Publications by authors named "Kotmanova Zuzana"

10 Publications

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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

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

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

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

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

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
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