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Biomedical subjects

W A Karczewski

Publications and source records attributed to W A Karczewski.

At least 19 recordsLinked to original sources

Horseradish peroxidase localization of the mylohyoid motoneurones in the rabbit.

Experiments were performed with anaesthetized (urethan and chloralose) spontaneously breathing rabbits. Horseradish peroxidase (HRP) was injected (1 mg) with a Hamilton syringe into the end of the sectioned mylohyoid nerve. The HRP-labelled neurones could be localized in the motor nucleus of the trigeminal nerve (N.V.mt.). It was found that the labelled neurones are present in the caudal and intermediate part of the nucleus. However, their largest agglomerations were noted in the caudal part, where they occupied the entire frontal section of the nucleus. It is assumed that the N.V.mt. directing their axons to the muscles of the upper respiratory airways, simultaneously send collaterals to the central respiratory neurones participating in the regulation of the respiratory rhythm. According to this hypothesis the neurones of the N.V.mt. may ensure synchronisation between the upper and lower respiratory system.

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The respiratory response to magnetic stimulation of the cortex in the unanaesthetized baboon.

Transcranial magnetic stimulation has been used to study cortical input to the respiratory system in unanaesthetized baboons. Single magnetic pulse caused usually a short-latency excitation with subsequent inhibition in stimulated inspiratory phase and change in the amplitude and timing of the respiratory cycle. The results suggest that cortical information is processed by the medullary pattern generator.

Animals↗

The role of neural connections crossed at the cervical level in determining rhythm and amplitude of respiration in cats and rabbits.

The part played by crossed cervical pathways in determining respiratory rhythm and phrenic nerve amplitude was studied in rabbits and cats. The animals were anesthetized with halothane, paralyzed, vagotomized and mechanically ventilated. All decussating brain stem pathways were surgically interrupted. This resulted in asynchronous firing of the respiratory nerves on the left and right side of the body. However, both frequency and amplitude of the respiratory output depended on the mutual phase relationships due to neural connections crossed at the cervical level. Analysis of the mutual phase and amplitude relationships lead to the following conclusions. a. Phrenic motor neurons receive during inspiration a considerable amount of excitation via diffused pathways crossing the midline at C4-C6 level. b. Phrenic motor neurons are actively inhibited via crossed cervical pathways. c. The level of tonic bias transmitted via descending bulbo-spinal pathways significantly influences the magnitude of PhN output. d. Activity of phrenic motor neurons is transmitted back to the bulbar respiratory centers via an ascending spino-bulbar pathway.

Animals↗

Motor nucleus of the V-th nerve and the control of breathing (Breuer-Hering reflexes and apneustic breathing).

Earlier studies from this department have demonstrated that neurones of the V-th nerve motor nucleus (NVmt) have oligosynaptic, inhibitory output to the inspiratory motoneurone pool being themselves under the influence of a polisynaptic input from vagal afferents. To check the hypothesis that NVmt is a part of the pneumotaxic mechanism, we studied the effects of pharmacological mictroblockade of the NVmt on Breuer-Hering reflexes in halothane-anaesthetized, paralyzed and artificially ventilated rabbits. Activities of NVmt neurones and phrenic nerve firing were recorded. Acid-base balance was controlled and histologic examinations were routinely performed. Expiratory activities were regularly found in NVmt. Its blockade elicited a typical apneustic breathing. During the blockade the Breuer-Hering reflexes gave "paradoxical" effects: an increase in central respiratory frequency following inflation, inspiratory apneusis in response to deflation. We conclude that the NVmt is an important component of the pneumotaxic mechanism or even the anatomical substrate of the pneumotaxic "centre".

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Breuer-Hering reflexes in ketamine-induced apneustic breathing in the rabbit.

The effects of ketamine on the activities of the mylohyoid nerve (a branch of the Vth nerve) and of both phrenic nerves were investigated in rabbits anaesthetized with halothane, paralyzed and artificially ventilated. Intravenous administration of ketamine elicited a marked prolongation of the phrenic inspiratory discharge (without significantly affecting its amplitude) and a depression of the mylohyoid expiratory activity. An elimination of the volume-related input from the lungs ("no-inflation manoeuvre") or deflation elicited under these conditions typical apneustic pattern of breathing. The response to tracheal occlusion at peak-inspiration was "classical". We conclude that ketamine inhibits the Vth nerve motor nucleus which is not only an important component of the central inspiratory-inhibitory neurones but also a "relay station" between the vagal and the central inspiratory "off-switch" mechanisms.

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Augmented breath provoked by lung inflation in cat.

The rate of occurrence and magnitude of provoked augmented breath (PAB) were studied as the function of lung expansion applied at different intervals (15-180 s). Together with phrenic nerve activity (Phr.) the activities of recurrent laryngeal (RL) and hypoglossal (Hyp) nerves were investigated during PAB. The experiments were carried out in 10 cats anesthetised, paralysed and artificially ventilated by means of a phrenic nerve-driven respiratory. Lung expansion was performed by increasing the gain of the servorespirator for one breath. PAB could be elicited when the interval between subsequent inflations was longer than 30 s ("refractory time"). We did not find out any consistent relationship, common for all experiments, between the value of the interval (greater than 30 s) and the rate of occurrence of PAB as well as between the volume of lung inflation and the magnitude of PAB. During PAB registered on Phr., activities of RL and Hyp were usually inhibited. It is concluded that PAB depends upon the instantaneous balance of excitatory and inhibitory vagal influences centrally differentiated at various respiratory outputs. Its amplitude and occurrences are therefore difficult to predict. Thus, PAB can be hardly compared with spontaneous deep breath.

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Respiratory effects of pontine, medullary and spinal cord midline sections in the rabbit.

Experiments were performed on halothane anaesthetized, paralyzed rabbits with vagi intact or cut. In vagotomized rabbits separation of both halves of the medulla by a midline section resulted in a 'desynchronization' of both phrenic and both efferent vagal inspiratory volleys. Activities of all these nerves fall and respiratory frequency decreased. In animals with intact vagi the inspiratory volleys generated by each half of the brainstem were locked to the respirator (and consequently to each other). Elimination of the phasic feedback by stopping the respirator led to 'desynchronization'. Extension of the incision through the pons and midbrain increased phrenic amplitude almost to control values. During 'desynchronized' firing the coincident volleys exhibited markedly bigger amplitude than those which appeared in the opposite phase, i.e. during the silent period of the other phrenic. Hemisection at C1 level or a cervical spinal cord midline myelotomy eliminated the amplitude differences between coinciding and non-coinciding volleys. Amplitude of efferent vagal activity was always constant and synchronous with the ipsilateral phrenic. Our findings indicate the existence of bulbo-spinal excitatory and inhibitory pathways which affect phrenic motoneurones from the opposite side. We conclude that integration at pontine and cervical spinal cord level may significantly influence the respiratory output.

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The split-respiratory centre in the cat: responses to hypercapnia.

In 22 cats anaesthetized with halothane, vagotomised, paralyzed with d-tubocurarine and artificially ventilated, the medulla was split in the midline and the response of phrenic motoneurones, efferent vagus nerve and medullary respiratory neurones to hypercapnia was studied. In 18 successful experiments the mid-sagittal incision abolished all electrical activities but an inhalation of a 5% CO2-oxygen mixture promptly restored rhythmic firing in both the medullary units and efferent nerves when PaCO2 reached 55 mm Hg on the average (mean pH = 7.20). Switching the ventilation back to normocapnia was followed by a gradual disappearance of the activities usually when PaCO2 and pH returned to control values. We conclude that splitting the brainstem in cat affects the respiratory rhythmogenesis, presumably by increasing the CO2-threshold of medullary respiratory neurones.

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Phrenic motoneurone activity in split-brainstem cats and monkeys.

A mid-line incision of the lower brainstem (from 2 mm caudal to 14 mm rostral to the obex) was performed in 14 cats and (from 2 mm caudal to 7 mm rostral to the obex) in three green monkeys and its effects on the respiratory activity of both phrenic nerves were studied under similar experimental conditions (halothane anaesthesia, artificial ventilation). Splitting the medulla in cats abolished the phrenic nerve activity under eupnoeic conditions, but hypercapnia or (with more rostral cuts) hypercapnia with hypoxia restored synchronous, rhythmic firing in both phrenic nerves. The response to splitting in eupnoeic monkeys was qualitatively different and consisted in a 'desynchronisation', i.e. independent firing of both phrenic nerves at different rhythms and patterns. It is concluded that cats and monkeys have basically different functional organisation of the respiratory controller.

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The effects of brainstem transection on respiratory activity in the rabbit.

Mid-sagittal incisions and transverse hemisections of the medulla were performed in rabbits anaesthetized with halothane and artificially ventilated at eupnoeic level. A midsagittal incision extending from the obex to (at least) 4 mm rostral elicited asynchronous (independent) firing in both phrenic nerves. A subsequent transverse hemisection interrupted the activity of the ipsilateral phrenic nerve. An electrical stimulation of the vagal input temporarily restored this activity. A midsagittal incision, which had not completely separate both halves of the medulla, did not affect the synchrony of firing of both phrenic nerves; in these cases also the transverse hemisection did not arrest the phrenic nerve activity. It is concluded that synchronous activity of the inspiratory output depends upon intact connnections crossing in the lower medulla and that proper generation of respiratory pattern depends upon a critical level of excitation created by neurones at rostral pontine and suprapontine levels of the CNS, neighboring structures (presumably including the medial reticular formation) and/or vagal input. A concept of a "critical mass" of active neurones is introduced.

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Respiratory activity generated by a split brainstem preparation of the rabbit.

Mid-sagittal incisions of the brainstem were performed in anaesthetized, vagotomised, paralysed and artificially ventilated rabbits. The activity of both phrenic nerves, blood pressure and end-tidal CO2 percent were continuously monitored. The results fell into two groups: in one of them a relatively small separation of both halves of the medulla extending from the obex to at least 4 mm rostrally elicited asynchronous firing in both phrenic nerves ("split respiratory centre"). In the other group, in which the incisions were placed either more caudally or more rostrally, or when small strands of the nervous tissue were left to provide connections between both sides of the brainstem, this. phenomenon did not appear. It is concluded that there are two symmetrical respiratory networks in both halves of. the brainstem and that their synchronous firing depends upon intact connections extending from the obex to the caudal end of nucleus of VII nerve.

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The role of timing and magnitude of the vagal input in controlling the phrenic output in rabbits and baboons.

The effects of a short train of electrical impulses applied to the central stump of a cut vagus nerve at various moments of the central respiratory cycle were studied in 28 rabbits and 3 baboons. The animals were anaesthetized (halothane), vagotomized, paralyzed and artificially ventilated. Stimulation in inspiration elicited always an inhibitory effect (latency 8-9 ms) the magnitude of which increased towards the end of inspiration. The amplitude and duration of inhibition increased also with the frequency of impulses and/or the duration of the volley. Stimulation in expiration shortened this phase after latency being shorter towards the end of expiratory pause. It is suggested that excitation of thin myelinated vagal fibres has a facilitatory effect on the inhibitory response to information being conducted along thick myelinated fibres during inspiration.

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Generation of respiratory pattern in the rabbit -- brainstem transections revisited.

The effects of unilateral transection of the lower brainstem on the generation of central respiratory rhythm and its amplitude were studied in halothane anesthetized, vagotomized, paralyzed and artificially ventilated rabbits. Transections involving N. VII or rostral part of N. r VII elicited apneustic pattern of discharge in both phrenic nerves. Lesions made at more caudal levels (1.5-3.5 mm rostral to obex) restored a more normal pattern of discharge as far as frequency is concerned, but reduced the amplitude, particularly in the ipsilateral phrenic nerve. Sections below the obex abolished the activity of the ipsilateral phrenic n. Since classical midpontine sections did not, elicit apneustic discharge, it is possible that this pattern is produced by modifications in the number and functional connections of inspiratory-inhibitory neurons.

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Effects of reversible elimination of some bulbar structures on the generation of respiratory pattern in rabbits.

The regions of (i) nucl. n. VII (N. VII), (ii) nucl. retrofacialis (N. r. VII), (iii) nucl. Ambiguus (A.c) and (iv) nucl. ret. parvocellularis (n.rp) were explored with microelectrodes and then the active sites were injected with 5 microliters of lignocaine. The activity of both phrenic nerves, blood pressure and end-tidal CO2 percent were recorded throughout the experiment. Blockade of the n.VII region elicited apneustic discharge in both phrenic nerves; blockade of N.r.VII gave variable frequency responses but always reduced phrenic amplitude of discharges; microinjection of lignocaine into the region of A.c. invariably accelerated central respiratory rhythm, the amplitude of discharges being reduced predominantly contralaterally to the injection site; blockade of the R.pc elicited a dramatic prolongation of expiratory pause, decrease in amplitude and rate of rise of phrenic activity. All effects disappeared within 30 min after injection and histological examinations revealed only minor lesions at the sites of injections. It is concluded that the respiratory neurons of the medulla form a complex, strongly interconnected network.

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Respiratory responses to stimulation of afferent vagal fibres in rabbits.

In the experiments with 43 paralyzed rabbits ventilated artificially under general anaesthesia with halothane the effect of electrical stimulation of the central end of the vagus nerve on respiratory pattern was investigated. The analysis of respiratory responses to varying parameters of stimulation, and comparison of results with the experiments in which stimulation of pulmonary receptors was used, confirmed the view that the activities transmitted along the thick myelinated fibres of the vagus nerve exerted an inhibitory effect on the generation of inspiratory activity, while the activities transmitted along thin myelinated fibres accelerated the respiratory rate. The integrative processes transforming the activity of thick fibres had a time constant shorter by two orders than the integration of responses to stimulation of thin fibres.

Afferent Pathways↗