeutic targets stems from multiple sources. First of all, cough induced in the laboratory by mechanical or chemical stimuli is far from natural cough present in human disease. The main objective of this review is to provide a comprehensive summary of animal models currently used in cough research and to address their advantages and disadvantages. We also want to encourage cough researchers to call for precision is research by addressing the sex bias which has existed in basic cough research for decades and discuss the role of specific pathogen-free (SPF) animals., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The role of the cerebellum in controlling the cough motor pattern is not well understood. We hypothesized that cerebellectomy would disinhibit motor drive to respiratory muscles during cough. Cough was induced by mechanical stimulation of the tracheobronchial airways in anesthetized, spontaneously breathing adult cats (8 male, 1 female), and electromyograms (EMGs) were recorded from upper airway, chest wall, and abdominal respiratory muscles. Cough trials were performed before and at two time points after total cerebellectomy (10 minutes and >1 hour). Unlike a prior report in paralyzed, decerebrated, and artificially ventilated animals, we observed that cerebellectomy had no effect on cough frequency. After cerebellectomy, thoracic inspiratory muscle EMG magnitudes increased during cough (diaphragm EMG increased by 14% at 10 minutes, p = 0.04; parasternal by 34% at 10 minutes and by 32% at >1 hour, p = 0.001 and 0.03 respectively). During cough at 10 minutes after cerebellectomy, inspiratory esophageal pressure was increased by 44% (p = 0.004), thyroarytenoid (laryngeal adductor) muscle EMG amplitude increased 13% (p = 0.04), and no change was observed in the posterior cricoarytenoid (laryngeal abductor) EMG. Cough phase durations did not change. Blood pressure and heart rate were reduced after cerebellectomy, and respiratory rate also decreased due to an increase in duration of the expiratory phase of breathing. Changes in cough-related EMG magnitudes of respiratory muscles suggest that the cerebellum exerts inhibitory control of cough motor drive, but not cough number or phase timing in response to mechanical stimuli in this model early after cerebellectomy. However, results varied widely at >1 hour after cerebellectomy, with some animals exhibiting enhancement or suppression of one or more components of the cough motor behavior. These results suggest that, while the cerebellum and behavior-related sensory feedback regulate cough, it may be difficult to predict the nature of the modulation based on total cerebellectomy., Competing Interests: The authors have declared that no competing interests exist.

The study investigates the effects of 6 occlusion conditions on the mechanically induced cough reflex in 15 anesthetized (pentobarbital) spontaneously breathing cats (14♂, 1♀). Esophageal pressure and integrated EMG activities of inspiratory (I) diaphragm and expiratory (E) abdominal muscles were recorded and analyzed. Occlusions: inspiratory (Io), continual I (cIo), during I and active E (I+Eo) cough phase, during I and then E phase with short releasing of airflow before each phase (I-Eo), and E occlusion (Eo) had little influence on cough number. Only continual E occlusion (cEo) reduced the number of coughs by 19 % (to 81 %, p < 0.05). Cough I esophageal pressure reached higher amplitudes under all conditions, but only Eo caused increased I diaphragm motor drive (p < 0.05). Cough E efforts (abdominal motor drive and E amplitudes of esophageal pressure) increased during Eo, decreased during I+Eo (p  < 0.05), and did not change significantly under other conditions (p > 0.05). All I blocks resulted in prolonged I cough characteristics (p < 0.05) mainly cough I phase (incrementing part of the diaphragm activity). Shorter I phase occurred with cEo (p < 0.05). Cough cycle time and active E phase (from the I maximum to the end of cough E motor drive) prolonged (p < 0.05) during all occlusions (E phase duration statistically non-significantly for I+Eo). Airflow block during cough (occlusions) results in secondary changes in the cough response due to markedly altered function of cough central pattern generator and cough motor pattern produced. Cough compensatory effects during airflow resistances are more favorable compared to occlusions. Volume feedback represents significant factor of cough modulation under various pathological obstruction and/or restriction conditions of the respiratory system., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Afferent feedback can appreciably alter the pharyngeal phase of swallow. In order to measure the stability of the swallow motor pattern during several types of alterations in afferent feedback, we assessed swallow during a conventional water challenge in four anesthetized cats, and compared that to swallows induced by fixed (20 Hz) and stochastic (1-20Hz) electrical stimulation applied to the superior laryngeal nerve. The swallow motor patterns were evaluated by electromyographic activity (EMG) of eight muscles, based on their functional significance: laryngeal elevators (mylohyoid, geniohyoid, and thyrohyoid); laryngeal adductor (thyroarytenoid); inferior pharyngeal constrictor (thyropharyngeus); upper esophageal sphincter (cricopharyngeus); and inspiratory activity (parasternal and costal diaphragm). Both the fixed and stochastic electrical stimulation paradigms increased activity of the laryngeal elevators, produced short-term facilitation evidenced by increasing swallow durations over the stimulus period, and conversely inhibited swallow-related diaphragm activity. Both the fixed and stochastic stimulus conditions also increased specific EMG amplitudes, which never occurred with the water challenges. Stochastic stimulation increased swallow excitability, as measured by an increase in the number of swallows produced. Consistent with our previous results, changes in the swallow motor pattern for pairs of muscles were only sometimes correlated with each other. We conclude that alterations in afferent feedback produced particular variations of the swallow motor pattern. We hypothesize that specific SLN feedback might modulate the swallow central pattern generator during aberrant feeding conditions (food/liquid entering the airway), which may protect the airway and serve as potentially important clinical diagnostic indicators., (Copyright © 2020 King, Shen, Musselwhite, Huff, Reed, Poliacek, Howland, Dixon, Morris, Bolser, Iceman and Pitts.)

Anatomical connections are reported between the cerebellum and brainstem nuclei involved in swallow such as the nucleus tractus solitarius, nucleus ambiguus, and Kölliker-fuse nuclei. Despite these connections, a functional role of the cerebellum during swallow has not been elucidated. Therefore, we examined the effects of cerebellectomy on swallow muscle recruitment and swallow-breathing coordination in anesthetized freely breathing cats. Electromyograms were recorded from upper airway, pharyngeal, laryngeal, diaphragm, and chest wall muscles before and after complete cerebellectomy. Removal of the cerebellum reduced the excitability of swallow (i.e., swallow number), and muscle recruitment of the geniohyoid, thyroarytenoid, parasternal (chestwall), and diaphragm muscles, but did not disrupt swallow-breathing coordination. Additionally, diaphragm and parasternal muscle activity during swallow is reduced after cerebellectomy, while no changes were observed during breathing. These findings suggest the cerebellum modulates muscle excitability during recruitment, but not pattern or coordination of swallow with breathing.

The role of pulmonary stretch receptor discharge and volume feedback in modulation of tracheobronchial cough is not fully understood. The current study investigates the effect of expiratory occlusion with or without preceding inspiratory resistance (delivery of tidal or cough volume by the ventilator lasting over the active cough expiratory period) on the cough motor pattern. Experiments on 9 male cats under pentobarbital sodium anesthesia have shown that inspiratory resistance followed by expiratory occlusion increased cough inspiratory and expiratory efforts and prolonged several time intervals (phases) related to muscle activation during cough. Expiratory occlusion (at regular cough volume) decreased number of coughs, increased amplitudes of abdominal electromyographic activity, inspiratory and expiratory esophageal pressure during cough and significantly prolonged cough temporal features. Correlation analysis supported major changes in cough expiratory effort and timing due to the occlusion. Our results support a high importance of volume feedback, including that during cough expulsion, for generation and modulation of cough motor pattern with obstruction or expiratory airway resistances, the conditions present during various pulmonary diseases., (Copyright © 2018. Published by Elsevier B.V.)

Active contraction of the diaphragm and other inspiratory pump muscles during swallow create a negative thoracic pressure to improve the movement of the bolus (food/liquid) into the esophagus. We tested the hypothesis that dorsomedial medullary inspiratory neurons, including the nucleus tractus solitarius (NTS, pre-motor to the phrenic) would be active during swallow induced by oral water infusion. We recorded neurons in the NTS and medial reticular formation in anesthetized spontaneously breathing cats, and induced swallow by injection of water into the oropharynx. Our results indicate that: 1) a majority of inspiratory cells in the dorsomedial medulla are active during swallow, 2) expiratory neurons are present in the medial reticular formation (deeper to the NTS) in unparalyzed cats and a majority of these cells decreased firing frequency during swallow. Our findings suggest that the dorsomedial medulla is a source of inspiratory motor drive during swallow and that a novel population of breathing-modulated neurons that also are modulated during swallowing exist in the medial reticular formation in unparalyzed animals., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0128245.].

The modulation of cough by microinjections of codeine in 3 medullary regions, the solitary tract nucleus rostral to the obex (rNTS), caudal to the obex (cNTS) and the lateral tegmental field (FTL) was studied. Experiments were performed on 27 anesthetized spontaneously breathing cats. Electromyograms (EMG) were recorded from the sternal diaphragm and expiratory muscles (transversus abdominis and/or obliquus externus; ABD). Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Bilateral microinjections of codeine (3.3 or 33mM, 54±16nl per injection) in the cNTS had no effect on cough, while those in the rNTS and in the FTL reduced coughing. Bilateral microinjections into the rNTS (3.3mM codeine, 34±1 nl per injection) reduced the number of cough responses by 24% (P<0.05), amplitudes of diaphragm EMG by 19% (P<0.01), of ABD EMG by 49% (P<0.001) and of expiratory esophageal pressure by 56% (P<0.001). Bilateral microinjections into the FTL (33mM codeine, 33±3 nl per injection) induced reductions in cough expiratory as well as inspiratory EMG amplitudes (ABD by 60% and diaphragm by 34%; P<0.01) and esophageal pressure amplitudes (expiratory by 55% and inspiratory by 26%; P<0.001 and 0.01, respectively). Microinjections of vehicle did not significantly alter coughing. Breathing was not affected by microinjections of codeine. These results suggest that: 1) codeine acts within the rNTS and the FTL to reduce cough in the cat, 2) the neuronal circuits in these target areas have unequal sensitivity to codeine and/or they have differential effects on spatiotemporal control of cough, 3) the cNTS has a limited role in the cough suppression induced by codeine in cats., (Copyright © 2017. Published by Elsevier B.V.)

The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations ( n = 6) or 110 ± 4 nl total in 4 locations ( n = 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing. NEW & NOTEWORTHY The nucleus of the solitary tract contains significant neuronal structures responsible for control of 1 ) cough excitability, 2 ) motor drive during cough, 3 ) cough phase timing, and 4 ) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing., (Copyright © 2017 the American Physiological Society.)

Unilateral cooling of the vagus nerve (<5°C, blocking mainly conductivity of myelinated fibers) and unilateral vagotomy were employed to reduce cough afferent drive in order to evaluate the effects of these interventions on the temporal features of the cough reflex. Twenty pentobarbitone anesthetized, spontaneously breathing cats were used. Cough was induced by mechanical stimulation of the tracheobronchial airways. The number of coughs during vagal cooling was significantly decreased (p<0.001). Inspiratory cough efforts were reduced by approximately 30% (p<0.001) and expiratory motor drive by more than 80% (p<0.001). Temporal analysis showed prolonged inspiratory and expiratory phases, the total cycle duration, its active portion, and the interval between maxima of the diaphragm and the abdominal activity during coughing (p<0.001). There was no significant difference in the average effects on the cough reflex between cooling of the left or the right vagus nerve. Compared to control, vagal cooling produced no significant difference in heart rate and mean arterial blood pressure (p>0.05), however, cold block of vagal conduction reduced respiratory rate (p<0.001). Unilateral vagotomy significantly reduced cough number, cough-related diaphragmatic activity, and relative values of maximum expiratory esophageal pressure (all p<0.05). Our results indicate that reduced cough afferent drive (lower responsiveness) markedly attenuates the motor drive to respiratory pump muscles during coughing and alters cough temporal features. Differences in the effects of unilateral vagal cooling and vagotomy on coughing support an inhibitory role of sensory afferents that are relatively unaffected by cooling of the vagus nerve to 5°C on mechanically induced cough., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered (via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CTI), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered (via the ventilator) during the first half of inspiratory period (at CTI/2-early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CTI, and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CTE1). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CTE1, the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing., (Copyright © 2016. Published by Elsevier B.V.)

We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter and shape afferent input to the respiratory network during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is variable: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for this dynamic feature of a repetitive cough bout. When a single second-order population was split into two subpopulations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing had less variance than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited increased variance in the expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough., (Copyright © 2016 the American Physiological Society.)

Diseases affecting pulmonary mechanics often result in changes to the coordination of swallow and breathing. We hypothesize that during times of increased intrathoracic pressure, swallow suppresses ongoing expiratory drive to ensure bolus transport through the esophagus. To this end, we sought to determine the effects of swallow on abdominal electromyographic (EMG) activity during expiratory threshold loading in anesthetized cats and in awake-healthy adult humans. Expiratory threshold loads were applied to recruit abdominal motor activity during breathing, and swallow was triggered by infusion of water into the mouth. In both anesthetized cats and humans, expiratory cycles which contained swallows had a significant reduction in abdominal EMG activity, and a greater percentage of swallows were produced during inspiration and/or respiratory phase transitions. These results suggest that: a) spinal expiratory motor pathways play an important role in the execution of swallow, and b) a more complex mechanical relationship exists between breathing and swallow than has previously been envisioned.