Apneic Response Research Articles

Functional subdivisions of the nucleus tractus solitarii of the rat as determined by circulatory and respiratory responses to electrical stimulation of the nucleus

We have recently identified two functional subdivisions of the nucleus tractus solitarii (NTS) in the cat: the pressor and apneustic (inspiratory) response zone, and the depressor and apneic (hypopneic) response zone. The presence of such functional subdivisions in the NTS of the rat was explored. The circulatory and respiratory responses to electrical stimulation of a small part of the NTS were surveyed in all regions of the NTS in rats anesthetized with urethane (500 mg/kg, i.p.) and chloralose (80 mg/kg, i.p.). A set of depressor, bradycardiac and apneic responses was elicited in the dorsomedial portions, whereas a pressor response with or without an apneic (hypopneic) response was elicited in the ventral and lateral portions. The presence of a difference in the functional subdivisions between spontaneously hypertensive rats (SHR) and normotensive rats (WKY) was also explored. The SHR group showed significantly larger pressor responses than the WKY group ( P < 0.001), despite its higher basal level of arterial blood pressure, but significantly fewer bradycardiac responses ( P < 0.001). This suggests the SHR group is more sensitive in terms of sympathetic vasomotor activity but less sensitive in parasympathetic cardioinhibitory activity. There was no significant difference in the distribution of the pressor and depressor response zones between the two strains.

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

Laryngeal chemoreflex: anatomic and physiologic study by use of the superior laryngeal nerve in the piglet.

The laryngeal chemoreflex (LCR) was investigated in 21 piglets (ages 6 to 80 days old) with the use of physiologic and histologic techniques. The central projection of the superior laryngeal nerve (SLN) was determined in 14 animals by use of horseradish peroxidase-wheat germ agglutinin. Ipsilateral labeling of the solitary tract nucleus was seen. The caudal extent of the labeling varied with age. Sensory labeling of the nucleus ambiguus was present bilaterally in three younger animals and unilaterally in older piglets. Bilateral labeling of the nucleus dorsomedialis was seen in all ages. Apneic and cardiovascular response to water stimulation of laryngeal mucosa and the laryngeal adductor reflex (LAR) were examined in 16 piglets. Blunting of the apneic and cardiovascular response was seen after sacrifice of a single SLN. Hypoxia did not significantly affect the LAR or apnea duration in animals with only one intact SLN. A contralateral LAR was found in younger animals. Relevance to the LCR is also discussed.

Study of possible transmitters in the solitary tract nucleus of the cat involved in the carotid sinus baro- and chemoreceptor reflex

By using a multibarrelled microelectrode, the possibility that putative transmitters may influence on the field potential evoked in the solitary tract nucleus by electrical stimulation of the carotid sinus nerve (the NTS response) was examined electrophysiologically in the cat. After iontophoretic application of a selective antagonist to the putative transmitter, it was determined whether or not the NTS response was influenced. Both substance P antagonist and naloxone altered the NTS response recorded in the depressor and apneic (or hypopneic) response zone as well as in the pressor and apneustic (or inspiratory) response zone throughout the rostral, intermediate and commissure regions, suggesting that substance P and opioid peptide may play the role of excitatory transmitters. Under the polarizing cathodal current which may activate inhibitory inputs to the site of the NTS response, bicuculline and prazosin strongly enhanced the NTS response recorded in the pressor and apneustic zone, while naloxone weakly enhanced the NTS response recorded in the depressor and apneic zone. These results suggest that γ-aminobutyric acid, α-adrenergic agonist and opioid peptide may have an inhibitory influence on the NTS response.

Projections to areas of the nucleus tractus solitarii related to circulatory and respiratory responses in cats

Using chloralose-anesthetized cats, afferent projections to the nucleus tractus solitarii (NTS) were studied in relation to circulatory and respiratory responses. Horseradish peroxidase (HRP) was injected into 3 distinct regions of the NTS: (1) the rostral regions from which electrical stimulation elicited pressor and apneustic responses; (2) the intermediate regions from which stimulation elicited depressor and apneic responses; (3) the commissure regions from which stimulation elicited depressor and hypopneic responses. HRP-labeled cells were sought throughout the medulla oblongata upward including the telencephalon. The results indicate that: (1) many neurons of the frontal cortex (sigmoid gyrus, anterior ectosylvian gyrus, anterior sylvian gyrus, and anterior suprasylvian gyrus) project bilaterally to the 3 regions, predominantly to the rostral regions; (2) a few neurons of the bed nucleus of the stria terminalis project almost ipsilaterally to the 3 regions; (3) a few neurons of the nucleus amygdalae centralis project almost ipsilaterally to the 3 regions; (4) many neurons of the paraventricular nucleus project bilaterally to the 3 regions, predominantly to the ipsilateral commissure regions; (5) a moderate number of neurons of the fastigial nucleus project contralaterally to the rostral regions. These findings suggest that there are some specific projections to each region of the NTS from various supramedullary nuclei, which may be involved in modulation of the cardiovascular and respiratory systems.

Behavioral control of breathing in the cat

Respiration depends upon brainstem neuronal circuits that produce the respiratory rhythm and relay it, via the ventrolateral columns, to motor neurons in the spinal cord. This brainstem system produces respiration automatically, i.e. without conscious effort, and is responsive to chemical and mechanical stimuli that signal imbalances in respiratory homeostatis. In addition to this automatic/metabolic respiratory system, there is a voluntary/behavioral system that controls the respiratory muscles during speaking, breath holding, and other voluntary respiratory acts. It has been proposed that this behavioral system involves corticofugal fibers that bypass the automatic system, course in the dorsolateral columns, and end at the level of the respiratory motor neurons. According to this scheme, the integration of behavioral control with automatic/metabolic control occurs at the level of the motor neurons and not within the automatic system. This proposed scheme has not been investigated experimentally. In the present study, we trained cats to control their respiration and recorded the activity of cells within the automatic system in the medulla during this behavioral control. We trained the animals to terminate inspiration and prolong expiration when a tone sounded. Microelectrode recordings from 40 medullary respiratory neurons showed that most cells, inspiratory and expiratory, became inactive during the behavioral apneic response. The exceptions were some expiratory cells that were activated during the task. These results suggest that the integration of behavioral influences occurs within the automatic system.

The functional subdivisions of the nucleus tractus solitarii of the cat in relation to the carotid sinus nerve reflex

The field potentials evoked by electrical stimulation of the afferent Aδ fibers of the ipsilateral carotid sinus nerve (CSN) were surveyed in all the regions of the nucleus tractus solitarii of the cat (NTS responses). Pressor and inspiratory responses, like the CSN chemoreceptor reflex, are elicited by electrical stimulation of the site of the NTS responses in the rostral regions, the lateral portions of the intermediate regions and the commissure regions. On the other hand, depressor and apneic responses, like the CSN baroreceptor reflex, are elicited by electrical stimulation of the site of the NTS responses in the medial portions of the intermediate regions and the dorsal portions of the commissure regions.

Somatostatin-induced apnea: Interaction with hypoxia and hypercapnea in the rat

The effects of hypoxia and hypercapnea in the production of somatostatin (SRIF)-induced apnea were studied during rebreathing experiments. Hypoxia and hypercapnea resulted in a shortening of the latency of SRIF-induced apnea. In order to exclude the effect of stimulation of central chemoreceptors by mock-CSF solution, control experiments using mock-CSF in combination with hypoxia and hypercapnea were done. No apnea could be produced by the mock-CSF in combination with hypoxia and hypercapnea. The shortening of apneic latency from 480 ± 8 s (S.E.M.) to 148 ± 30 s with the addition of a chemostimulus (hypoxia and hypercapnea) in SRIF-induced respiratory depression demonstrates that chemostimulation interacts with the centrally originating apnea to enhance its apneic response.

An efferent pathway mediating reflex tracheal dilation in awake dogs.

Lung inflation is known to produce reflex relaxation of tracheal smooth muscle (TSM) and dilation of the upper airway, but the specific efferent pathway involved has not been established. Therefore we examined TSM tone in four trained awake dogs by measuring pressure changes in the water-filled cuff of an endotracheal tube that was inserted into the lower cervical trachea through a permanent tracheostomy. Under control conditions, sustained lung inflation with 1 liter of air produced apnea (Hering-Breuer inflation reflex) and a decrease in cuff pressure (Pcuff) of 37.4 +/- 12.0 (mean +/- SD) cmH2O. beta-Adrenergic blockade with propranolol had no effect on either the apneic or TSM responses to lung inflation. Efferent parasympathetic blockade with atropine sulfate (1.2-2.4 mg) abolished TSM tone, which was then restored to control levels by a continuous intravenous infusion of serotonin (14-28 micrograms X kg-1 X min-1). Under these conditions, lung inflation still induced reflex apnea but no longer relaxed TSM tone (mean decrease in Pcuff, 2.7 +/- 1.4 cmH2O, P less than 0.001). The findings indicate that reflex tracheal dilation in response to lung inflation is mediated by an efferent cholinergic (parasympathetic) pathway.

Vagal feedback with expiratory threshold load under extracorporeal circulation.

In 11 anesthetized dogs placed under extracorporeal circulation, the vagal feedback was tested by electrical stimulation of the vagus nerves with cold block of their caudal part and by passive lung hyperinflation. The apneic response to such vagal stimulation progressively disappeared during expiratory threshold load breathing but then returned to control values some minutes after the load was removed. This suppression of the inhibitory response to stimulation of the vagus nerves was usually observed when vagal afferents were intact or blocked by cold. However, it was not observed whether no evoked activity continued in expiratory muscles after the cold block, or after suppression of all proprioceptive muscular afferents after transection of the spinal cord at C6 level. These results strongly suggest that enhancement of proprioceptive inputs to the respiratory centers counteracts the vagally mediated inspiratory "off-switch" mechanisms.

Physiological effects of controlled concussive brain trauma.

Utilizing a fluid percussion device, we measured the physiological effects of brain trauma in cats exposed to controlled levels of injury. Concussive brain injury at 3-4 atm of intensity led to profound elevations of the mean systemic arterial blood pressure from 128 +/- 26 to 229 +/- 33 mmHg, left ventricular end-diastolic pressure from 4 +/- 2 to 24 +/- 15 mmHg, and pulmonary wedge pressures (PWP) from 5 +/- 3 to 27 +/- 17 mmHg and a relatively moderate increase in intracranial pressure (ICP) from 6 +/- 3 to 38 +/- 31 mmHg (all P < 0.001). Pulmonary edema was evidenced by a significant increase in lung tissue wet-to-dry weight ratios to 3.74 +/- 0.81 as compared with a control group of 2.29 +/- 0.23 (P < 0.001). There was poor correlation between wet-to-dry weight ratios and PWP. Approximately 60% of all spontaneously breathing animals become permanently apneic within 6 min after injury, while the remaining 40% developed transient apnea. Arterial O2 or CO2 pressure alterations, in contrast to pretreatment with phentolamine did not affect the hemodynamic or edemogenic response to trauma. Phentolamine did not block the apneic response or increase in ICP. Comparative studies using intravenous levarterenol without trauma produced responses similar to trauma. Concussive brain injury of 3-4 atm results in pulmonary edema, apnea, sympathetically mediated peripheral vasoconstriction and left ventricular failure effect.

Ventilatory responses to CO2 and lung inflation in tonic versus phasic REM sleep

Ventilatory responses to CO2 and to lung inflation were compared in four dogs during tonic and phasic segments of rapid-eye-movement (REM) sleep. Phasic REM sleep (P-REM) was identified by the presence of bursts of rapid eye movements, visible muscle twitchings, and frequent phasic discharges in the nuchal electromyogram. These features were absent during tonic REM sleep (T-REM). During P-REM the response of minute volume of ventilation (VI) to progressive hypercapnia (0.58 +/- 0.19 (l/min)/Torr, mean +/- SE) was significantly less than in slow-wave sleep (SWS) (1.40 +/- 0.14; P less than 0.05). In contrast, during T-REM the response (1.48 +/- 0.19) was similar to that in SWS. Similarly, during P-REM the duration of apnea (5.9 +/- 1.5 s) elicited by sustained inflation of the lungs with 1.0 liter of air, was significantly shorter than in SWS (25.8 +/- 0.8); in contrast, during T-REM the duration of apnea (17.8 +/- 3.6) was similar to that in SWS. The results indicate that previously described decreases in VI responses to CO2 and apneic responses to lung inflation during P-REM, compared to SWS, are related to the phasic phenomena of REM sleep, rather than to the REM sleep state per se.

Cardiovascular and respiratory responses to right atrial injections of phenyl diguanide in pentobarbital-anesthetized newborn piglets.

The present series of experiments was designed to determine whether the piglet has mature cardiorespiratory responses to the administration of phenyl diguanide (PDG) similar to those reported in adult mammals. A total of 26 acutely instrumented piglets aged 2--23 days were lightly anesthetized with sodium pentobarbital. After control conditions were established, PDG was injected into the right atrium. Each animal was its own control for determination of presence and magnitude of aortic pressure, heart rate, respiratory rate and volume, and blood flow responses to test doses of PDG. A fall in blood pressure was observed in all animals within 2--4 sec after right atrial injection of PDG. Bradycardia occurred and a transient cardiac arrhythmia, consisting of 2nd and 3rd degree heart block, was observed in most animals; the latter has not been previously reported. Apnea followed by rapid shallow breathing was observed in most animals. This respiratory effect was more pronounced in the younger animals. After atropine, PDG elicited a monophasic rise in aortic pressure; the cardiac rhythm and rate changes were abolished. However, the apneic response was retained. Subsequent bilateral vagotomy abolished the hypotensive effect on PDG. Such results suggest the possibility that the piglet,s cardiorespiratory response to the administration of PDG may be evoked by stimulation of type J pulmonary receptors. These have been postulated to be responsible for the triad of responses of hypotension, bradycardia, and apnea seen in other species after PDG administration.

Laryngeal Chemosensitivity: A Possible Mechanism for Sudden Infant Death

In 32 anaesthetized piglets 1 to 42 days of age the distal trachea was cannulated and pressure changes were recorded. The proximal trachea was cannulated for introduction of test fluids into the laryngeal area. Arterial pressure, heart rate, and central venous pressure were continuously recorded. Arterial blood samples were obtained at intervals and analyzed for PO2, PCO2, pH, and hematocrit. Normal saline produced no, or brief, transitory alterations of the respiratory pattern and arterial pressure. In contrast, instillation of distilled water produced apnea in 29 of 30 piglets. In 20 the apnea was sustained. Eleven died within approximately 50 minutes of asphyxia. An additional nine were expected to die with continuing apnea (PO2, 10 to 15 mm Hg; PCO2 greater than 100 mm Hg; pH smaller than 6.8) but the sequence was interrupted by replacement of water with saline. Twenty-three of 29 piglets showed an apneic response to cow's milk similar to that seen with distilled water. Seven died of asphyxia and an additional three showed sustained respiratory inhibition until milk was replaced with saline. The responses were completely abolished by superior laryngeal nerve (SLN) sectioning. Electrical stimulation of the SLN produced sustained apnea in seven of eight piglets tested. Studies in two 3-day-old lambs showed similar discrimination but only transitory apnea with water or cow's milk. Both died during SLN stimulation. Two ewes showed insignificant responses. These findings suggest a lethal reflex mechanism with implications for the SIDS problem.

Letters to the Editor

Dr. Steinschneider commented as follows: By pointing out a potential value for obtaining electrocardiographic recordings, Dr. Bachman directs our attention to the more general need for describing and determining those variables influencing the pattern (and magnitude) of physiological changes occurring in conjunction with or as a consequence of periods of prolonged sleep apnea. This concern is consistent with the conclusion reached by Daily et al.1 that, ". . . cardiocirculatory adjustments are an integral part of the apneic response . . ." (p. 516) and the hypothesis that prolonged sleep apnea is part of the physiologic process resulting in SIDS.

Angiographic demonstration of total renal shutdown during apneic “diving” in the rabbit

1. 1. Serial angiograms were taken following intra-aortic injections of contrast medium in free breathing animals and during apnea. Accompanying the characteristic bradycardia, a marked differential vasoconstriction occurs in the splanchnic bed during the “dive” with an apparent total cessation of blood flow to the kidneys and an increased perfusion of certain areas such as the spinal cord and brain. 2. 2. This readily elicited reflex may serve as a useful model in examining related vasoconstrictor influences pertaining to shock and the actions of certain vasopressor agents. 3. 3. The apneic response in the rabbit closely resembles the well-known diving reflex in aquatic birds and mammals.

Sensitivity to inflation of the respiratory system in the chicken

Experiments were conducted on two breeds of chickens, as well as on rabbits and dogs, to quantitate the reflex respiratory alterations induced by inflation of the ventilatory systems. For all three species the length of apnea produced by inflation with air was related logarithmically to inflation pressure. Carbon dioxide (5 to 8 %) added to the inflating gas did not influence the apneic response in the mammals; however, in chickens inflation with this gas did not cause apnea but produced only a slight decrease in respiratory rate. Results of these experiments failed to demonstrate the presence of stretch receptors in the respiratory system of chickens. However, receptors sensitive to intrapulmonary CO 2 concentrations appear to provide a strong peripheral influence on the control of respiration in these animals.

Pulmonary Circulation Time in the Chicken ,

INTRODUCTIONSUDDEN removal of carbon dioxide from the gas stream of the unidirectionally, artificially ventilated chicken results in the initiation of apnea in approximately 0.5 seconds (Peterson and Fedde, 1968). It was considered possible that blood, equilibrated with the low air capillary PCO2, could be conveyed from the pulmonary capillaries to the aortic and carotid bodies in this short time and that these receptors might be involved in the apneic response. The purpose of this study was to obtain an estimate of the minimal circulation time of blood from the pulmonary artery to the left ventricle in an attempt to determine if the systemic arterial chemoreceptors could be involved in the rapid respiratory response to airway CO2 removal.METHODSFive adult, male Single Comb White Leghorn chickens, which had fasted for 12 hours, were used for our experiments. Each bird was restrained in dorsal recumbency and surgically anesthetized (approximately 30…

THE NERVOUS CONTROL OF RESPIRATION IN KITTENS

ArticleTHE NERVOUS CONTROL OF RESPIRATION IN KITTENSHelen C. Coombs, and F. H. PikeHelen C. CoombsFrom the Department of Physiology, New York Homeopathic Medical College, and Columbia University, and F. H. PikeFrom the Department of Physiology, New York Homeopathic Medical College, and Columbia UniversityPublished Online:01 Dec 1930https://doi.org/10.1152/ajplegacy.1930.95.3.681MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPostnatal development of right atrial injection of capsaicin-induced apneic response in ratsRurong Wang, and Fadi Xu1 July 2006 | Journal of Applied Physiology, Vol. 101, No. 1Hypoxemia and low Crs in vagally denervated lambs result from reduced lung volume and not pulmonary edemaSalim Lalani, John E. Remmers, Yolanda MacKinnon, Gordon T. Ford, and Shabih U. Hasan1 August 2002 | Journal of Applied Physiology, Vol. 93, No. 2Effects of vagal denervation on cardiorespiratory and behavioral responses in the newborn lambSalim Lalani, John E. Remmers, Francis H. Green, Ashfaq Bukhari, Gordon T. Ford, and Shabih U. Hasan1 November 2001 | Journal of Applied Physiology, Vol. 91, No. 5Pulmonary vagal innervation is required to establish adequate alveolar ventilation in the newborn lambKevin A. Wong, Ather Bano, Anita Rigaux, Bing Wang, Baikhunth Bharadwaj, Samuel Schürch, Francis Green, John E. Remmers, and Shabih U. Hasan1 September 1998 | Journal of Applied Physiology, Vol. 85, No. 3 More from this issue > Volume 95Issue 3December 1930Pages 681-693 Copyright & PermissionsCopyright © 1930 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1930.95.3.681History Received 20 September 1930 Published online 1 December 1930 Published in print 1 December 1930 Metrics