Cough and swallow after laparotomy in anesthetized cats.

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.

Differential inhibition of cough by GABAA and GABAB receptor antagonists in the nucleus of the solitary tract in cats.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Interactions of mechanically induced coughing and sneezing in cat.

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.

Control of coughing by medullary raphé.

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.

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

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.

Central antitussive effect of codeine in the anesthetized rabbit.

BACKGROUND: Codeine represents a commonly used drug to suppress cough. Central antitussive effect of codeine has been confirmed in a number of animal studies. However, available data related to antitussive activity of codeine in rabbits are very limited. OBJECTIVE: We investigated the effects of codeine on cough, single expiratory responses (expiration-like reflex) induced by mechanical tracheo-bronchial stimulation, and on the sneeze reflex in the anesthetized rabbit. MATERIAL AND METHODS: Twenty pentobarbitone anesthetized spontaneously breathing rabbits were used for the study. Increasing doses of codeine (codeinum dihydrogenphosphate, Interpharm) were injected intravenously (iv); 0, 0.15, 0.76, and 3.78 mg/kg of codeine dissolved in saline, 0.25 ml/kg) or intracerebroventricularly (icv); 0, 0.015, 0.076, and 0.378 mg/kg of codeine dissolved in artificial cerebrospinal fluid, 0.033 ml/kg. RESULTS: Both iv and icv injections of codeine led to a dose-dependent reduction of coughing provoked by tracheo-bronchial stimulation; however, the doses differed substantially. The effective cumulative dose for a 50% reduction in the number of coughs was 3.9 and 0.11 mg/kg after iv and icv administration of codeine, respectively; representing about 35-fold higher efficacy of the icv route. The numbers of expiration-like responses and sneeze reflex responses remained unchanged. CONCLUSIONS: The study confirmed the central antitussive effect of codeine, but showed a low sensitivity of sneeze and expiration reflex to codeine. We validated the experimental model of an anesthetized rabbit for studies on central antitussive action.

Placenta and umbilical cord blood deserve attention.

OBJECTIVES: This work follows up with our already published results concerning consequences of lead on prenatal and postnatal development of child in connection with the rise of hyperkinetic syndrome (ADHD). This disease has in children increasing tendency all over the world. METHODS: In our work we used a set of histological and histochemical methods, method of scanning electron microscopy, infrared spectroscopy and statistical evaluation. RESULTS: Our new method for proof of lead in placenta enabled us to show how lead is cumulated in syncytiotrophoblast. We have found release of lead from mother's erythrocytes in the intervillous space and receipt of lead by erythrocytes of fetus in the vessels of the villi of placenta. This finding enriches knowledge about relation between mother's erythrocytes, lead, calcium that is lead carrier, syncytiotrophoblast, and erythrocytes of fetus in the vessels of placental villi. We have proved that syncytiotrophoblast is the most frequent place for cumulation of lead deposits. We verified our ecomorphologic results by means of infrared spectroscopy in cooperation with physicists and statistically evaluated occurrence of ADHD in particular age categories what helps to fill gaps in knowledge of ADHD etiology. CONCLUSIONS: Our finding of lead in umbilical cord blood immediately after the child birth is forewarning against the possible rise of the ADHD. This finding facilitates early diagnostics and means preventing step against the rise, development and consequences of this disease. The obtained results give evidence about the serious influence of mother's dwelling in environment polluted with neurotoxic metal - lead on the prenatal and postnatal development of child.