Lung Stretch Receptors Research Articles

Synaptic action of R β neurons on phrenic motoneurons studied with spike-triggered averaging

The functional role of dorsal medullary inspiratory neurons with excitatory input from lung stretch receptors (R beta neurons) is a matter of controversy. The present study, performed on chloralose-anesthetized and paralyzed cats, ventilated mainly with a phrenic-controlled servorespirator, deals with the spinal projection of these neurons, a property which suggests their involvement in the efferent part of the medullary respiratory complex. Out of 37 inspiratory neurons which could be excited antidromically following microstimulation within the contralateral C6 phrenic nucleus (latency 2.0 ms +/- 0.4, S.D.), 17 were classified by the 'no-inflation' test as R beta. Intracellular recording of synaptic potentials from phrenic motoneurons using the 'spike-triggered averaging' technique were made. In 10 phrenic motoneurons, the averaging revealed individual EPSPs (peak amplitude 150 +/- 110 microV, rise time 0.5 +/- 0.2 ms) time-locked to action potentials of 5 out of 7 R beta neurons tested. Cross-correlation of the R beta neurons firing with the activity of C5 and C6 phrenic rootlets indicated a divergence of excitatory action within the phrenic nucleus. For comparison, in 3 phrenic motoneurons individual EPSPs were recorded when the activity of 3 R alpha cells was used to trigger the averaging. It is concluded that at least some R beta neurons, similarly to R alpha neurons, project to the contralateral phrenic nucleus and can make monosynaptic excitatory connections with phrenic motoneurons. The finding that individual EPSPs were similar when averaging was triggered by the activity of either R beta or R alpha neurons provides new evidence for our earlier hypothesis that bulbospinal inspiratory neurons of the solitary tract nucleus may be subdivided into two categories only on a quantitative basis.

Reticular formation of the lower brainstem. A common system for cardiorespiratory and somatomotor functions: discharge patterns of neighboring neurons influenced by cardiovascular and respiratory afferents

Experiments were done in dogs with chloralose-urethane anesthesia. Long-lasting extracellular recordings were made from the medial parts of the reticular formation of the lower brainstem for up to 250 min. The study is based on reactions of 103 neurons. The activities of 2 or 3 neighbouring neurons recorded under identical conditions with one electrode or of neurons recorded with two electrodes at the same time could be changed regularly and synchronously by experimental changes of hemodynamic or ventilatory parameters. Action potentials were separated by amplitude discrimination. Rhythmic pulsatile modulations were proved to be present in 78% of all neurons by post-event-time histograms triggered by the R-wave of the ECG. In the 96 neurons tested 86% changed their activity when arterial pressure was raised by inflating a balloon in the abdominal aorta (79% decreased and 7% increased their activity). In post-event-time histograms triggered by the start of inspiration, 83% of the neurons showed modulations of their activity with respiratory rhythm. Experimental lung inflation decreased the activity in 75% of the tested neurons, while experimental lung deflation activated 47% of the tested neurons. Stimulation of arterial chemoreceptors activated 77% of the tested neurons. It was thus demonstrated that receptors in the cardiovascular and respiratory systems exert an influence on nearly all neurons from which recordings were made in that part of the reticular formation. Arterial baroreceptors and lung stretch receptors revealed a generalized depressing effect on the neuronal activity while chemoreceptors exert a generalized augmenting effect. At different times of recording these neurons did not always react to the same extent to comparable stimulations of afferents.

Onset of inspiration in rabbit during artificial ventilation.

1. We have investigated whether pulmonary stretch receptors are the only lung receptors determining the time of onset of inspiratory efforts in anaesthetized, paralysed rabbits. 2. New Zealand White rabbits were anaesthetized, paralysed and ventilated by intermittent positive pressure with a pattern that closely followed spontaneous breathing. Inspiratory efforts were recorded as bursts of activity in a root of the phrenic nerve. Lung stretch receptors were blocked with SO2 in air. Abolition of the Breuer-Hering reflex was used as an index of stretch receptor block. 3. With stretch receptors functioning phrenic discharge invariably occurred during the deflation phase of ventilation. With stretch receptors blocked phrenic discharge occurred with no set relation to ventilation at spontaneous resting tidal volume but was locked to inflation and deflation phases of lung volume at 30% higher tidal volumes. 4. Bilateral vagotomy produced a pattern of phrenic discharge identical with that seen with stretch receptor block and low ventilating volumes. 5. Thus we have demonstrated a vagally mediated inspiratory initiating effect; it probably originates from rapidly adapting lung irritant receptors.

Response of the dorsomedial respiratory neurons of cats to changes in lung volume

The extracellular activity of single respiratory neurons in the region of the nucleus tractus solitarius was monitored in anesthetized cats. The responses to a series of tests manipulating lung volume were assessed by measuring the changes in modal firing frequency and in the average number of spikes per breath, between 10 pairs of test and control breaths. The results showed that the neurons could be classified into two types, R α and R β. For test maneuvers in which lung volume stayed within the eupneic range the results showed that R β neurons received a direct excitation varying with increasing lung volume. The R α neurons received an indirect inhibition in the form of shortened burst durations varying with increasing lung volume. These effects were thought to be mediated by lung stretch receptors. For test maneuvers in which hyperinflation of the lungs occurred, so that a gasp response was observed, the results showed that both R α and R β neurons received a direct excitation. The gasp response to hyperinflation was thought to be mediated by lung irritant receptors. It was concluded that R β neurons are directly excited by lung stretch receptors and irritant receptors. R α neurons are directly excited by lung irritant receptors but only indirectly inhibited by lung stretch receptors. The observations are in disagreement with the hypothesis of a direct inhibition of R α neurons mediated by R β neurons, and suggest that the relations between these two types of respiratory neurons are more complex.

Assessment of the central chemosensitivity in man under transient or progressive hypercapnia.

In healthy man, the central chemosensitivity to CO2 was studied after depression of the arterial chemoreflex drive by inhalation of pure oxygen. The effectiveness of the functional decrease of arterial chemoreceptor function was assessed by the delayed hyperventilation which followed transient inhalation of hypercapnic gas mixtures for 3 or 5 breaths in hyperoxic conditions. In such a case the first significant increase in tidal volume (VT) occurred 13.9 +/- 3.2 (SE) sec later than the early change in this variable measured in normoxic conditions. The stimulus strength was estimated by the change in CO2 partial pressure in end-tidal alveolar gas (delta PETCO2). The central chemosensitivity (SCO2), defined as the ratio between change in ventilation (delta V) and delta PETCO2, was assessed either by transient inhalation of gas mixtures containing 5 to 8% CO2 in pure O2 ("varying transients") or by progressive hypercapnia (rebreathing in pure O2). In both cases, the first significant change in ventilation was due to an increase in VT, but, for a given delta PETCO2, VT changes were higher during rebreathing than after transient hypercapnia; (2) The respiratory frequency (fR) was progressively enhanced during rebreathing (shortening of expiratory duration in all cases and of inspiratory time in some subjects) but the ventilatory rhythm diminished after transient stimulation as soon as delta PETCO2 reached one kPa, and this was due to an increase in inspiratory duration; (3) The associated changes in VT and fR during rebreathing could explain that SCO2 values given by this method were 5.2 times greater than after transient hypercapnia ("varying tests"). The differences are discussed in terms of, (1) isolated changes in arterial PCO2 or associated decrease in pH of the cerebrospinal fluid; (2) changes in brain blood flow, and (3) stimulation of lung stretch receptors by the important increase in VT during rebreathing.

Studies on the synaptic interconnection between bulbar respiratory neurones of cats

In cats anaesthetized with pentobarbital, medullary respiratory neurones of both dorsal and ventral populations were recorded intracellularly with 1 mol.l-1 KCl-electrodes. The neurones were classified according to the projection of their axons to the spinal cord (bulbospinal neurones) or to the vagal nerves (vagal neurones). Those neurones which could not be activated antidromically (NAA-neurones) by either procedure were subdivided into (inspiratory) R beta-neurones, which were monosynaptically excited by lung stretch receptor afferents, and into inspiratory and expiratory NAA-neurones, which did not receive a direct synaptic input, from these afferents. All types of neurone investigated revealed postsynaptic activity during both inspiration and expiration. The periods when synaptic activity was minimal were the periods of transition between respiratory phases. The input resistance of most respiratory neurones varied in parallel with the respiratory cycle. A drastic fall of the input resistance during expiration was observed in R beta-neurones and in some inspiratory vagal neurones. This was not seen in inspiratory bulbospinal neurones. In stable intracellular recordings, periodic postsynaptic inhibition was demonstrated in 52 of 53 respiratory neurones by IPSP reversal following chloride injection. Maximal membrane potential then was generally reached during one of the periods of respiratory phase transition. Reasons for the failure of others to demonstrate these IPSPs are presented and discrepancies between other findings and these are discussed. It is concluded that reciprocal inhibition between bulbar respiratory neurones does exist and is a general phenomenon. It is argued that reciprocal inhibition is the fundamental mechanism underlying respiratory gating of afferent inputs. The probable existence of recurrent inhibition is inferred from the changes in the pattern of membrane depolarization during the active period of neurones.

Short-latency ventilatory responses to sudden withdrawal of hypoxia at normal and raised body temperature in man.

Approximately isopnoeic conditions (VE=40 l/min) were achieved by the inhalation of asphyxial gas mixtures (PA,O2 60 torr, PA,CO2 40-45 torr) in normothermia after a rise in rectal temperature of 1.6 degrees C had been induced by a heated flying suit. Arterial chemoreceptor drive was transiently reduced by either isocapnic removal of hypoxia (type (1) tests: two breaths of CO2 in O2) or simultaneous withdrawal of both hypercapnia and hypoxia (type (2) tests: two breaths of O2). 8-13 tests of each type were performed at both temperature conditions in 6 expts. on 4 healthy human subjects. Expired volume, total breath duration and inspiratory time were recorded, and minute ventilation and expiratory time subsequently computed breath by breath. In hyperthermia the steady-state ventilation of 40 l/min (at a relatively higher respiratory frequency and a correspondingly lower tidal volume) was achieved at a PA,CO2 which was 5 torr lower than in normothermia. Ventilation decreased significantly in all tests. Tested with a 3-way analysis of variance significant differences between the ventilatory responses at the two temperature conditions, and between the two test types were found. The rate of change of ventilation was greater in hyperthermia than in normothermia, and also greater in type (2) tests than in type (1) tests. Since isopnoeic conditions existed prior to the tests, this implies that the arterial chemoreceptor contribution to the total ventilatory drive is increased in hyperthermia. In type (2) tests a significant lengthening of expiratory time was observed in the first test breath. This finding confirms the effect in man of changes in airway PCO2 on lung stretch receptor discharge.

Changes in the Breuer-Hering reflexes following rostral pontine lesion

The lung stretch reflex characteristics of unanesthetized decerebrate cats were determined using servo-controlled lung volume changes before and after bilateral lesion of the dorsolateral rostral pons in the region of nucleus parabrachialis medialis (NPBM). During the inspiratory phase the time-dependent threshold curve for inspiratory inhibition by lung inflation was shifted to larger volumes after lesion with no change in the constant describing its rate of decay. During the expiratory phase the gain of the inflation reflex was found to be increased by lesion, but otherwise to remain qualitatively the same. Deflations during the expiratory phase revealed a prolonged central inhibitory state with reduced rate of decay late in expiration. It is concluded that with intact vagi structures in the region of NPBM constitute but one of at least three sources of inspiratory inhibition, feedback derived from peripheral lung stretch receptors and from caudal pontine or medullary neurons also being involved. It is also concluded that the structures in the vicinity of NPBM affect the switching mechanisms differently during the two phases of the cycle: During inspiration they contribute a tonic threshold lowering input to the inspiratory 'offswitch'; whereas, during expiration they provide inspiratory-facilitatory influences late in the phase.

The effects of irritation at various levels of the airway upon tracheal mucus secretion in the cat.

1. Sulphated glycoprotein output from the trachea, isolated in situ, has been measured in anaesthetized cats by a radio-isotopic method. The effects of irritation of various parts of the airway on this mucus output were studied. 2. Mechanical stimulation of the nose and nasopharynx increased tracheal mucus output by reflexes which involved parasympathetic and probably also sympathetic motor pathways. 3. Laryngeal stimulation had a similar through the same motor pathways. 4. Inhalation of ammonia vapour into the lower airways reflexly increased mucus output from the isolated trachea. The efferent pathway for this reflex was mainly or entirely parasympathetic. It is argued that the afferent pathway involved cough receptors. 5. Lung inflation, inhalation of histamine aerosol and intravenous injection of phenyl diguanide (which excite mainly lung stretch receptors, lung 'irritant' receptors and alveolar 'J-receptors' respectively) had no consistent effect on tracheal mucus secretion. 6. The afferent and efferent pathways of these reflexes are discussed.

Muscle relaxation by drugs which stimulate sensory nerve endings—I. The effect of veratrum alkaloids, phenyldiguanide and 5-hydroxytryptamine

Phenyldiguanide and veratridine, given to cats i.v. or into the right atrium in doses of 25–100 and 6–25 μg/kg, were found to depress “spontaneous” EMG activity and muscle tone in “gamma-type” decerebrate preparations and in animals under light chloralose-urethane anaesthesia. The depression of motor activity involved both extensor and flexor muscles and was abolished by bilateral mid-cervical vagotomy. The effect was less consistent and more often preceded by initial increases in activity in the decerebrate cat than in experiments under anaesthesia, and also required doses in the upper portion of the ranges shown. Protoveratrine and veratrine also produced vagus-dependent depression of spontaneous motor activity. Reflex motor depression and reflex hypotension frequently began simultaneously, suggesting that both effects arose from the same type of receptor. The latent periods of the effect of phenyldiguanide following intra-atrial injection were 1 1 2 –2 1 2 sec, and are thus in agreement with those found by paintal (1957 and 1964) for the stimulation of pulmonary deflation receptors. The effect of phenyldiguanide was duplicated and subsequently blocked by naphthylguanidine. The latent periods of the veratridine effects ranged between 4–6 sec; ventricular pressure and/or lung stretch receptors are considered as probable sites of reflex initiation. The hypotensive responses were not the cause of the somatic effects. 5-Hydroxytryptamine (5-HT) also depressed motor activity, at least part of its action being attributable to excitation of deflation receptors. All three types of drugs reduced the patellar tendon reflex by a slight to moderate degree in more than half of the experiments.

Discharge patterns of the lung stretch receptors and activation of deflation fibres in anaphylactic bronchial asthma

The activity of single pulmonary stretch receptors was studied in guinea-pigs in order to elucidate the changes in the mechanical properties of the lungs which underlie vagal deflation receptor activity and hence the activation of respiration during an asthma attack. In anaphylactic bronchial asthma the activity of the stretch receptors varies from receptor to receptor, but also in one and the same unit. A small part of the receptors show decreased, the majority unchanged or — particularly during expiration — increased activity. The changes in the discharge patterns in the course of an attack are, however, reversible. Analogous results are also found in histamine induced asthma. The heterogeneous changes of the stretch receptor activity signal the heterogeneous changes in the mechanical behaviour, i.e, uneven ventilation of the corresponding lung units. Typical stretch receptor discharge patterns are discussed in relation to the mechanical behaviour of the lung units during the asthma attack, and the possible site of the receptors. The results presented indicate that uneven ventilation underlies the activation of the lung deflation reflex and the respiratory effects of the pulmonary stretch receptors during an asthma attack.

Effect of circulation in the lungs on functional state of the lung stretch receptors

Effect of circulation in the lungs on functional state of the lung stretch receptors

Zur Frage der Receptorspezifit�t endoanaesthetischer Wirkungen am Beispiel des Benzononatin (Tessalon)

1. Using electrophysiological techniques, the endoanesthetic effect of benzononatin (Tessalon, Ciba AG) on peripheral receptive endings was studied in dogs and cats, slightly anesthetized with chloralose or nembutal. 2. Because of its localanesthetic properties, Tessalon (1 – 5 mg/kg i.v.) paralyses lung stretch receptors, baroceptors of the aortic arch, left and right atrial receptors, primary and secondary muscle spindle endings and chemoreceptors. 3. Differences in strength and duration of the “endoanesthetic” effect depend on several factors: slowly adapting receptors show a more pronounced desensitation for a longer time than do quickly adapting receptors, a fact, which agrees with results on generator potentials. The contact concentration of the endoanesthetic agent on the receptor is influenced by dosage/time, site of application and anatomical localisation of the receptor related to the blood vessels.

Zum Mechanismus des reflektorischen Atemstillstandes nach intraven�ser Injektion von Chlorpromazin

Transient stop of respiration in exspiratory position can be produced in cats by intravenous injection of chlorpromazine, promethazine, and diethazine. The effect is dependend on the velocity of injection and on the concentration of the injected solution. Furthermore, it is most powerfull after administration into the arteria pulmonalis, but cannot be recognised after injection into the vena pulmonalis or into the bulbus aortae. It is abolished by vagotomia, but not by cooling both vagi to 6°C. Records of afferent vagal impulses at this temperature don't provide evidence for activation of lung stretch receptors. The alterations of blood pressure in the arteria et vena pulmonalis develop slowly and are only small. Therefore the chemosensible pulmonary vascular receptors are supposed to be chiefly involved in the reflectory stop of respiration after chlorpromazine, promethazine, and diethazine.

Mechanics of breathing in man.

Mechanics of breathing in man.