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Biomedical subjects

F L Eldridge

Publications and source records attributed to F L Eldridge.

At least 55 records · Page 3Linked to original sources
PubMed1984

Oscillations of medullary extracellular fluid pH caused by breathing.

The purpose of this study was to determine if respiratory oscillations of arterial PCO2 are transmitted to the medullary ECF. Anesthetized, paralyzed cats whose vagi and carotid sinus nerves had been cut were studied. A flat surfaced pH electrode (2 mm in diameter) and a specially built differential amplifier were used to measure pH on the ventral surface of the medulla. Elimination of noise and high sensitivity were obtained by integrating the output from the pH amplifier with a digital voltmeter . We measured ECF pH oscillations that had the same period as the ventilator. The amplitude of the oscillations was about 0.006 unit when the ventilator was slow (less than 10/min). The amplitude decreased progressively as the rate was increased and oscillations were usually undetectable at rates above 25/min. Experiments were performed that ruled out mechanical artifact and ventilator-related fluctuations in arterial pressure as being causal. We conclude that oscillations of alveolar CO2 are transmitted to the brain by the circulation and result in oscillations of ECF pH.

Animals↗
PubMed1984

Prolonged inhibition of respiration following acute hypoxia in glomectomized cats.

Respiratory responses to several minutes exposure to hypoxia (PaO2 less than 30 torr) were determined in anesthetized, paralyzed, vagotomized and glomectomized cats whose end-tidal PCO2 and body temperature were kept constant. Respiratory activity was quantified from phrenic nerve activity. Animals breathed 100% O2 during the control period. The study reaffirmed that in glomectomized animals hypoxia causes depression of respiratory activity. The new finding was that phrenic activity remained significantly depressed below the original control level for more than one hr after return to the hyperoxic state. Medullary ECF pH was measured in 3 cats. There was an acid shift of pH during hypoxia that persisted for more than one hour after return to hyperoxic state. We pretreated another group (n = 5) of animals with theophylline, a specific antagonist of the inhibitory neurotransmitter adenosine. Hypoxia still caused depression of respiratory activity, but it was less severe than in untreated animals. Upon return to the hyperoxic state, respiratory activity returned to the original control level within 10 min. We conclude that the long-lasting depression of respiration following hypoxia is mediated by adenosine. Furthermore, adenosine appears to be partially responsible for the acute depression of respiration during the hypoxic exposure.

Acute Disease↗
PubMed1984

Brain, blood and rectal temperature during whole body cooling.

To determine if rectal temperature is an adequate index of brain temperature during changing thermal conditions, we measured rectal, cerebral cortical, and carotid arterial blood temperatures simultaneously during whole body cooling in adult cats. The mean steady state rectal, brain and carotid arterial temperatures at the onset of cooling were: 39.2 +/- 0.2, 38.5 +/- 0.2, and 38.3 +/- 0.3 degrees C, respectively. Rectal temperature decreased faster than both brain and arterial blood, while only a small temperature difference was observed between brain and arterial blood, brain always exceeding blood. Rectal temperature cannot be considered an adequate index of brain temperature. Carotid arterial temperature is a better estimate of brain temperature.

Animals↗
PubMed1984

Respiratory effects of carbon dioxide-induced changes of medullary extracellular fluid pH in cats.

Acute and steady-state responses to hypercapnia of respiratory output, measured as integrated phrenic nerve activity, and medullary extracellular fluid (e.c.f.) pH, measured directly, were determined in paralysed, vagotomized and glomectomized cats. Medullary e.c.f. pH responds within seconds to an acute change of alveolar and arterial PCO2. The respiratory response closely and inversely matches the e.c.f. pH change, but not the cerebrospinal fluid pH change. The medullary e.c.f. pH change following a rapid step-change in end-tidal PCO2 requires at least 5 min for a new steady state to be achieved. Steady-state studies in twenty-six cats show: (a) that the respiratory response to progressive hypercapnic stimulation of the central chemoreceptors is curvilinear (Eldridge, Gill-Kumar & Millhorn, 1981), (b) that the relationship between increasing end-tidal PCO2 and medullary hydrogen ion concentration [(H+]) or changes of pH is linear (r = 0.995); a doubling of PCO2 causes 0.260 units pH change, (c) there is a curvilinear relationship between e.c.f. [H+] and the respiratory response that is the same as that found with CO2. We conclude that medullary e.c.f. pH measured by means of a surface electrode accurately reflects the CO2-induced [H+] stimulus to respiration. The decreasing respiratory responses to identical changes of central chemoreceptor input are due to progressive neuronal saturation of a central pathway between the chemoreceptors and the respiratory controller.

Animals↗
PubMed1984

Respiratory responses to noxious and nonnoxious heating of skin in cats.

Respiratory responses to increased skin temperatures were recorded in anesthetized cerebrate and in unanesthetized decerebrate cats. All were vagotomized, glomectomized, and paralyzed. Core body temperature and end-tidal Pco2 were kept constant with servoncontrollers. Stimulation of cutaneous nociceptors by heating the skin to 46 degrees C caused respiration to increase in both cerebrate and decerebrate cats. An even larger facilitation of respiration occurred when the skin temperature was elevated to 51 degrees C. However, respiration did not increase in either group of cats when the skin was heated to 41 degrees C to activate cutaneous warm receptors. The phenomenon of sensitization of nociceptors was observed. Spinal transection prevented all the respiratory responses to cutaneous heating. We conclude that noxious, but not nonnoxious, increases in skin temperature cause increases in respiratory output.

Animals↗
PubMed1983

Centrally and peripherally administered 5-HTP have opposite effects on respiration.

5-Hydroxytryptophan (5-HTP) caused a prolonged increase of respiratory (phrenic nerve) activity when given into the third ventricle of paralyzed, vagotomized and glomectomized cats. In contrast, intravenous 5-HTP always led to a prolonged inhibition. These findings must be due to different modes of action of the same drug given by different routes and illustrates that caution must be used in interpreting experimental results following administration of exogenous agents.

5-Hydroxytryptophan↗
PubMed1983

Central neural stimulation of respiration by sodium salicylate.

Phrenic nerve responses to intravenous administration of sodium salicylate were measured in anesthetized, paralyzed cats whose vagi and carotid sinus nerves had been cut. Three groups of animals were studied. One consisted of animals with intact central nervous systems. The other two were identical except that the spinal cords had been transected at either T4-T5 or C7-T1. Salicylate led to a significant increase in respiration and whole body metabolism in all three groups. Transection of the spinal cord had no effect on the magnitude of the respiratory response to salicylate. We also studied another group of animals in which salicylate was injected directly into the third cerebral ventricle. This led to a significant increase in respiration without an increase in whole body metabolism. We conclude that salicylate stimulates respiration by a mechanism other than one related to its ability to increase whole body metabolism and that this mechanism is located within the central nervous system.

Animals↗
PubMed1983

Inhibition of breathing after stimulation of muscle is mediated by endogenous opiates and GABA.

Stimulation of receptors in hindlimb muscles activates a supraspinal mechanism which causes a prolonged, post-stimulatory depression of breathing (Waldrop, T.G., F.L. Eldridge and D.E. Millhorn, 1982, Respir. Physiol. 50: 239-254). In the present study phrenic nerve responses to stimulation of hindlimb muscles were studied in anesthetized, paralyzed cats whose vagi and carotid sinus nerves had been cut. Body temperature and end-tidal PCO2 were kept constant with servocontrollers. The post-stimulatory depression of breathing was greatly attenuated in cats pretreated with an opiate antagonist (naloxone) and did not occur in animals pretreated with a GABA antagonist (bicuculline). The response was not blocked by prior administration of either a serotonin antagonist (methysergide) or a dopamine and norepinephrine antagonist (alpha-methyltyrosine). We conclude that endogenous opiates and possibly GABA, but not serotonin, dopamine or norepinephrine, are involved in the neural mechanism responsible for the prolonged depression of breathing.

Animals↗
PubMed1983

Mechanism of respiratory effects of methylxanthines.

Neural respiratory responses to theophylline, aminophylline and ethylenediamine were determined in paralyzed, vagotomized and glomectomized cats whose end-tidal PCO2 and brain temperature were kept constant. Intravenous theophylline and aminophylline similarly stimulated respiration, but ethylenediamine had no effect. The following did not cause the response: muscular and mechanical factors, carotid body and vagal reflexes, spinally mediated mechanisms arising below C7, changes of arterial PCO2 or medullary ECF pH, changes of whole body metabolic rate or release of substances from the adrenal glands. Absence of suprapontine brain did not prevent the response. Pretreatment with a serotonin antagonist did not affect the response but two different dopamine antagonists caused its attenuation. When administered into the third ventricle, theophylline did not stimulate respiration, but both aminophylline and ethylenediamine, due to the latter's ability to mimic the inhibitory effects on neurons of gamma-aminobutyric acid (GABA), caused significant depression of respiration. We conclude that the neural respiratory response to systemically administered theophylline is mediated at the level of the brainstem, and somehow involves the action of the neurochemical dopamine. The failure of cerebroventricularly administered theophylline to stimulate respiration must be related to its inability to reach the appropriate neurons from the cerebrospinal fluid.

Aminophylline↗
PubMed1982

Prolonged post-stimulus inhibition of breathing following stimulation of afferents from muscle.

Respiratory responses, measured from phrenic nerve activity, to stimulation of limb muscles or their afferent nerves were studied in anesthetized cats with intact brains, after cerebellectomy or decortication, and in unanesthetized decerebrate animals. All were vagotomized, glomectomized and paralyzed. Body temperature and end-tidal PCO2 were kept constant with servocontrollers. Nerve or muscle stimulation in animals with intact brains caused an increase in respiration which was followed by a respiratory afterdischarge, both of which have been described previously. In addition, stimulation of either muscle or nerve in animals with intact brains caused a post-stimulation depression of respiration that persisted for up to an hour. Decerebrated animals or those with spinal cord transection at cervical, thoracic or lumbar levels did not develop the response. In decorticated or decerebellated animals, the magnitude of the prolonged inhibition was markedly decreased. We conclude that: (1) stimulation of limb muscles or their afferent nerves activates a central neural mechanism which causes a prolonged depression of respiration; (2) the afferent input involved in this response is transmitted to the brain via spinal cord pathways; and (3) the cerebellum and suprapontine brain are required for full development of the post-stimulation inhibition.

Animals↗
PubMed1982

Effects of medullary area I(s) cooling on respiratory response to chemoreceptor inputs.

The effect on respiration, as measured by phrenic nerve activity, of bilateral graded cooling of the intermediate, or I(s), areas of the ventral medulla was determined in anesthetized, vagotomized, glomectomized and paralyzed cats. In addition the effect of cooling the I(s) areas on the responses to central and peripheral chemoreceptor afferent test stimuli were studied. When end-tidal PCO2 was kept constant, graded cooling of the I(s) areas led to graded reductions of phrenic activity and arterial pressure. Furthermore, the respiratory response to test stimuli (carotid sinus nerve or CO2) was decreased progressively during graded cooling of the I(s) areas from 40 degrees C to 20 degrees C. We conclude that area I(s) is part of a common pathway for afferent input from both the central and peripheral chemoreceptors and that it is involved in the initial integration of both inputs.

Animals↗
PubMed1982

Effects of medullary area I cooling on respiratory response to muscle stimulation.

The respiratory response to afferent input from both peripheral and central chemoreceptors can be decreased progressively by bilateral graded cooling of the intermediate, or I(s), areas of the ventral medulla (Millhorn et al., 1982). The present study was undertaken to determine if the phrenic nerve response to calf muscle afferent test stimulation is also affected by graded cooling of the I(s) areas. Anesthetized, paralyzed cats whose vagi and carotid sinus nerves had been cut were studied. Unlike the response to chemoreceptor input, the response to calf muscle input was not affected by moderate (40 degrees C to 20 degrees C) cooling of the I(s) areas. Thus, we conclude that input from both chemoreceptors travels to the respiratory controller via a common pathway that includes the I(s) areas, whereas input from peripheral muscle reaches the controller via an independent pathway that does not include the I(s) areas.

Animals↗
PubMed1982

Input-output relationships of the central respiratory controller during peripheral muscle stimulation in cats.

1. Inspiratory output responses, measured as integrated phrenic activity, to hypercapnia, to carotid sinus nerve stimulation, to unilateral and bilateral stimulation of calf muscles and to combinations of these stimuli were determined in paralysed, vagotomized and glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. 2. Confirming an earlier report (Eldridge, Gill-Kumar & Millhorn, 1981), the inspiratory response to progressive hypercapnic stimulation of the central chemoreceptors was not linear, and the responses to a constant carotid sinus nerve test stimulus were progressively decreased in magnitude as the pre-stimulus level of respiratory activity was increased by hypercapnia. 3. In contrast, the response to a test stimulus from calf muscles remained the same at all pre-stimulus levels of respiratory activity, whether conditioned by hypercapnia or by carotid sinus nerve stimulation. 4. Unlike the findings with chemoreceptor inputs, the combining of stimuli from right and left muscles exhibited an algebraically additive effect on output. 5. We suggested before that the decreasing responses to identical chemoreceptor inputs were due to progressive neuronal saturation of a common central pathway between these inputs and the respiratory controller. The absence of such behaviour with muscular afferent input indicates that this input does not travel to the respiratory controller by the same pathway as that common to the chemoreceptors.

Action Potentials↗
PubMed1982

Effects of salicylate and 2,4-dinitrophenol on respiration and metabolism.

The respiratory and metabolic responses to intravenous administration of sodium salicylate (240 mg/kg0.75) and 2,4-dinitrophenol (5.7 mg/kg0.75), uncouplers of oxidative phosphorylation, were studied in anesthetized, paralyzed, vagotomized, and glomectomized cats. During the initial 10 min after administration of salicylate, metabolic rate (VCO2) increased 70% and did not increase further during the experiment. Respiration, on the other hand, increased progressively at the same rate over the entire 60-min course of the experiment. The total increase in respiration was greater than 300%. Thus neither the time course nor the magnitude of the metabolic and respiratory responses were related. Similar findings were also obtained following administration of 2,4-dinitrophenol. We conclude that these agents stimulate respiration by a mechanism other than one related to the ability to uncouple oxidative phosphorylation and cause an increase in whole-body metabolism.

2,4-Dinitrophenol↗
PubMed1981

Exercise hyperpnea and locomotion: parallel activation from the hypothalamus.

Unanesthetized decorticate cats walked or ran normally on a treadmill either spontaneously or during electrical stimulation of the subthalamic "locomotor" region. The respiratory response usually preceded the locomotor response and increased in proportion to locomotor activity despite control or ablation of respiratory feedback mechanisms. Respiration increased similarly in paralyzed animals during fictive locomotion despite the absence of muscular contraction or movement. Hypothalamic command signals are thus primarily responsible for the proportional driving of locomotion and respiration during exercise.

Animals↗
PubMed1981

Spinal inhibition of phrenic motoneurones by stimulation of afferents from peripheral muscles.

1. Phrenic nerve responses to stimulation of calf muscle receptors or their afferents were studied in two groups of cats. One consisted of paralysed, vagotomized and functionally glomectomized animals with intact central nervous systems. The other included paralysed high (C1) spinal animals whose phrenic nerve activity was either spontaneously tonic or phasic, or evoked by activation of the intercostal-to-phrenic reflex. In both groups, end-tidal PCO2 was maintained at a constant level by means of a servo-controller. 2. Physical stimulation of calf muscles in animals with intact central respiratory controller and a generally facilitatory effect on frequency, with appropriate changes of both inspiratory and expiratory durations, and on peak magnitude of phrenic (neural tidal) activity. However, for the first few sec after onset of the stimulus, neural tidal activity was inhibited. 3. Physical stimulation of calf muscles or electrical stimulation of the tibial nerve in high spinal animals uniformly caused inhibition of spontaneous phrenic activity and that evoked by facilitatory conditioning stimuli. The degree of inhibition gradually decreased as muscle stimulation continued. Following offset of muscle stimulation, post-stimulus augmentation of phrenic activity occurred, with subsequent gradual return to control level over a period of 20-25 sec. 4. We conclude that stimulation of muscle afferents in the leg has a predominantly facilitatory respiratory effect when acting through brain stem controller mechanisms, but also has a purely inhibitory effect on phrenic motoneurones when acting via spinal mechanisms. 5. In addition, the findings are consistent with (1) progressive accommodation of phrenic motoneurones during continued inhibitory input, and (2) with a large and prolonged post-inhibitory rebound of excitability.

Animals↗
PubMed1981

Input-output relationships of central neural circuits involved in respiration in cats.

1. Inspiratory output responses, measured as integrated phrenic activity, to hypercapnia, to unilateral and bilateral carotid sinus nerve stimulation and to combinations of these stimuli were determined in paralysed, vagotomized and glomectomized cats whose end-tidal P(CO2) was kept constant by means of a servo-controlled ventilator. In addition, the effect on these responses of the mechanism that causes the respiratory after-discharge was determined.2. Above the threshold for rhythmic activity, the inspiratory response to hypercapnic stimulation of the central chemoreceptor was curvilinear, showing progressively smaller increments of output for equal increments of P(CO2) as the latter became higher.3. The combining of stimuli from right and left carotid sinus nerves failed to show an algebraically additive effect; the response was approximately 70% of that predicted from a summing of the separate stimuli given alone.4. The response to a constant carotid sinus nerve test stimulus was progressively decreased in magnitude as the pre-stimulus level of respiratory activity was increased by conditioning stimulation of the central chemoreceptors by hypercapnia, by stimulation of the opposite carotid sinus nerve or by the mechanism that generates an after-discharge.5. From a descriptive standpoint, our findings show that there is a negative or hypoadditive interaction between the peripheral and central inputs at the level of the central respiratory controller. However, we present evidence that, rather than being a specific interaction between peripheral and central inputs, the response is due to the properties of a neural component of the central pathway. This component is common to both inputs and develops progressive saturation of its neural elements as its activity increases.6. In addition, the neural mechanism which generates a respiratory after-discharge appears to saturate completely at a lower level of inspiratory activity than that at which the common pathway develops complete saturation. This finding supports the idea that this mechanism represents an independent input to the respiratory controller.7. Because the described a-linear response characteristics of the central respiratory controller are due to its inherent neuronal properties rather than to specific interactions between inputs, we suggest that studies of such ;interactions' must be interpreted with this consideration in mind.

Animals↗