Differential effects of kainic acid lesions in medullary raphe on cough and sneeze in anesthetized rabbits.

The effects of microinjections of the excitatory neurotoxin kainic acid (2 mg/ml; 49 ± 1 nl) on the mechanically induced tracheobronchial cough, sneeze, and solitary expulsions from the trachea were examined in 11 anesthetized rabbits. Kainic acid was injected into the medulla (1.6-2.8 mm rostral to the obex, 1.4-1.6 and 2.9-3.2 mm below the dorsal medullary surface). Blood pressure, esophageal pressure (EP), and electromyograms (EMGs) of the diaphragm (DIA) and abdominal muscles (ABD) were recorded. Kainic acid reduced the number of coughs (means ± SE) from 3.8 ± 2.0 to 0.9 ± 0.7 (p = 0.016), the amplitude of DIA cough from 90 ± 11 to 42 ± 13 % (p = 0.004), ABD EMG moving average from 103 ± 9 to 37 ± 15 % (p = 0.006), and inspiratory from 0.67 ± 0.13 to 0.36 ± 0.12 kPa (p = 0.013) and expiratory EP from 1.70 ± 0.54 to 0.89 ± 0.46 kPa (p = 0.008). Kainic acid had no effect on the number of sneeze reflexes nor did it affect solitary expulsions from the trachea. These effects were accompanied by significant increases in systemic blood pressure and respiratory rate. Spatiotemporal analysis of the cough and sneeze reflexes revealed increases in the duration of cough active expiratory phase, in the intervals between maxima of DIA and ABD EMG discharges, and in the active portion of total cough phase duration. Our findings suggest a diverse role of raphe neurons in the central control of motor airway responses such as coughing and sneezing. A complex function of raphe neurons in the generation of the cough motor pattern also is suggested.

Provocation of aspiration reflexes and their effects on the pattern of cough and reflex apnea in cats.

Aspiration reflexes (AspRs) manifesting as reflex spasmodic inspirations and their effects on motor pattern of tracheobronchial cough and reflex apnea were studied on 22 spontaneously breathing pentobarbitone-anesthetized cats. AspRs induced during cough inspiration enhanced peak inspiratory (P<0.01) and expiratory (P<0.02) esophageal pressures, amplitudes of diaphragm (P<0.01) and abdominal muscles (P<0.05) EMG activity, and prolonged the entire expiratory period (P<0.01) and total cycle duration (P<0.05) of cough. Transient inhibitions and splits of cough expiration frequently occurred with AspR within active cough expiratory period; however, cough spatiotemporal characteristics were not altered significantly. Sub-threshold nasopharyngeal stimulation failing to provoke AspR had no significant effects on coughing. Hering-Breuer inflation apnea was moderately prolonged by AspRs (20%; P<0.05), unlike the apnea produced by continual mechanical laryngeal stimulation. AspRs are inducible during tested behaviors interacting with their motor pattern. Central mechanisms involving pulmonary stretch receptor stimulation is suggested for modulation of cough and inflation apnea by AspR.

Excitability and rhythmicity of tracheobronchial cough is altered by aspiration reflex in cats.

Effects of nasopharyngeal stimulation on excitability and rhythmicity of mechanically induced tracheobronchial cough were examined on 18 pentobarbitone anesthetized cats. After the 17.2+/-2.4 aspiration reflexes (AspRs), tracheobronchial stimulation evoked lower number of coughs (P<0.05) with longer latency to the diaphragm activation (P<0.02), compared to control. AspRs induced within "inter-cough" periods (motor quiescence between individual coughs; 3.3 AspRs per period) reduced cough number by 50% (P<0.01), shortened cough-related abdominal activity (P<0.02), prolonged inter-cough period (P<0.02), and the total cough cycle duration (P<0.05). Cough efforts occurred irregularly with very variable "inter-cough" distances and total cough cycle durations. The subthreshold nasopharyngeal stimulation (failing to evoke AspR) did not affect rhythmic coughing. AspRs induced during persisting post-stimulation coughs did not significantly reduce their number. Excitability and rhythmicity of mechanically induced tracheobronchial cough can be reduced by AspRs, but not by subthreshold nasopharyngeal stimulation. The suppressive effect of spasmodic inspirations on chronic cough is suggested.

Medullary raphe midline is involved in production of expulsive expirations in anesthetized rabbits.

Effects of kainic acid lesions in the medullary raphe midline on reflex expirations induced mechanically from the trachea were examined. Spontaneously breathing rabbits were anesthetized by ketamine and xylazine i.m., followed by pentobarbitone i.v. Excitatory neurotoxin kainic acid (2 mg/ml in artificial CSF, total volume of 55-100 nl) was pressure microinjected into the medullary midline, rostral to the obex (2 microinjections at 2 different depths). The lesion (mostly affected the obscurus and magnus raphe nuclei) reduced the number of reflex expirations by 80% and expiratory amplitudes of esophageal pressure, abdominal EMG moving averages, and abdominal EMG powers by 71%, 62%, and 57%, respectively (in all cases P<0.05). The duration of abdominal activity in post-lesion responses was not altered. Control microinjections of artificial CSF had no effect on the reflex responses. We conclude that in rabbits, the medullary raphe nuclei participate in the control of expiratory expulsions originating from the trachea.

Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats.

Experiments were carried out to determine whether there are separate drives from the selected neuronal networks of the brainstem affecting the discharge patterns of laryngeal and respiratory pump muscles during cough. Twenty-four non-decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone were used. Microinjections of kainic acid into the lateral tegmental field of the medulla, medullary midline or pontine respiratory group eliminated the cough evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no effect on them). No pattern of laryngeal muscle activities following lesions resembled the laryngeal cough response. Lesions of the target regions did not result in any apparent changes in the eupnoeic pattern of laryngeal activity. Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine respiratory group seem to be indispensable for the configuration of the central cough motor pattern. However, these neurons do not appear to be essential for the discharge patterns of laryngeal motoneurons during eupnoea. The residual laryngeal "cough" responses are probably mediated by an additional motor drive.

Cough, expiration and aspiration reflexes following kainic acid lesions to the pontine respiratory group in anesthetized cats.

The importance of neurons in the pontine respiratory group for the generation of cough, expiration, and aspiration reflexes was studied on non-decerebrate spontaneously breathing cats under pentobarbitone anesthesia. The dysfunction of neurons in the pontine respiratory group produced by bilateral microinjection of kainic acid (neurotoxin) regularly abolished the cough reflexes evoked by mechanical stimulation of both the tracheobronchial and the laryngopharyngeal mucous membranes and the expiration reflex mechanically induced from the glottis. The aspiration reflex elicited by similar stimulation of the nasopharyngeal region persisted in 73% of tests, however, with a reduced intensity compared to the pre-lesion conditions. The pontine respiratory group seems to be an important source of the facilitatory inputs to the brainstem circuitries that mediate cough, expiration, and aspiration reflexes. Our results indicate the significant role of pons in the multilevel organization of brainstem networks in central integration of the aforementioned reflexes.

Activity of the laryngeal abductor and adductor muscles during cough, expiration and aspiration reflexes in cats.

We studied the temporal relationships and the patterns of electromyographic activities of the posterior cricoarytenoid and thyreoarytenoid muscles (laryngeal abductor and adductor), the diaphragm and abdominal muscles in anesthetized cats during mechanically induced tracheobronchial and laryngopharyngeal coughs, expiration and aspiration reflexes. The posterior cricoarytenoid muscle activity reached the maxima just before the peak of diaphragmatic activity in both types of cough and aspiration reflexes and slightly before the top of abdominal muscle activity in coughs and the expiration reflex. Thus, this muscle contributes to the inspiratory phase of coughs and aspiration reflex and also to the expulsive phase of coughs and the expiration reflex. The thyreoarytenoid muscle presented strong discharges in the compressive phase of coughs and expiration reflex (during the rising part of the abdominal muscle activity) and in the subsequent laryngoconstriction (following the diaphragmal and/or abdominal muscle activity) in all four reflexes. This muscle was also slightly activated at the beginning of the aspiration reflex. The existence of four phases of the cough reflex is also discussed.

Kainic acid lesions to the lateral tegmental field of medulla: effects on cough, expiration and aspiration reflexes in anesthetized cats.

We have tested the hypothesis that neurons of both the ventral reticular nucleus and the adjacent parts of the lateral tegmental field (LTF) may be important for the production of motor programs associated with cough, expiration and aspiration reflexes. Our studies were conducted on non-decerebrate, spontaneously breathing cats under pentobarbitone anesthesia. Dysfunction of the medullary LTF region above the obex, produced by uni- or bilateral injections of kainic acid (a neurotoxin), regularly abolished the cough reflex evoked by mechanical stimulation of both the tracheobronchial and laryngeal regions and in most cases also the expiration reflex induced from the glottal area. However, some electrical activity still occurred in the neurogram of the recurrent laryngeal nerve during probing the laryngeal and glottal regions. Interestingly, the aspiration reflex elicited from the nasopharynx regularly persisted, although with lower intensity after the LTF lesion. Nevertheless, successive midcollicular decerebration performed in four cats also abolished the aspiration reflex. These experiments demonstrate the importance of medullary LTF neurons for the normal occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is that the blockade of the LTF neurons may remove an important source of a facilitatory input to the brainstem circuitries that mediate cough and expiration reflexes. In addition, the potential importance of the mesencephalic reticular formation for the occurrence of the aspiration reflex and the role of the LTF in modulating both the eupnoeic breathing and the blood pressure are also discussed.

Effects of medullary midline lesions on cough and other airway reflexes in anaesthetized cats.

The involvement of rapheal and medial parts of the medullary reticular formation in both generation of airway reflexes and changes in breathing were studied in 18 chloralose or pentobarbitone anaesthetized, non-paralyzed cats. Chemical lesions to the medullary midline region (0-4 mm rostral to the obex) produced by localized injections of the neurotoxin kainic acid regularly abolished the cough reflexes evoked from the tracheobronchial and laryngopharyngeal regions and in most cases also the expiration reflex induced from the glottal area. The aspiration reflex elicited from the nasopharynx was spared, but was less intense. However, the signs of cough and expiration reflexes were preserved in the neurogram of the recurrent laryngeal nerve. The experiments have shown the importance of raphe nuclei and other medullary midline structures for the occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is the removal of an important source of facilitatory input to the spinal respiratory motoneurons or to the brainstem circuitries that mediate cough and expiration reflexes. The role of the medullary midline in modulation of eupnoeic breathing and blood pressure is also discussed.

Laryngeal patency and expiration reflex following focal cold block of the medulla in the cat.

The involvement of the intermediate area and Bötzinger complex (BOT) of the rostral ventral respiratory group (r-VRG) in laryngeal control and generation of the expiration reflex were studied in anaesthetized non-paralyzed cats Focal cooling (to 20 degrees C) of the nucleus paraambigualis (NPA) caused changes in the frequency and timing of breathing with the concomitant rise in laryngeal resistance. Cooling of the nucleus ambiguus resulted in a consistent drop in laryngeal resistance. Alterations in timing and intensity of breathing but no changes in laryngeal patency were found during cooling of the BOT. The expiration reflex was inhibited by cooling of either the NPA or BOT. The role of these medullary regions in the control of laryngeal patency and central integration of the expiration reflex is discussed.

[Planimetric characteristics of the optic papilla in relation to age]. / Planimetrické charakteristiky papily optiku vo vzt'ahu k veku.

Percentage relation of the neuroretinal rim area to the total optic disc area was examined planimetrically in relation to the age of 116 probands having no optic disease and divided into the age decades from 3 to 7. In 3rd decade percentage of the neuroretinal rim area was on average 90.26% (min. 81.2; max. 93.6 standard deviation 3,225). In 4th decade average area was 89.92% (min. 83.7; max. 96.5 standard deviation 3,494). In 5th decade average area of the neuroretinal rim area was 88.583% (min. 78.6; max. 95.5 standard deviation 4,496). In 7th decade average are was 82.448% (min. 73.8; max. 93.5 standard deviation 4,758). Significance of the value differences found by means of t-Student non-pair test: significant differences were found between the parametres in 3rd and 6th decades (p is less than 0.01); between 3rd and 7th decades (p is less than 0.001); between 4th and 6th decades (p is less than 0.01); between 4th and 7th decades (p is less than 0.001); between 5th and 7th age decades (p is less than 0.001) and between 6th and 7th age decades (p is less than 0.01). No significant differences were found between the parametres of the age decades 3 and 5, 3 and 4, 4 and 5, 6 and 7.

Characteristics of augmented breaths provoked by almitrine bismesylate in cats.

The contribution of almitrine bismesylate to the occurrence and pattern of augmented breaths was studied in fifteen spontaneously breathing, anaesthetized cats. Breathing was via a tracheostomy, while the laryngeal resistance to airflow was measured with the larynx isolated in situ. Almitrine bismesylate at a dose of 0.5 mg kg-1 of body weight was injected intravenously in the intact animals and following bilateral vagotomy which spared the right recurrent laryngeal nerve. Almitrine injected intravenously elicited augmented breaths within the first 45 s in thirteen cats and within 1 min in the remaining two cats. During augmented breaths inspiratory and expiratory airflows rose, the mean increases being 385.2 and 159.6% respectively above the controls (P less than 0.01). The inspiratory laryngeal resistance declined to 77.7% of the control (P less than 0.01) and expiratory laryngeal resistance increased by 95.4% above the control level (P less than 0.01). The inspiratory and expiratory times were prolonged by 56 and 58% compared with baseline breathing. Following the augmented breaths the respiratory airflows exceeded baseline values, the respiratory timing was slightly reduced, and the inspiratory laryngeal resistance was significantly lowered below the control level (P less than 0.01). The expiratory laryngeal resistance showed the same trend without statistical significance. Bilateral vagotomy abolished the occurrence of augmented breaths following almitrine injection.

Effects of focal cooling of medulla oblongata structures on quiet breathing in cats.

Experiments were carried out on 16 anaesthetized, non-paralysed cats to determine the effects of unilateral, successive focal cooling of the nuclei of the dorsal and ventral respiratory groups (DRG, VRG) of the medulla oblongata on quiet breathing parameters. The results of cold block tests of the respiratory nuclei showed that: 1. Compared with the control state, cooling of the ventrolateral part of the nucleus solitarii (vl. NTS) and the rostral part of the nucleus retroambigualis (r. NRA) to 20 degrees C or 15 degrees C decreased the respiration rate (p less than 0.001), prolonged the inspiration time (p less than 0.01 and p less than 0.001 respectively) and the development of apneustic breathing. A decrease in the inspiratory pleural pressure values (p less than 0.01) was found after cooling the r. NRA region to 15 degrees C. In 45% of the cases of cooling of the vl. NTS and 66.7% of cooling of the r. NRA to 15 degrees C, an incidence of short inspiratory efforts was observed. 2. Focal cooling of the nucleus retrofacialis (nucl. RF) region to 20 degrees C always arrested rhythmic respiration. 3. The effects of unilateral focal cooling of the respiratory nuclei were always bilaterally symmetrical and, after discontinuing cooling, reversible. 4. The findings indicate that the inspiratory neurones of the r. NRA participate more in regulation of the intensity of inspiration than those of the vl. NTS, while the nucl. RF region may be a part of central regulatory mechanisms essential for the maintenance of rhythmic breathing in cats.

Spectral analysis of respiratory parameters in defensive respiratory reflexes.

A detailed analysis of respiratory signals in normal breathing and defensive respiratory reflexes was performed to obtain maximum information that can be used for modelling of respiratory processes. Physiological interpretation of the problem is difficult and requires further measurements to achieve convincing conclusions. We suggest therefore that the search for appropriate methodological backgrounds should contribute to further clarification of the problems concerned with reciprocal linkage of the respiratory signals. Appropriate attention must be paid to investigations aimed at explaining the regulatory mechanisms of breathing.