Publications by authors named "Poliacek Ivan"

34 Publications

Modeling and simulation of vagal afferent input of the cough reflex.

Respir Physiol Neurobiol 2022 07 17;301:103888. Epub 2022 Mar 17.

Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.

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.
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http://dx.doi.org/10.1016/j.resp.2022.103888DOI Listing
July 2022

The role of neuronal excitation and inhibition in the pre-Bötzinger complex on the cough reflex in the cat.

J Neurophysiol 2022 01 8;127(1):267-278. Epub 2021 Dec 8.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.

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 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 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. 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 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.
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http://dx.doi.org/10.1152/jn.00108.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759968PMC
January 2022

Differential effects of acute cerebellectomy on cough in spontaneously breathing cats.

PLoS One 2021 21;16(6):e0253060. Epub 2021 Jun 21.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253060PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216514PMC
November 2021

Distinct modulation of tracheal and laryngopharyngeal cough via superior laryngeal nerve in cat.

Respir Physiol Neurobiol 2021 11 10;293:103716. Epub 2021 Jun 10.

Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic.

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.
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http://dx.doi.org/10.1016/j.resp.2021.103716DOI Listing
November 2021

Animal models of cough.

Respir Physiol Neurobiol 2021 08 26;290:103656. Epub 2021 Mar 26.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Department of Pathophysiology, Martin, Slovakia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.resp.2021.103656DOI Listing
August 2021

Volume feedback during cough in anesthetized cats, effects of occlusions and modulation summary.

Respir Physiol Neurobiol 2021 01 14;283:103547. Epub 2020 Sep 14.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601, Martin, Slovakia.

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.
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http://dx.doi.org/10.1016/j.resp.2020.103547DOI Listing
January 2021

Swallow Motor Pattern Is Modulated by Fixed or Stochastic Alterations in Afferent Feedback.

Front Hum Neurosci 2020 9;14:112. Epub 2020 Apr 9.

Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, KY, United States.

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.
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http://dx.doi.org/10.3389/fnhum.2020.00112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160698PMC
April 2020

The Role of the Cerebellum in Control of Swallow: Evidence of Inspiratory Activity During Swallow.

Lung 2019 04 24;197(2):235-240. Epub 2019 Jan 24.

Department of Neurological Surgery and Kentucky Spinal Cord Injury Research Center, College of Medicine, University of Louisville, Louisville, KY, USA.

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.
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http://dx.doi.org/10.1007/s00408-018-00192-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715301PMC
April 2019

The motor pattern of tracheobronchial cough is affected by inspiratory resistance and expiratory occlusion - The evidence for volume feedback during cough expiration.

Respir Physiol Neurobiol 2019 03 21;261:9-14. Epub 2018 Dec 21.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601, Martin, Slovakia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.resp.2018.12.006DOI Listing
March 2019

Neurons in the dorsomedial medulla contribute to swallow pattern generation: Evidence of inspiratory activity during swallow.

PLoS One 2018 19;13(7):e0199903. Epub 2018 Jul 19.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199903PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053168PMC
December 2018

Cough modulation by upper airway stimuli in cat - potential clinical application?

Open J Mol Integr Physiol 2016 Aug 22;6(3):35-43. Epub 2016 Aug 22.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics.

The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and / or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and / or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.
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http://dx.doi.org/10.4236/ojmip.2016.63004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5606332PMC
August 2016

Role of the dorsomedial medulla in suppression of cough by codeine in cats.

Respir Physiol Neurobiol 2017 12 1;246:59-66. Epub 2017 Aug 1.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 036 01, Martin, Slovakia.

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.
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http://dx.doi.org/10.1016/j.resp.2017.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646267PMC
December 2017

Microinjection of kynurenic acid in the rostral nucleus of the tractus solitarius disrupts spatiotemporal aspects of mechanically induced tracheobronchial cough.

J Neurophysiol 2017 06 1;117(6):2179-2187. Epub 2017 Mar 1.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;

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 ( = 6) or 110 ± 4 nl total in 4 locations ( = 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. The nucleus of the solitary tract contains significant neuronal structures responsible for control of ) cough excitability, ) motor drive during cough, ) cough phase timing, and ) 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.
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http://dx.doi.org/10.1152/jn.00935.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454471PMC
June 2017

Feed-forward and reciprocal inhibition for gain and phase timing control in a computational model of repetitive cough.

J Appl Physiol (1985) 2016 07 9;121(1):268-78. Epub 2016 Jun 9.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida;

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.
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http://dx.doi.org/10.1152/japplphysiol.00790.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967248PMC
July 2016

Changes in vagal afferent drive alter tracheobronchial coughing in anesthetized cats.

Respir Physiol Neurobiol 2016 08 13;230:36-43. Epub 2016 May 13.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601 Martin, Slovakia.

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.
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http://dx.doi.org/10.1016/j.resp.2016.05.008DOI Listing
August 2016

The course of lung inflation alters the central pattern of tracheobronchial cough in cat-The evidence for volume feedback during cough.

Respir Physiol Neurobiol 2016 07 25;229:43-50. Epub 2016 Apr 25.

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Medical Biophysics, Mala Hora 4, 03601 Martin, Slovakia.

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.
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http://dx.doi.org/10.1016/j.resp.2016.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369651PMC
July 2016

Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans.

PLoS One 2015 28;10(5):e0128245. Epub 2015 May 28.

Department of Physiological Sciences, University of Florida, Gainesville, FL, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128245PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447283PMC
April 2016

Effect of laparotomy on the swallow-breathing relationship in the cat.

Lung 2015 Feb 21;193(1):129-33. Epub 2014 Oct 21.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, PO Box 100144, Gainesville, FL, 32610-0144, USA,

Swallow occurs predominantly in the expiratory phase (E) of breathing. This phase preference is thought to contribute to airway protection by limiting the passage of material through the pharyngeal airway with little or no inspiratory (I) airflow. This phase preference is attributed to central interactions between the swallow and breathing pattern generators. We speculated that changes in peripheral mechanical factors would influence the respiratory phase preference for swallow initiation. We induced swallowing in anesthetized spontaneously breathing cats by injection of water into the oropharynx. In animals with intact abdomens, 83 % of swallows were initiated during E, 7 % during I, 7 % during E-I phase transition, and 3 % during I-E transition. In animals with open anterior midline laparotomy, only 38 % of swallows were initiated during E, 33 % during I, 17 % during the E-I transition, and 12 % during I-E. The results support an important role for feedback from somatic and/or visceral thoraco-abdominal mechanoreceptors for swallow-breathing coordination after laparotomy.
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http://dx.doi.org/10.1007/s00408-014-9662-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320662PMC
February 2015

Interactions of mechanically induced coughing and sneezing in cat.

Respir Physiol Neurobiol 2015 Jan 28;205:21-7. Epub 2014 Sep 28.

Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic.

Mutual interactions of cough and sneeze were studied in 12 spontaneously breathing pentobarbitone anesthetized cats. Reflexes were induced by mechanical stimulation of the tracheobronchial and nasal airways, respectively. The amplitude of the styloglossus muscle EMG moving average during the sneeze expulsion was 16-fold higher than that during cough (p<0.01). Larger inspiratory efforts occurred during coughing (p<0.01) vs. those in sneeze. The number of reflexes during simultaneous mechanical stimulation of the nasal and tracheal airways was not altered significantly compared to controls (p>0.05) and there was no modulation in temporal characteristics of the behaviors. When both reflexes occurred during simultaneous stimuli the responses were classified as either sneeze or cough (no hybrid responses occurred). During simultaneous stimulation of both airway sites, peak diaphragm EMG and inspiratory esophageal pressures during sneezes were significantly increased. The expiratory maxima of esophageal pressure and amplitudes of abdominal EMGs were increased in coughs and sneezes during simultaneous mechanical stimulation trials compared to control reflexes.
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http://dx.doi.org/10.1016/j.resp.2014.09.011DOI Listing
January 2015

What is chronic cough in children?

Front Physiol 2014 28;5:322. Epub 2014 Aug 28.

Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France.

The cough reflex is modulated throughout growth and development. Cough-but not expiration reflex-appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.
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http://dx.doi.org/10.3389/fphys.2014.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148026PMC
September 2014

Control of coughing by medullary raphé.

Prog Brain Res 2014 ;212:277-95

Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Institute of Pathophysiology, Martin, Slovakia.

The medullary raphé nuclei participate in the regulation of breathing and airway defensive reflexes. Our focus was to analyze the effects of codeine and kainic acid within the medullary raphé on coughing, sneezing, solitary expulsions, and concomitant breathing changes using models of anesthetized cats (n=12) and rabbits (n=15) and microinjection techniques. Our findings are consistent with (1) involvement of neurons within the medullary raphé in the generation of the cough motor pattern by a codeine-sensitive and -insensitive mechanisms, (2) a contribution of raphé nuclei to the control of expiratory efforts, (3) limited contribution of the medullary raphé to the cough-gating mechanism, (4) minor contribution of respiration/coughing neuronal network, including the portion within raphé nuclei and the respiratory/cough central pattern generator, to the production of the sneeze reflex motor pattern.
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http://dx.doi.org/10.1016/B978-0-444-63488-7.00014-8DOI Listing
April 2015

Variability of the pharyngeal phase of swallow in the cat.

PLoS One 2014 29;9(8):e106121. Epub 2014 Aug 29.

Department of Physiological Sciences, University of Florida, Gainesville, Florida, United States of America.

Objective: The pharyngeal phase of swallow has been thought to be a stereotypical motor behavior.

Study Design: This is a prospective, preclinical, hypothesis driven, one group by three-task design.

Methods: We sought to compare the effects of pharyngeal swabbing, water only, and water plus punctate mechanical stimulation on the spatiotemporal features of the pharyngeal phase of swallow in the cat. Swallow was elicited under these three conditions in six anaesthetized cats. Electromyographic activity was recorded from seven muscles used to evaluate swallow: mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus, and parasternal.

Results: Pharyngeal swabbing in comparison to the other stimulus conditions, results in decreases in post-swallow cricopharyngeus activity (upper esophageal sphincter); a significant increase in parasternal (schluckatmung; swallow breath) activity; and increases in thyrohyoid (laryngeal elevator), thyroarytenoid (laryngeal adductor) and parasternal muscles burst duration. Pearson correlations were found of moderate strength between 19% of burst duration comparisons and weak to moderate relationships between 29% of burst amplitude comparisons. However, there were no positive significant relationships between phase durations and electromyogram amplitudes between any of the muscles studied during swallow.

Conclusions: The results support the concept that a stereotypical behavior, such as pharyngeal swallowing in animal models, can be modified by sensory feedback from pharyngeal mucosal mechanoreceptors. Furthermore, differences in swallow phase durations and amplitudes provide evidence that separate regulatory mechanisms exist which regulate spatial and temporal aspects of the behavior.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106121PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149527PMC
November 2015

Coordination of cough and swallow: a meta-behavioral response to aspiration.

Respir Physiol Neurobiol 2013 Dec 30;189(3):543-51. Epub 2013 Aug 30.

Department of Physiological Sciences, University of Florida, Gainesville, FL, United States. Electronic address:

Airway protections is the prevention and/or removal of material by behaviors such as cough and swallow. We hypothesized these behaviors are coordinated to respond to aspiration. Anesthetized animals were challenged with simulated aspiration that induced both coughing and swallowing. Electromyograms of upper airway and respiratory muscles together with esophageal pressure were recorded to identify and evaluate cough and swallow. During simulated aspiration, both cough and swallow intensity increased and swallow duration decreased consistent with rapid pharyngeal clearance. Phase restriction between cough and swallow was observed; swallow was restricted to the E2 phase of cough. These results support three main conclusions: 1) the cough and swallow pattern generators are tightly coordinated so as to generate a protective meta-behavior; 2) the trachea provides feedback on swallow quality, informing the brainstem about aspiration incidences; and 3) the larynx and upper esophageal sphincter act as two separate valves controlling the direction of positive and negative pressures from the upper airway into the thorax.
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http://dx.doi.org/10.1016/j.resp.2013.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882902PMC
December 2013

Modulation of cough response by sensory inputs from the nose - role of trigeminal TRPA1 versus TRPM8 channels.

Cough 2012 Dec 3;8(1):11. Epub 2012 Dec 3.

Department of Pathophysiology, Comenius University, Jessenius Faculty of Medicine Martin, Sklabinska Str, 26, Martin, 036 01, Slovak Republic.

Unlabelled:

Background: Cough, the most important airways defensive mechanism is modulated by many afferent inputs either from respiratory tussigenic areas, but also by afferent drive from other organs. In animal models, modulation of cough by nasal afferent inputs can either facilitate or inhibit the cough response, depending on the type of trigeminal afferents stimulated.

Methods: In this study we addressed the question of possible bidirectional modulation of cough response in human healthy volunteers by nasal challenges with TRPA1 and TRPM8 agonists respectively. After nasal challenges with isocyanate (AITC), cinnamaldehyde, (-) menthol and (+) menthol (all 10-3 M) nasal symptom score, cough threshold (C2), urge to cough (Cu) and cumulative cough response were measured).

Results: Nasal challenges with TRPA1 relevant agonists induced considerable nasal symptoms, significantly enhanced urge to cough (p<0.05) but no statistically significant modulation of the C2 and cumulative cough response. In contrast, both TRPM8 agonists administered to the nose significantly modulated all parameters including C2 (p<0.05), Cu (p<0.01) and cumulative cough response (p <0.01) documenting strong anti irritating potential of menthol isomers.

Conclusions: In addition to trigeminal afferents expressing TRP channels, olfactory nerve endings, trigemino - olfactoric relationships, the smell perception process and other supramedullar influences should be considered as potential modulators of the cough response in humans.
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http://dx.doi.org/10.1186/1745-9974-8-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546011PMC
December 2012

Contribution of medullary raphé to control of coughing--codeine trials in cat.

Respir Physiol Neurobiol 2012 Oct 18;184(1):106-12. Epub 2012 Aug 18.

Department of Medical Biophysics, Jessenius Faculty of Medicine, Comenius University, Mala Hora 4, 03601 Martin, Slovakia.

In order to determine if a codeine-sensitive control system for cough exists in the medullary raphé four microinjections of codeine (3.3 and 16.5 mM; 36.6±0.7 nl 1.5 and 3 mm rostral to the obex at the depths 1.5 and 3 mm; the total dose 1.12±0.3 nmol, 9 animals) were performed on pentobarbitone anesthetized spontaneously breathing cats. Amplitudes of abdominal muscle EMG moving averages during mechanically induced tracheobronchial cough decreased by 18% compared to control coughs (p<0.05). The duration between maxima of cough diaphragm and abdominal muscle EMG discharge, cough expiratory phase duration and period of relative motor quiescence between coughs were increased (all p<0.05). Cough number, other cough parameters, and cardiorespiratory characteristics were not altered significantly. Control microinjections of artificial cerebro-spinal fluid had no effect on coughing. Codeine sensitive neurons involved in the generation or modulation of motor pattern of tracheobronchial cough are located in the medullary midline raphé nuclei; however, their contribution to codeine induced cough suppression is limited.
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http://dx.doi.org/10.1016/j.resp.2012.08.010DOI Listing
October 2012

Co-ordination of cough and swallow in vivo and in silico.

Exp Physiol 2012 Apr 23;97(4):469-73. Epub 2011 Dec 23.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.

Coughing and swallowing are airway-protective behaviours. The pharyngeal phase of swallowing prevents aspiration of oral material (saliva, food and liquid) by epiglottal movement, laryngeal adduction and clearing of the mouth and pharynx. Coughing is an aspiration-response behaviour that removes material from the airway. Co-ordination of these behaviours is vital to protect the airway from further aspiration-promoting events, such as a swallowing during the inspiratory phase of coughing. The operational characteristics, primary strategies and peripheral inputs that co-ordinate coughing and swallowing are unknown. This lack of knowledge impedes understanding and treatment of deficits in airway protection, such as the co-occurrence of dystussia and dysphagia common in Parkinson's and Alzheimer's diseases, as well as stroke.
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http://dx.doi.org/10.1113/expphysiol.2011.063362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345517PMC
April 2012

Blood pressure changes alter tracheobronchial cough: computational model of the respiratory-cough network and in vivo experiments in anesthetized cats.

J Appl Physiol (1985) 2011 Sep 30;111(3):861-73. Epub 2011 Jun 30.

Dept. of Physiological Sciences, College of Veterinary Medicine, Univ. of Florida, Gainesville, FL 32610, USA.

We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input.
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http://dx.doi.org/10.1152/japplphysiol.00458.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174787PMC
September 2011

Microinjection of codeine into the region of the caudal ventral respiratory column suppresses cough in anesthetized cats.

J Appl Physiol (1985) 2010 Apr 21;108(4):858-65. Epub 2010 Jan 21.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20-32 nl) in the cVRC reduced cough number by 29% (P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% (P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% (P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30-40 nl) on ABD activity induced by a microinjection of D,L-homocysteic acid (30 mM, 27-40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC D,L-homocysteic acid microinjection (30 mM, 28-32 nl) by 47% (P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid.
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http://dx.doi.org/10.1152/japplphysiol.00783.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853207PMC
April 2010

Short reflex expirations (expiration reflexes) induced by mechanical stimulation of the trachea in anesthetized cats.

Cough 2008 Apr 28;4. Epub 2008 Apr 28.

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, PO box 100144, 1600 SW Archer Road, Gainesville, Florida, 32610-0144, USA.

Fifty spontaneously breathing pentobarbital-anesthetized cats were used to determine the incidence rate and parameters of short reflex expirations induced by mechanical stimulation of the tracheal mucosa (ERt). The mechanical stimuli evoked coughs; in addition, 67.6% of the stimulation trials began with ERt. The expiration reflex mechanically induced from the glottis (ERg) was also analyzed (99.5% incidence, p < 0.001 compared to the incidence of ERt). We found that the amplitudes of abdominal, laryngeal abductor posterior cricoarytenoid, and laryngeal adductor thyroarytenoid electromyograms (EMG) were significantly enhanced in ERg relative to ERt. Peak intrathoracic pressure (esophageal or intra-pleural pressure) was higher during ERg than ERt. The interval between the peak in EMG activity of the posterior cricoarytenoid muscle and that of the EMG of abdominal muscles was lower in ERt compared to ERg. The duration of thyroarytenoid EMG activity associated with ERt was shorter than that in ERg. All other temporal features of the pattern of abdominal, posterior cricoarytenoid, and thyroarytenoid muscles EMGs were equivalent in ERt and ERg.In an additional 8 cats, the effect of codeine administered via the vertebral artery was tested. Codeine, in a dose (0.03 mg/kg) that markedly suppressed cough did not significantly alter either the incidence rate or magnitudes of ERt.In the anesthetized cat the ERt induced by mechanical stimulation of the trachea was similar to the ERg from the glottis. These two reflex responses differ substantially only in the frequency of occurrence in response to mechanical stimulus and in the intensity of motor output.
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http://dx.doi.org/10.1186/1745-9974-4-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2405785PMC
April 2008
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