Antagonistic interaction of laryngeal and central chemoreceptor respiratory reflexes

Stimulation of laryngeal afferent fibers evokes a profound reflex inhibition of central respiratory drive. The interaction of this airway reflex with chemoreceptive ventilatory control mechanisms is poorly understood. The present study was undertaken to determine whether there is significant interaction between the effects of central chemoreceptor and laryngeal afferent stimulation on central inspiratory activity and, if so, to also determine the nature of the interaction. The effect of electrical stimulation of the superior laryngeal nerve (SLN) on the timing and intensity of central inspiratory activity was determined from the rectified and filtered phrenic neurogram in 10 dogs. Each dogs was decerebrated, artificially ventilated, vagotomized, and had the carotid bodies denervated. In each case, stimulation of the right SLN at 3 and 10 Hz caused a frequency-dependent slowing or arrest of central inspiratory activity. Increases in arterial PCO2 (PaCO2) attenuated the absolute level of inhibition of central inspiratory activity recorded during both SLN stimulation and control periods. Tp clarify the nature of the interaction between chemoreceptor and laryngeal afferent stimulation, the relationship between PaCO2 and central inspiratory activity was investigated during stimulation of the SLN at 0, 3, and 10 Hz. Control central inspiratory activity increased as a sigmoidal function of PaCO2. This sigmoidal relationship was greatly depressed during SLN stimulation but did not appear to be shifted along the PaCO2 axis. The results of this study therefore suggest that the interaction between central chemoreceptor and laryngeal afferent stimulation is multiplicative: the inhibition of the central inspiratory activity is mediated by an attenuation and not a resetting of central chemoreflexes.

Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).

Reflex cardiorespiratory responses to pulmonary vascular congestion

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.

Respiratory effects of progressive asphyxia in rabbit pups and adult rabbits

Effects of prolonged airway occlusion were investigated in anesthetized and vagotomized 9-to 15-day-old pups and adult rabbits. The changes and temporal relationships between “integrated” phrenic activity, external intercostal electromyogram (INT), and esophageal pressure (Pes) were examined. Each occlusion resulted in hyperpnea, apnea, and gasping. Blood pressure recorded during the occlusion showed a marked decrease. During hyperpnea, the rate of changes and maximal amplitudes in Pes and INT were similar in both age groups. The increase in integrated phrenic activity (PHR) was significantly greater in young rabbits. In both age groups, changes in INT during gasping followed a similar time course and exceeded those in PHR. Maximal values of the three parameters were concurrent in adults, whereas the increase in INT peaked later than PHR and Pes in rabbit pups. In adult rabbits, PHR, INT, and Pes, during the last gasp, decreased to the values of the first hyperpnea breath. In rabbit pups, Pes of the last gasp decreased significantly below this value while INT was still elevated. This Pes decrease could result from inspiratory muscle dysfunction in the pups. Thus in rabbit pups, 1) greater changes in PHR were necessary to produce a given change in Pes than in adult rabbits; 2) activity of the external intercostal muscles was not efficient in developing pressure under conditions of asphyxia; and 3) the independent activation of diaphragmatic and intercostal motoneurons is not of vagal origin. Additionally, the results led us to conclude that Pes can serve as a close approximation of respiratory drive in adult rabbits. This parameter, however, cannot be used as an index of central inspiratory activity during gasping in rabbit pups.

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory “duty cycle” (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.

Maturational effect of enkephalin on respiratory control in newborn rabbits

The respiratory responses to systemic infusion of the opioid peptide, [D-Ala2, D-Leu5]enkephalin (ENK) were determined in 39 unanesthetized tracheotomized rabbits (age range 1–20 days). At all ages, ventilation (VE), measured in a body plethysmograph, was depressed after ENK infusion in association with a decrease in CO2 elimination (VCO2) and body temperature. The degree of VE depression varied inversely with increasing age and was directly related to changes in mean inspiratory flow (i.e., VT/TI) while the ratio of inspiratory to total breath duration (TI/TT) was unaltered, except in rabbits under about 1 wk of age. Maturational differences in the VE response to ENK were related to age-dependent variation in the stability of the central inspiratory activity, which was manifested as periodic breathing with apnea in rabbits under about 5 days of age. Since the initial inspiratory volume-time profile was little affected by ENK and vagal afferent influence on respiration was not diminished, the depression in VE could be explained by an inhibition of the central inspiratory “off-switch” threshold and delay in central inspiratory “on-switching.” All effects of ENK were reversed by the opiate antagonist, naloxone.