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K Budzińska

Publications and source records attributed to K Budzińska.

At least 19 recordsLinked to original sources

Short-term depression of inspiratory activity following tonic vagal stimulation.

This study tested the role of inhibitory neurotransmission in the glutaminergic control of short-term depression (STD) of the inspiratory activity initiated by sustained stimulation of the vagus nerve in anesthetized and vagotomized cats. STD, calculated from the integrated phrenic nerve signal, lasted longer when glutaminergic neurotransmission was inhibited by ketamine, a NMDA receptor antagonist. Application of picrotoxin, a GABAA receptor antagonist, reversed the effect of ketamine and shortened the STD duration below that present in the control condition. The results showed that alternation of the neural excitability by antagonists of excitatory and inhibitory neurotransmission modulates the STD of inspiratory activity, evoked by vagal stimulation. The STD depends on the state of neural excitability and is easier accomplished when the excitability is on the high side.

Animals↗

Neurotransmitter mechanisms in the enhancement of the hypoxic ventilatory response by antecedent hyperoxia in the anesthetized rat.

A brief period of antecedent oxygen breathing enhances the ventilatory response to hypoxia. The mechanisms of this phenomenon are uncertain and have been variably linked to the central glutamatergic or nitrergic pathways. In the present study we put a question of how blockade of either neurotransmitter pathway would compare with the concurrent blockade of them both in terms of the enhancement of posthyperoxic hypoxic ventilation. The study was performed on the anesthetized, vagotomized, spontaneously breathing rats divided into the following experimental groups: control NaCl-treated, glutamate blocker 2-amino-5-phosphonopentanoic acid (AP5)-treated, nitric oxide synthase blocker 7-nitroindazol (7NI)-treated, and AP5+7NI-treated. The protocol consisted of measuring the ventilatory response to 12% O2, a steady- state poikilocapnic hypoxia, undertaken in three consecutive conditions in each animal: the initial control, 25 min after injection of a given chemical agent, and then after a 15-min period of oxygen breathing. Respiration was evaluated from the diaphragmatic EMG signal. We found that the posthyperoxic hypoxic ventilatory enhancement was but partially dampened by either AP5 or 7NI. Concurrent administration of the two blockers further diminished, but did not abolish, the hypoxic ventilatory enhancement. We conclude that although the glutamate-NO system accounts for an appreciable part of the posthyperoxic hypoxic ventilatory enhancement, other, as yet unclear, mechanisms contribute as well. These mechanisms may be worth exploring given the substantial enhancing effect the antecedent oxygen has on hypoxic hyperventilation.

2-Amino-5-phosphonovalerate↗

Biphasic effect of ethyl alcohol on short-term potentiation of the respiratory activity in the rabbit.

This study investigated the effects of systemic alcohol injections on respiratory activity and short-term potentiation (STP) of the phrenic nerve and hypoglossal nerve activities, evoked by electrical stimulation of the superior laryngeal nerve (SLN), in anesthetized, paralyzed, and artificially ventilated rabbits. Alcohol, in a dose of 500 mg/kg, given singly or in cumulative fractions of 100mg/kg, depressed hypoglossal activity with little or no effect on phrenic activity. SLN stimulation inhibited both phrenic and hypoglossal activities and this effect remained unchanged by either way of alcohol administration. After cessation of stimulation, hypoglossal activity increased above the control level and slowly declined to the baseline, showing signs of STP. The amplitude and duration of the hypoglossal STP decreased following a single dose of alcohol. Cumulative fractions of the alcohol dose evoked a biphasic effect on the respiratory STP. In a lower range, alcohol enhanced the hypoglossal STP and tended to increase the duration of the phrenic STP. This effect gradually declined with increasing cumulative dose of alcohol and finally reversed to the inhibition of the STP of both nerves. The results demonstrate a dose-dependent biphasic effect of alcohol on the induction and maintaining of the hypoglossal STP. A reduction in STP, together with hypoglossal activity depression following alcohol accumulation, may contribute to the facilitation of upper airway obstruction by alcohol.

Action Potentials↗

Divergent effects of bicuculline and picrotoxin on ketamine-induced apneustic breathing.

This study tested the potential role of inhibitory neurotransmission in the mechanism of apneustic respiration evoked by ketamine, an NMDA receptors antagonist. In the experiments performed in anesthetized, paralyzed, and ventilated cats, ketamine, in a dose of 0.5 mg/kg, was administered before and after GABA(A) receptor blockade with picrotoxin or bicuculline; all agents were given intravenously. Ketamine elicited a transient, hourlong apneustic respiration consisting of an increase in inspiratory duration and a decrease in inspiratory neural amplitude. After prior administration of picrotoxin, but not bicuculline, the maximum apneustic-like prolongation of inspiration evoked by ketamine was considerably reduced. The results suggest that the GABA receptor subunits specifically sensitive to picrotoxin play a role in shaping the ketamine-induced apneustic breathing.

Animals↗

Hypoglossal and phrenic nerve responses to changes in oxygen tension during picrotoxin-induced seizures in the rat.

The aim of this study was to examine the response of phrenic and hypoglossal motor outputs to hyperoxia and 11% hypoxia during picrotoxin-induced seizures. Adult rats were anesthetized with a mixture of urethane with alpha-chloralose. The animals were bilaterally vagotomized, paralyzed, and artificially ventilated. Picrotoxin was administered intravenously in a cumulative dose until seizures occurred. The response to changes in oxygen tension was studied after the convulsive dose of picrotoxin and compared with the baseline level. The results show that the picrotoxin-induced seizures evoked a complex respiratory response that consisted of an augmentation of phrenic and hypoglossal nerve activities and irregular disturbances in phasic respiratory discharges. The excitation of the hypoglossal activity appeared earlier and showed a more irregular pattern than that of the phrenic activity. Hyperoxia elicited a similar decrease in neural respiratory outputs during the control and seizure conditions, suggesting the unaltered peripheral chemoreceptor mechanism. In the pre-seizure condition, hypoxia caused an initial excitation of the phrenic and hypoglossal outputs followed by some decline of the effect. During seizures, the striking effect of hypoxia was a decrease of the respiratory rate. A biphasic response to hypoxia was maintained in the hypoglossal activity due to stimulation of the hypoglossal amplitude. In contrast, in the phrenic activity the excitatory phase of hypoxia was absent and depression ensued. The mechanism underlying the facilitation of hypoxic respiratory depression during seizures is discussed.

Animals↗

Changes in short-term potentiation of hypoglossal activity by modulators of nitric oxide production in the rabbit.

Stimulation of the superior laryngeal nerve (SLN) causes a potentiation of hypoglossal nerve activity persisting after cessation of stimulation. The mechanism of this phenomenon is uncertain. We investigated a potential role of the nitric oxide (NO) pathway in modulation of the after-effects of SLN stimulation on phrenic and hypoglossal activity in rabbits. L-Arginine, a substrate for NO synthesis and NG-Nitro-L-Arginine (L-NNA) an inhibitor of NO synthase (NOS), were administered systemically. L-Arginine and L-NNA alone caused small changes in respiratory activity. During pre-treatment with NO precursor the amplitude and duration of hypoglossal potentiation evoked by SLN stimulation were reduced. Systemic NO synthase inhibition partially reversed these effects of L-Arginine. The results showed that interference with NO production by NO substrate and NOS inhibitor modulates the effects of SLN stimulation on hypoglossal activity. Nitric oxide might be a negative modulator of the transmission of short-term potentiation (STP) in hypoglossal activity.

Action Potentials↗

[Diaphragmatic electromyogram and respiratory pattern after unilateral and bilateral partial denervation of the diaphragm in the cat].

In the present study we investigated the mechanism of early respiratory compensation of partial paralysis of the sternal and lateral diaphragm due to an unilateral or bilateral section of the C5 rootlet of the phrenic nerves in anesthetized cats. Compensatory effects were evaluated from the recordings of the bilateral diaphragmatic EMGs, neural respiratory pattern and ventilation. The results of the study demonstrate that successive C5 denervation of the diaphragm caused a decrease in the ipsilateral diaphragmatic EMG. Bilateral C5 section evoked an up to 10 percent decrease in minute ventilation. The compensation of the unilateral and then bilateral partial impairment of the muscle function was achieved always by an increase in the neuromuscular projection to the currently contralateral diaphragm. Neural mechanisms of compensation involve a general increase in the respiratory drive, expressed mostly as an increase in the frequency of breathing. The contribution of afferent respiratory muscles to these mechanisms is likely.

Animals↗

The role of raphe and tractus solitarius neuronal structures in the modulation of respiratory pattern in rabbits.

We studied the effects of MNR stimulation on phrenic (Phr) electroneurogram and external intercostal muscles (EI) electromiogram in spontaneously breathing rabbits. Additionally, experiments were performed before and after lignocaine blockade of nucleus tractus solitarii (NTS) to determine whether the information from MNR is transmitted via NTS neurones. The completeness of the blockade of NTS region was checked by studying the Hering-Breuer reflex. MNR was stimulated at the level 2-7 mm rostral to the obex. Stimulation at the rostral part of this region produced inhibition of phasic inspiratory activity, whereas stimulation in the caudal part elicited tonic activity throughout the respiratory cycle. These effects were more pronounced on EI than Phr. Responses to MNR stimulation were attenuated after lignocaine blockade, suggesting that the neurons located in NTS take part in the transmission of the modulatory information from the MNR to respiratory motoneurones.

Anesthetics, Local↗

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↗

Short-latency phrenic response to vagal stimulation after midsagittal lesion of the medulla in rabbit.

The effect of midsagittal lesions of the medulla on the phrenic nerve output and the central transmission of the vagal input were studied. The rabbits were anaesthetized with a mixture of chloralose with urethane, paralysed and artificially ventilated. Both vagi were sectioned in the neck and one of them was prepared for electrical stimulation of its proximal end. Lesions of the medulla were performed in steps and at each stage the short-latency phrenic response to a single electrical shock applied to the vagus was studied. The results indicate that, at the levels 1 to 5 mm rostra1 to the obex and 3 mm in depth from the dorsal medullary surface, there is a maximal density of crossing connections important for transmission of the descending respiratory activity, synchronization of the respiratory activity generated by left and right part of the medulla and transmission of the vagal signal.

Animals↗

Effects of graded focal cold block in the solitary and para-ambigual regions of the medulla in the cat.

Unilateral focal cold blocks in the region of the nucleus tractus solitarius and the dorsal respiratory group of neurons, DRG, of anaesthetized cats consistently caused apneustic-type breathing. There was no concomitant change in the initial rate of rise of inspiratory activity. The apneustic prolongation of inspiratory duration, TI, was most pronounced in, but was not confined to, the DRG. The apneustic effects were more marked after vagotomy. In cats with intact vagus nerves being given artificial ventilation, focal cooling at certain sites of the DRG region could produce 'unlocking' of the respiratory rhythm from that of the respiratory pump. At other sites in this region, focal cooling could selectively block the effects of the inspiration-facilitating reflex induced by deflation without blocking the inspiration-inhibiting Hering-Breuer reflex. Unilateral focal cold blocks in the region of the intermediate part of the ventral respiratory group of neurons, VRG, generally caused depression of the rate of rise of inspiratory activity, but almost never apneustic effects. All effects of unilateral focal cooling both in the DRG and VRG were bilaterally symmetrical. No systematic differences between the effects on phrenic and external intercostal inspiratory activity were found in response to focal cooling either of the DRG or VRG suggesting that differential control of phrenic and external intercostal motoneurons is not exerted mainly at the level of these medullary structures. The results suggest that the DRG and VRG areas exert somewhat different effects on the respiratory pattern: DRG appears to be more concerned with integration of vagal and other inputs contributing to the inspiratory off-switch mechanisms which, however, are not confined only to the DRG. The VRG inspiratory mechanisms, on the other hand, appear to be more involved in the gain control of the inspiratory output intensity.

Animals↗

Effects of graded focal cold block in rostral areas of the medulla.

Unilateral focal cold blocks (20 degrees C) in structures located ventrolaterally in rostral medulla consistently caused apnoea or deep depression of inspiratory motor output. The inhibitory effect could be correlated with the cooling temperature. Apnoeic response occurred either with complete absence of any inspiratory activity or combined with low level tonic inspiratory motor activity ('tonic apnoea'). The appearance of apnoea was CO2-independent, whereas the tonic component of the latter increased with increasing levels of PCO2. The results suggest that the structures in the deep, ventro-lateral aspect of rostral medulla, from which apnoea can be induced, correspond partly to the nucleus paragigantocellularis lateralis (nPGL) and the nucleus preolivaris. These structures appear to be relevant for the drive inputs necessary for respiratory rhythmogenesis. Unilateral focal cooling in the rostral medulla, including the 'Bötzinger Complex', caused increments in respiratory rate both in vagotomized and non-vagotomized animals. The increase in respiratory rate in response to cooling in the region of the 'Bötzinger Complex' was combined with either an enhancement or some depression of respiratory motor output. This area in the rostral part of the ventral respiratory group (VRG) seems not to be crucial for respiratory rhythmogenesis, but to play a role in determining both the intensity and timing of the respiratory activity. All effects of unilateral cold block were bilaterally symmetrical.

Animals↗

Release of expiratory muscle activity by graded focal cold block in the medulla.

Disinhibition or 'release' of expiratory muscle activity in response to focal cooling of various medullary structures was of two kinds: (1) release of rhythmic expiratory activity even when no such activity was recruited in the control situation and (2) release of tonic activity in the 'expiratory' muscles. Release of rhythmic expiratory activity was mainly elicited by focal cooling of structures in the intermediate part of the medulla and release of tonic activity was preferentially induced by cooling rostroventral structures, although a considerable overlap did occur. Release of rhythmic expiratory activity was not related to any changes in expiratory time (TE) or to any associated variations in the pattern of inspiratory activity. It showed a marked increase with increasing levels of PCO2. The release of tonic activity was not CO2-dependent. Both types of effects could be mimicked by focal microinjections of lignocaine and were reflected by corresponding changes in activity of a majority of the expiration-related neurons. These results suggest that complex and widespread neural substrates subserve the control of the intensity of rhythmic expiratory activity and of the tonic activity of the abdominal and intercostal muscles. These neural mechanisms can apparently operate independently from those controlling the inspiratory activity. The release of the tonic activity observed in the 'expiratory' muscles might reflect a disinhibition of mechanisms involved in non-respiratory functions of expiratory muscles.

Animals↗

Response of respiratory motoneurons to release from vagal inhibition in the rabbit.

Long-lasting effects of vagal input on phrenic (Phr) and external intercostal (EI) motoneuronal output were studied on 16 anesthetized rabbits breathing spontaneously or paralysed and ventilated by a phrenic nerve-driven pump. Withholding of ventilation by tracheal occlusion or by switching off the servorespirator maintained for seven breaths evoked a progressive increase of Phr and EI from breath to breath. This effect was more evident in animals ventilated by servo- respirator. The higher was the gain of the pump (volume-to-phrenic signal ratio) before the maneuvre, the bigger was the rate of increase of the tidal phrenic amplitude from breath to breath at all CO2, levels tested. Vagotomy strongly depressed or eliminated this effect. We conclude that with intact vagus nerve the increase of respiratory motoneuronal output was only partialy due to the gradual increase in chemical drive when ventilation was stopped. The character of the response indicates the existence of a long-lasting component of the Breuer-Hering reflex. Splitting the medulla abolished this prolonged response while preserving the inspiratory vagal inhibition indicates that the neuronal pathways crossing the midline of .the medulla are important for the effect.

Animals↗

Short-latency phrenic response to electrical vagal stimulation in rabbits.

The response of the phrenic motoneurones to single shock stimulation of- afferent vagal fibres during inspiration was studied in rabbits. The rabbits were anaesthetized with halothane, paralysed, artificially ventilated and bilaterally vagotomized. To improve the detection of the response on the non-integrated efferent phrenic activity in the presence of background discharge, 64 to 128 single responses were averaged using a sampling time of 0.1 ms. No short-latency responses were obtained to single shock at threshold strength for the coarsest afferent vagal fibres. With increased stimulus strength activating also some finer myelinated fibres, as evidenced from the effect of low-frequency stimulation on the breath duration, a short-latency inhibition followed by an enhancement was observed bilaterally. The average latency of the inhibition was 8.5 ms. The results differ from these which can be obtained in cats.

Animals↗