Biomedical subjects

F L Eldridge

Publications and source records attributed to F L Eldridge.

At least 19 recordsLinked to original sources

PubMed1992

Neural respiratory responses to cortically induced seizures in cats.

Seizure activity can lead to profound respiratory stimulation in spontaneously breathing animals with intact respiratory feedback mechanisms (Paydarfar et al., Am. J. Physiol. 260, R934, 1991). The present study was designed to test the hypothesis that peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea. Studies were performed in 16 anesthetized, vagotomized, glomectomized cats whose end-tidal PCO2 (PETCO2) was kept constant. Integrated phrenic nerve activity was used to represent respiration. Seizures were induced by injection of penicillin into the parietal cortex and electrocorticographic (ECoG) and biceps femoris nerve activities, arterial pressure, airway PCO2 and brain temperature were recorded continuously. Progressive seizure activity was associated with progressive increases of respiratory frequency and peak phrenic activity, despite constancy of PETCO2 and brain temperature. Patterns of entrainment were identified among ECoG spikes, biceps femoris nerve and phrenic nerve activities. Phrenic nerve activity became highly irregular during generalized ictal seizures and ceased to respond to changes of PETCO2. Acute intercollicular decerebration in all experiments resulted in normalization of respiratory rhythm even while ictal ECoG activity continued. We conclude that stimulation of breathing during seizures occurs in the absence of respiratory feedback mechanisms. The findings suggest that an important cause of the respiratory response is a feedforward mechanism, whereby activation of subcortical structures above medulla and pons results in stimulation of breathing.

Animals↗

PubMed1992

Respiratory-associated rhythmic firing of midbrain neurons is modulated by vagal input.

We recorded phrenic nerve activities and single unit firings of mesencephalic neurons in 19 decerebrate, paralyzed and ventilated cats, in which the spinal cord had been transected at C7-T1 and carotid sinus nerves cut but vagus nerves left intact. After we had found neurons with respiratory-associated rhythmic activity, we tested the effect of changing pulmonary vagal input by (1) stopping and restarting the ventilator; (2) changing the ventilator's tidal volume; (3) progressively cooling the vagus nerves to 6-7 degrees C; and (4) vagal section. All methods of testing yielded results that showed that vagal input, probably from pulmonary stretch receptors, tonically inhibits the respiratory-associated firing of the mesencephalic neurons by a direct mechanism that is independent of a vagal effect on medullary respiratory drive. We have suggested that these neurons are involved in the mechanism that conveys information about respiration to the cortex where it may be interpreted as the sensation of dyspnea. If so, movement and increased expansion of the lungs can be expected to lessen the sensation.

Animals↗

PubMed1992

Respiratory-associated thalamic activity is related to level of respiratory drive.

We recorded phrenic nerve activity and thalamic single unit firing in unanesthetized, suprathalamically decerebrated, paralyzed and ventilated cats, in which vagi and carotid sinus nerves (CSN) had been ablated. Seventy-six (14%) of 545 neurons in regions of the thalamus related to the ascending reticular system, which had been tonically firing at low respiratory drives, developed rhythmic increases of firing associated with each respiration when drive had been increased by CSN stimulation or hypercapnia. The increases of neuronal firing occurred in late inspiration/post-inspiration but sometimes lasted into expiration; the magnitude of change was graded according to the magnitude of respiratory activity. Thalamic neurons also fired with a rhythm related to ventilator-induced chest expansion, some units showing both the respiratory-associated and the ventilator-related rhythms. Simultaneously recorded mesencephalic and thalamic neurons developed similar rhythms when drive was increased. We suggest that these neuronal activities reflect the conveyance of information about respiration to the cortex, where it may lead to the sensation of dyspnea and perhaps to arousal.

Action Potentials↗

PubMed1991

Development of short-term potentiation of respiration.

Development of short-term potentiation (STP) of respiration, which leads to the respiratory 'afterdischarge', was studied in anesthetized, paralyzed, vagotomized and glomectomized cats. Phrenic nerve activity was used as an index of respiratory output. Respiratory output was increased and the potentiating mechanism activated by electrical stimulation of a carotid sinus nerve (CSN). Development of STP was determined from the magnitude of potentiation after various durations (0 to 60 sec) of stimulation. The average time constant (TC) for the development of the potentiation was 9 sec, whereas the TC for its decay (afterdischarge) was 46.1 +/- 3.9 sec. The magnitude of potentiation is dependent upon the number of pulses in the stimulus train. We conclude that the development of short-term potentiation of respiration is relatively slow but much faster than the decay, or afterdischarge. We suggest that the slow increase of respiration during a stimulation and the decay afterwards are due to a common mechanism, short-term potentiation of neural activity in respiratory control pathways.

Action Potentials↗

PubMed1991

Anesthesia affects respiratory and sympathetic nerve activities differentially.

Phrenic and cervical sympathetic nerve responses to hypercapnia were examined before and after anesthesia in twelve midcollicularly decerebrated, vagotomized, glomectomized, paralyzed and ventilated cats. We measured responses of integrated phrenic and cervical sympathetic nerve activities to increases in end-tidal PCO2 (PETCO2) from apneic threshold to approximately 30 torr above threshold. All cats were studied first in the unanesthetized state. Six cats were then restudied after a quarter of a usual dose of chloralose/urethane (10 mg/kg and 62.5 mg/kg, respectively) and then after half the usual dose of chloralose/urethane (20 mg/kg and 125 mg/kg). The other six animals were restudied after quarter of a standard dose of pentobarbital (9 mg/kg), after half the standard dose (18 mg/kg) and then after the full (35 mg/kg) dose. Both anesthetic agents led to significant increases in apneic thresholds for both phrenic and sympathetic nerve activities. These agents also caused dose-dependent decreases in peak, tonic and respiratory-related sympathetic nerve activities. Peak (tidal) phrenic nerve activities, in comparison, were much less affected by the anesthetic agents. CO2 response curves showed that both of these anesthetic agents depressed, at any given level of PETCO2, respiratory-related sympathetic nerve responses more than the responses found in the phrenic nerve. We conclude that the relations between peak, tonic (i.e. between phasic bursts) and respiratory-related sympathetic nerve activities and phrenic nerve activity can be altered by anesthesia.

Anesthesia↗

PubMed1991

Respiratory-associated rhythmic firing of midbrain neurones in cats: relation to level of respiratory drive.

1. We recorded phrenic nerve activities and single unit firing of mesencephalic neurones in unanaesthetized supracollicularly decerebrated, paralysed and ventilated cats, in which vagi and carotid sinus nerves had been ablated. We made these measurements first at low levels of respiratory drive associated with normal PCO2 levels, then with increased respiratory drive and levels of phrenic activity produced by hypercapnia or by carotid sinus nerve stimulation. 2. We found that at least a quarter of the neurones in the central tegmental field of the mesencephalon, which were irregularly tonic or silent at low respiratory drives, developed a rhythmic increase of firing associated with each respiration. There appeared to be a threshold at about 50% of maximum respiratory activity, below which the respiratory-associated rhythm did not occur. Above this level, neuronal firing increased in graded fashion with increasing magnitude of respiratory activity. The latency from onset of phrenic activity to onset of increased neuronal firing was quite long (1.0 s) at drives just above the threshold but shortened to as little as 0.3 s as drive increased towards its maximum. 3. Cutting the spinal cord at C1-C2 had no effect on the ability of increased respiratory activity to generate a respiratory-associated rhythm in mesencephalic neurones. 4. Short-lasting anaesthesia with the agent Saffan caused mesencephalic neurones to lose the respiratory-associated rhythm with little change in phrenic activity and no change in respiratory cycle timing. 5. We also found a mesencephalic response to ventilator-induced chest expansion. The latency of the response from onset of expansion, indexed by fall of airway PCO2, to onset of neurone firing was shorter (0.2 s) than that found with the respiratory-associated rhythm. In seventeen neurones we found both the respiratory-associated rhythm and the independent ventilator-associated rhythm. 6. We interpret our findings to show that the respiratory-associated rhythmic firing of midbrain neurones is not primarily involved in generation or modulation of the motor function of the respiratory oscillator. We believe, instead, that these neurones are part of a sensory pathway conveying information about the magnitude of central neural respiratory drive, as well as spinally transmitted information from receptors in the chest wall, to thalamus and cortex. We suggest that the sensation ultimately generated may be that of 'air hunger' or dyspnoea.

Action Potentials↗

PubMed1991

Respiratory responses to focal and generalized seizures in cats.

We studied the effects on breathing of seizures induced by focal injection of penicillin G into the parietal cortex in 13 anesthetized cats. Electrocorticograms, ventilation, end-tidal PCO2, and intrapleural and arterial pressures were monitored; changes of these variables were related to the stages of motor seizure. The first respiratory responses, tachypnea and hyperpnea, usually occurred before any peripheral muscular contractions developed. Progression of the seizure was always accompanied by further tachypnea and hyperpnea. The hyperpnea associated with all stages of seizure activity resulted in hypocapnia, which was sustained even during prolonged tonic-clonic motor convulsions that caused a threefold increase of metabolic rate. The extreme tachypnea of tonic generalized convulsions led to increased end-expiratory lung volume because of dynamic hyperinflation associated with very short expiratory durations in the tonic phase. We suggest that the profound effects of seizures on respiration are by feedforward mechanisms from the cortical focus itself and from subcortical circuits, such as hypothalamus, that become involved during seizure propagation and generalization. Peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea.

Animals↗

PubMed1989

Role of endogenous adenosine in recurrent generalized seizures.

We induced generalized seizures by cortical injection of penicillin in anesthetized, paralyzed cats. After they had developed recurrent ictal-interictal ECoG cycling and fictive tonic-clonic motor convulsions (status epilepticus), we studied the effect of systemically administered neuropharmacological agents on the seizure cycling. Antagonists of adenosine receptors, theophylline and 8-cyclopentyltheophylline, increased the cycle period due to marked prolongation of duration of ictal discharge, often to more than 30 min. Dipyridamole, an inhibitor of adenosine reuptake, lengthened the interictal phase of the seizure with no effect on ictal duration. Antagonists of gamma-aminobutyric acid and opioid peptides had no effect on either ictal or interictal phases nor did the nonspecific neural excitant, doxapram. These findings suggest that a major mechanism of ictal-interictal cycling during status epilepticus is the alternating accumulation during the ictal phase and clearance during the interictal phase of the inhibitory neurochemical, adenosine.

Adenosine↗

PubMed1989

Desynchronized respiratory rhythms and their interactions in cats with split brain stems.

1. The effects on activities and rhythms of the two opposing phrenic nerves (C5 roots) of mid-line sagittal splitting of the medulla were determined in anaesthetized or decorticate, vagotomized, paralysed and ventilated cats. 2. Splitting the medulla above the obex led to marked decreases of phrenic activity on both sides, but no desynchronization of the two phrenic rhythms occurred. Further splitting to more than 3 mm below the obex led to desynchronized phrenic rhythms in fourteen of the fifteen animals that survived the necessary surgery, although it was often necessary to increase respiratory drive by means of hypercapnia, stimulatory drugs or electrical stimulation of the mesencephalon to cause the rhythms to occur. 3. When only the brain stem had been split, the two desynchronized rhythms showed interactions that led to modulations of amplitude of phrenic bursts, both being larger when in phase than when out of phase. In addition each side modulated the rhythm of the opposite side, demonstrating a 'magnet' effect. 4. Both types of modulation were eliminated after additional splitting of the spinal cord at the level (C5-C6) of the phrenic motoneurone pools. 5. Potential explanations for the amplitude modulations include cross-over of activity from one phrenic motoneurone pool to the opposite side and cross-over from the medulla of one side to the opposite phrenic motoneurone pool at the phrenic level. 6. Since the rhythm generators were independent in our preparation and located in the split halves of the medulla and since peripheral sensory feed-back was not important in these paralysed animals, we propose that the phase modulations must be due to a corollary discharge, an afferent feed-back driven by phrenic motoneurone activity that crosses the mid-line at C5-C6, ascends to the brain and affects respiratory rhythm in the opposite medullary half.

Animals↗

PubMed1989

Phase resetting of respiratory rhythm: effect of changing respiratory "drive".

We studied the effect of changing drive on resetting of respiratory rhythm in anesthetized cats and in a model (Van der Pol) of a limit-cycle oscillator. In cats, rhythm was perturbed by brief mesencephalic stimuli. Stimulus time in the cycle (old phases) and times of onset of rescheduled breaths (cophases) were measured. Previous study [Paydarfar and Eldridge, Am. J. Physiol. 252 (Regulatory Integrative Comp. Physiol. 21): R55-R62, 1987] showed distinct types of phase resetting that depended on strength of stimuli. In this study, stimulus strength was kept constant, but respiratory drive was changed by increasing PCO2, by stimulating carotid sinus nerve, or by cooling intermediate areas of ventral medulla. Type 0 (strong) resetting occurred when respiratory drive was low, type 1 (weak) resetting when drive was high, and a phase singularity when drive was intermediate. Phase-resetting patterns generated by the model showed the same behavior when a drive parameter was changed. The findings support the idea that continuous limit-cycle dynamics underlie generation of respiratory rhythm. Increased respiratory drive, by increasing size of the limit cycle, reduces functional effectiveness of the same perturbing stimulus in causing phase resetting.

Animals↗

PubMed1989

Buspirone, an anxiolytic drug that stimulates respiration.

The recently released drug buspirone is an anxiolytic agent that appears not to have the sedating effects of barbiturates and benzodiazepines, both known to have respiratory depressant effects. Because of its increasing clinical use, we desired to study the effects of buspirone on respiratory control. We therefore determined central neural respiratory responses, measured from phrenic nerve activity, after intravenous administration in paralyzed, vagotomized, and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. The responses were compared to the effects of the sedating tranquilizer diazepam. Buspirone had a dose-dependent stimulatory effect on respiratory output primarily through an increase of tidal activity but with an increase of frequency in some animals. Associated with this was a shift of the apneic threshold to a lower level of PCO2 without a change of slope or shape of the CO2 response curve. In contrast, diazepam led to a depression of respiration and a shift of the apneic threshold to a higher PCO2. The findings indicate that buspirone does not have the typical neural respiratory depressant actions of diazepam but instead stimulates respiration. Although the findings will need to be shown to apply to human beings, they suggest that buspirone may be a useful drug to treat anxiety in patients without causing undesirable respiratory depression.

Animals↗

PubMed1987

Effects of hyperoxia on medullary ECF pH and respiration in chemodenervated cats.

The effects of transitions from air-breathing to hyperoxia (100% O2), and the reverse, on respiration (phrenic activity) and on medullary extracellular fluid (ECF) pH, or hydrogen ion concentration [H+], were studied in 8 anesthetized, paralyzed, vagotomized and glomectomized cats whose end-tidal PCO2 was kept constant. The transition from air to hyperoxia (7 cats) led to a small (1.23 nmol/L [H+], 0.010 pH unit) acidic shift of medullary ECF and a 24% increase of neural tidal and minute respiratory activity with no significant change of frequency. Opposite changes of approximately equal magnitude followed the transition from hyperoxia to air (8 cats). We show that the slopes of the respiratory responses to changing ECF [H+] in the present study are not different than the slopes with CO2-induced changes of ECF [H+] in 25 other cats. Our findings indicate that most, if not all, of the respiratory increase after hyperoxia is due to accumulation of CO2 and H+ in medullary ECF that act on the central chemoreceptors. We suggest that decreased medullary blood flow and the Haldane effect are the main mechanisms causing the rise of medullary PCO2 and stimulation of breathing.

Animals↗

PubMed1987

Dynamics of medullary hydrogen ion and respiratory responses to square-wave change of arterial carbon dioxide in cats.

1. The dynamics of changes of medullary extracellular fluid (ECF) hydrogen ion concentration ([H+]) and respiration, measured as integrated phrenic nerve activity, were determined in anaesthetized, paralysed, vagotomized and glomectomized cats. ECF [H+] was measured directly by means of a small (2 mm diameter) glass pH electrode placed on the ventral surface of the medulla. The variables were measured continuously after a step change of arterial PCO2 produced by abruptly starting or stopping an infusion of hypercapnic fluid into the aortic arch. 2. Alteration of pH in the descending thoracic aorta at the onset or offset of infusion was complete within 1.5 s after the change began, indicating that it was nearly square wave in form. 3. In sixteen experiments, ECF [H+] began to fall within 2 s of offset of infusion, reflecting aortic-medullary circulation time. Thereafter, ECF [H+] decreased to a stable level over the next 5 min; the curve describing the decrease consisted of two exponential functions, one with a time constant (tau) of 9.5 +/- 0.6 s and a second with a tau of 53 +/- 3 s. 4. We interpret the findings at the offset of CO2 infusion in terms of CO2 wash-out from the medullary ECF. The slow function is associated with wash-out during stable medullary blood flow that develops after 1 min. The early fast function is associated with the decreasing medullary blood flow that occurs during the first minute after change from arterial hypercapnia to normocapnia. 5. We have estimated medullary blood flow using a mathematical model incorporating the two functions. The values obtained are consistent with those in the literature where other methods have been used. Changes of blood flow following the step change of CO2 are fairly rapid, half of the response occurring in 13 s. 6. The change of respiratory activity lags the change of stimulus expressed by [H+], throughout the recovery period and respiration requires up to 8 min to reach a stable level. We attribute this slow response to slow central neural respiratory dynamics, the respiratory after-discharge.

Action Potentials↗

PubMed1987

Spinal inhibition of phrenic motoneurones by stimulation of afferents from leg muscle in the cat: blockade by strychnine.

1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in paralysed high (C1) spinal cats whose phrenic nerve activity was evoked by activation of the intercostal-to-phrenic reflex. End-tidal PCO2 was maintained at a constant level by means of a servo-controlled ventilator. 2. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve uniformly caused inhibition of phrenic activity evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued, and there was a post-stimulus augmentation of phrenic activity. 3. Pre-treatment with subconvulsive doses of strychnine, an antagonist of the neurotransmitter glycine, partially or completely blocked the inhibitory effects on phrenic activity of muscle-afferent stimulation. The blockade was reversible with time. 4. Pre-treatment with a subconvulsive dose of bicuculline, an antagonist of the neurotransmitter gamma-aminobutyric acid (GABA), had no effect on the inhibitory mechanism. 5. We conclude that glycine is an important transmitter of the inhibition of phrenic motoneurones induced by muscle-afferent stimulation, but that GABA is not involved in this inhibitory mechanism.

Action Potentials↗

PubMed1987

Phase resetting and dysrhythmic responses of the respiratory oscillator.

This study explores resetting of respiratory rhythm by facilitatory perturbations. The midbrain reticular formation and periaqueductal gray matter were electrically stimulated to evoke facilitation of phrenic nerve activity in nine anesthetized, vagotomized, and glomectomized adult cats. The animals were paralyzed and servo-ventilated to keep end-tidal PCO2 constant. Brief midbrain stimuli were given at various times in the respiratory cycle and the times of onset of rescheduled breaths after stimulation were measured. A plot of phase resetting as a function of stimulus strength and time of delivery defined a helicoid surface. The axis of this helicoid identified a unique stimulus which, when given at the inspiratory-expiratory transition, resulted in unpredictable resetting of respiratory rhythm. This stimulus had a strength that was intermediate to that which identified types 1 and 0 resetting. In one experiment, the singular stimulus often initiated a breath having prolonged inspiratory activity; resumption of the normal rhythm was delayed significantly (P less than 0.01). We conclude that the dysrhythmias observed in this study represent the respiratory oscillator's phase singularity.

Animals↗

PubMed1987

Diencephalic regulation of respiration and arterial pressure during actual and fictive locomotion in cat.

The purpose of this study was to examine by experimentation the hypothesis that the respiratory and circulatory responses during exercise are attributable to command signals that emanate from the suprapontine brain. We studied the relations between locomotion (exercise) and phrenic nerve activity and arterial pressure in cats that walked or ran on a treadmill and in animals during fictive locomotion, i.e., locomotor activity in motor nerves to legs. Anesthetized cats with intact brains and unanesthetized decorticated cats were used. All preparations exhibited spontaneous actual and fictive locomotion. Electrical stimulation or microinjection of picrotoxin, a GABA antagonist, of the subthalamic locomotor areas always caused locomotion to develop. Phrenic nerve activity and arterial pressure increased in proportion to the level of locomotor activity despite control or ablation of feedback signals from chemoreceptors and vagal receptors. Similar relations were measured during fictive locomotion despite the absence of muscular contraction and limb movement and the lack of change in metabolic rate. These findings provide experimental support for the central command hypothesis for the genesis of the respiratory hyperpnea and increased cardiovascular function that occur during exercise. We believe that the command signals emanate from the subthalamic locomotor area of the diencephalon.

Animals↗

PubMed1986

Resetting of mammalian respiratory rhythm: existence of a phase singularity.

The purpose of this study was to use topological methods of analysis to determine if a phase singularity exists for the neural respiratory oscillator. We studied resetting behavior of central respiratory rhythm, measured as phrenic nerve activity, by using brief stimulations of the superior laryngeal nerve in anesthetized paralyzed adult cats. The strength and timing of stimuli were varied, and the times of onset of subsequent breaths were measured. Two distinct types of phase resetting were identified: type 1 resetting for weak stimuli and type 0 resetting for strong stimuli. With stimuli of intermediate strength, we obtained a series of phase-resetting curves that defined a helicoid-resetting surface having a phase singularity near the transition between late expiration and early inspiration. In this domain resumption of breathing occurred at highly variable resetting times. The mammalian respiratory oscillator thus has qualitative characteristics of response to brief stimuli that are similar to those of other biological oscillators.

Animals↗

PubMed1986

Role of ventrolateral medulla in regulation of respiratory and cardiovascular systems.

It is now widely accepted that the ventrolateral aspect of the medulla oblongata (VLM) plays an important role in regulation of the respiratory and cardiovascular systems. The VLM has been implicated as being involved in a number of different physiological functions, including central chemoreception, integration of afferent inputs from certain sense organs to the respiratory and cardiovascular controllers, the source of excitatory input to preganglionic sympathetic neurons in the spinal cord, and location of synaptic relay between the higher brain defense areas and spinal cord sympathetic elements. In recent years there have been a number of important findings concerning both the anatomical substrate and neurophysiological characteristics of VLM neurons involved in regulation of the respiratory and cardiovascular systems. New anatomical findings show that neuronal networks located in the VLM send projections to and receive projections from brain stem nuclei that have traditionally been associated with respiratory and cardiovascular regulation. Nevertheless, there are still many important questions concerning the role of the VLM in control of these vital systems that have yet to be answered. For instance, are the same VLM neurons involved in control of both systems? Is the VLM the only site for central respiratory chemoreception? This review will endeavor to examine new findings and to reexamine some older findings concerning the VLM.

Animals↗