Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

Influences from laryngeal afferents on expiratory bulbospinal neurons and motoneurons

The purpose of this study is to analyze the reflex effects of laryngeal afferent activation on respiratory patterns in anesthetized, vagotomized, paralyzed, ventilated cats. We recorded simultaneously from the phrenic nerve, T10 internal intercostal nerve, and single bulbospinal expiratory neurons of the caudal ventral respiratory group (VRG). Laryngeal afferents were activated by electrical stimulation of the superior laryngeal nerve (SLN) or by cold-water infusion into the larynx. Both types of stimuli caused inhibition of phrenic activity and facilitation of internal intercostal nerve activity, indicating expiratory effort. The activity of 46 bulbospinal expiratory cells was depressed during SLN electrical stimulation, and 13 of them were completely inhibited. In 44 of 56 neurons tested, mean firing frequency (FFmean) was decreased in response to cold-water infusion and 8 others responded with increased FFmean; in the remaining 4 neurons, FFmean was unchanged. Possible reasons for different neuronal responses to SLN electrical stimulation and water infusion are discussed. We conclude that bulbospinal expiratory neurons of VRG were not the source of the reflex motoneuronal expiratory-like activity produced by SLN stimulation. Other, not yet identified inputs to spinal expiratory motoneurons are activated during this experimental condition.     

Control of phrenic nerve activity and blood pressure by the medullary raphe nuclei in cats

Electrical and chemical stimulation methods were used to determine the topographic organization of the medullary raphe nuclei (MRN) in controlling the systemic arterial blood pressure (BP) and phrenic nerve activities (PNA). Decerebrated, unanesthetized and bilateral vagotomized cats were used. Effective points in the MRN were systematically explored with constant current stimulation. We found stimulation of the rostral MRN produced a decrease in PNA amplitude and increase in BP and PNA frequency. Stimulation of the caudal MRN produced increases in BP and the amplitude and frequency of PNA. Microinjection of glutamate solution into the caudal or the rostral MRN points produced qualitatively similar results. Thus, we concluded that the caudal MRN neurons had excitatory connections whereas the rostral MRN neurons had excitatory and inhibitory connections to the cardiovascular preganglionic neurons and the phrenic nerve motoneurons.     

Central GABAergic mechanisms are involved in apnea induced by SLN stimulation in piglets.

Stimulation of the superior laryngeal nerve (SLN) results in apnea in animals of different species, the mechanism of which is not known. We studied the effect of the GABA(A) receptor blocker bicuculline, given intravenously and intracisternally, on apnea induced by SLN stimulation. Eighteen 5- to 10-day-old piglets were studied: bicuculline was administered intravenously to nine animals and intracisternally to nine animals. The animals were anesthetized and then decerebrated, vagotomized, ventilated, and paralyzed. The phrenic nerve responses to four levels of electrical SLN stimulation were measured before and after bicuculline. SLN stimulation caused a significant decrease in phrenic nerve amplitude, phrenic nerve frequency, minute phrenic activity, and inspiratory time (P < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea during stimulation that often persisted beyond cessation of the stimulus. Bicuculline, administered intravenously or intracisternally, decreased the SLN stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency (P < 0.05). Bicuculline also reduced SLN-induced apnea and duration of poststimulation apnea (P < 0.05). We conclude that centrally mediated GABAergic pathways are involved in laryngeal stimulation-induced apnea.     

家兔脊髓蛛网膜下腔注射乙酰胆碱对膈神经放电的影响

实验在50例麻醉、麻痹和切断双侧迷走神经的家兔上进行。用双极银丝电极引导膈神经放电,经放大、幅度积分而后记录在 X-Y 记录仪上。脊髓蛛网膜下腔注射乙酰胆碱(ACh)50μg 后,膈神经吸气放电幅度增加,平均增加30.6±11.6%.ACh 的这一效应可被阿托品阻断,但不能被六甲双铵、酚妥拉明和心得安阻断。但单独注射上述任何一种受体阻断剂均不能改变膈神经的放电活动。上述结果提示,脊髓蛛网膜下腔注射 ACh 可兴奋膈运动神经元,而且 ACh 的这一兴奋效应是由 Μ 受体中介的,但在正常生理情况下,胆碱能递质系统对膈神经元似无紧张性兴奋作用。因此,ACh 递质可能在脊髓水平对高级中枢下传的呼吸驱动信息的整合中起兴奋性调制作用。     

Enflurane depresses activity of the medullary inspiratory neurons in the cat

The effect of enflurane on the firing activity (spikes/sec) of the inspiratory neurons of the dorsal respiratory group (DRG) of the medulla oblongata was studied in decerebrate, paralyzed, mechanically ventilated cats before and after bilateral cervical vagotomy. Inspiratory neuronal activity, phrenic neurogram, arterial blood pressure, tracheal pressure, and end tidal CO2 concentration were recorded. Cells whose firing activity was in phase with that of the phrenic nerve were considered inspiratory neurons. Administration of 1 and 2% enflurane in oxygen produced gradual, significant, and dose-dependent depression of the cell activity with cervical vagi either intact or severed. Recovery of the cell activity occurred after termination of enflurane administration. In cats with intact vagi, 10 min after introduction of 1 and 2% enflurane, the cell activity (mean +/- SE) expressed as percentage of the control was 70 +/- 6% (P less than 0.05) and 48 +/- 5% (P less than 0.01), respectively. Bilateral cervical vagotomy did not affect the degree of cell depression due to enflurane. Hypercarbia induced by inhalation of 5% CO2 increased cell activity, but it did not block enflurane-induced cell depression, although it reduced it. It may be concluded that enflurane depresses the activity of the inspiratory neurons of the DRG. The results also suggest that the respiratory depressant effect of enflurane has a central component and that the DRG region may serve as a site to mediate the enflurane-induced respiratory depression.     

Respiratory rhythmicity in the cat.

Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have "classical" responses and others have "paradoxical" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops.     

Influences of superior laryngeal afferent stimulation on expiratory activity in cats

The effects of superior laryngeal nerve (SLN) stimulation on the activity of the expiratory muscles and medullary expiration-related (ER) neurons were investigated in 24 pentobarbital-anesthetized cats. In some experiments the animals were also paralyzed and artificially ventilated. Sustained tetanic stimulation of SLN consistently caused an apneic response associated with the appearance of tonic CO2-dependent activity in the expiratory muscles and in ER neurons located in the caudal ventral respiratory group (VRG) and the B?tzinger complex. Single shocks or brief tetani at the same stimulation intensities failed to evoke excitatory responses in the expiratory muscles and in the vast majority of ER neurons tested. At higher stimulation strengths, single shocks or short tetani elicited excitatory responses in the expiratory muscles (20- to 35-ms latency) and in the majority of ER neurons of the caudal VRG (7.5- to 15.5-ms latency). These responses were obtained only during the expiratory phase and proved to be CO2 independent. On the contrary, only inhibitory responses were evoked in the activity of B?tzinger complex neurons. The observed tonic expiratory activity most likely represents a disinhibition phenomenon due to the suppression of inspiratory activity; activation of expiratory muscles at higher stimulation intensities appears to be a polysynaptic reflex mediated by ER neurons of the caudal VRG but not by B?tzinger complex neurons.     

Central inspiratory influence on abdominal expiratory nerve activity

Our purpose was to determine whether the intensity of abdominal expiratory nerve discharge is conditioned by the intensity of the preceding inspiratory phrenic discharge, independent of mechanical and chemical afferent influences. In decerebrate, paralyzed, vagotomized cats with bilateral pneumothoraxes, we recorded phrenic and abdominal (cranial iliohypogastric nerve, L1) nerve activities at hyperoxic normocapnia. We reduced the duration and intensity (i.e., integrated peak height) of phrenic nerve discharge for single cycles by stimulating the cut central end of the superior laryngeal nerve (SLN) during the central inspiratory phase (75 microA, 20-50 Hz, 0.2-ms pulse). Premature termination of inspiration consistently reduced expiratory duration (TE) and abdominal expiratory nerve activity (area of integrated neurogram), but the average reduction in TE was much less than the reduction in abdominal nerve activity (14 vs. 51%). Stimulation of the cut central end of the vagus nerve yielded similar results, as did spontaneous premature terminations of inspiration, which we observed in one cat. SLN stimulation during hyperoxic hypercapnia resulted in more variable responses, and higher stimulation frequencies were usually required to abort inspiration. SLN (or vagal) stimulation during expiration consistently increased abdominal expiratory nerve activity. We speculate that this facilitatory response is gated during inspiration, thereby allowing the inspiratory conditioning effect on the subsequent expiration to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recovery of phrenic activity and ventilation after cervical spinal hemisection in rats.

We tested two hypotheses: 1) that the spontaneous enhancement of phrenic motor output below a C2 spinal hemisection (C2HS) is associated with plasticity in ventrolateral spinal inputs to phrenic motoneurons; and 2) that phrenic motor recovery in anesthetized rats after C2HS correlates with increased capacity to generate inspiratory volume during hypercapnia in unanesthetized rats. At 2 and 4 wk post-C2HS, ipsilateral phrenic nerve activity was recorded in anesthetized, paralyzed, vagotomized, and ventilated rats. Electrical stimulation of the ventrolateral funiculus contralateral to C2HS was used to activate crossed spinal synaptic pathway phrenic motoneurons. Inspiratory phrenic burst amplitudes ipsilateral to C2HS were larger in the 4- vs. 2-wk groups (P<0.05); however, no differences in spinally evoked compound phrenic action potentials could be detected. In unanesthetized rats, inspiratory volume and frequency were quantified using barometric plethysmography at inspired CO2 fractions between 0.0 and 0.07 (inspired O2 fraction 0.21, balance N2) before and 2, 3, and 5 wk post-C2HS. Inspiratory volume was diminished, and frequency enhanced, at 0.0 inspired CO2 fraction (P<0.05) 2-wk post-C2HS; further changes were not observed in the 3- and 5-wk groups. Inspiratory frequency during hypercapnia was unaffected by C2HS. Hypercapnic inspiratory volumes were similarly attenuated at all time points post-C2HS (P<0.05), thereby decreasing hypercapnic minute ventilation (P<0.05). Thus increases in ipsilateral phrenic activity during 4 wk post-C2HS have little impact on the capacity to generate inspiratory volume in unanesthetized rats. Enhanced crossed phrenic activity post-C2HS may reflect plasticity associated with spinal axons not activated by our ventrolateral spinal stimulation.     

Cervical sympathetic and phrenic nerve responses to progressive brain hypoxia

To determine if depression of central respiratory output during progressive brain hypoxia (PBH) can be generalized to other brain stem outputs, we examined the effect of PBH on the tonic (tSCS) and inspiratory-synchronous (iSCS) components of preganglionic superior cervical sympathetic (SCS) nerve activity. Peak phrenic and SCS activity were measured in nine anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats. PBH was produced by inhalation of 0.5% CO in 40% O2 while blood pressure and end-tidal CO2 were maintained constant. A progressive reduction in arterial O2 content from 14.3 +/- 0.6 to 4.5 +/- 0.3 vol% caused a 79 +/- 7% depression of peak phrenic activity and an 84 +/- 10% reduction of iSCS activity, but tSCS activity increased 42 +/- 21%. During CO2 rebreathing, iSCS activity increased in parallel with peak phrenic activity while tSCS activity was unchanged. The slopes of the CO2 responses of both phrenic (6.3 +/- 1.2%max/mmHg) and iSCS (4.6 +/- 0.8%max/mmHg) activity were unaffected by PBH. In four of nine hypocapnic and three of nine hypoxic studies, inspiratory activity in the SCS nerve was observed even after completely silencing the phrenic neurogram.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of central adenosine A(2A) receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway.

Activation of the laryngeal mucosa results in apnea that is mediated through, and can be elicited via electrical stimulation of, the superior laryngeal nerve (SLN). This potent inhibitory reflex has been suggested to play a role in the pathogenesis of apnea of prematurity and sudden infant death syndrome, and it is attenuated by theophylline and blockade of GABA(A) receptors. However, the interaction between GABA and adenosine in the production of SLN stimulation-induced apnea has not been previously examined. We hypothesized that activation of adenosine A(2A) receptors will enhance apnea induced by SLN stimulation while subsequent blockade of GABA(A) receptors will reverse the effect of A(2A) receptor activation. The phrenic nerve responses to increasing levels of SLN stimulation were measured before and after sequential intracisternal administration of the adenosine A(2A) receptor agonist CGS (n = 10) and GABA(A) receptor blocker bicuculline (n = 7) in ventilated, vagotomized, decerebrate, and paralyzed newborn piglets. Increasing levels of SLN stimulation caused progressive inhibition of phrenic activity and lead to apnea during higher levels of stimulation. CGS caused inhibition of baseline phrenic activity, hypotension, and enhancement of apnea induced by SLN stimulation. Subsequent bicuculline administration reversed the effects of CGS and prevented the production of apnea compared with control at higher SLN stimulation levels. We conclude that activation of adenosine A(2A) receptors enhances SLN stimulation-induced apnea probably via a GABAergic pathway. We speculate that SLN stimulation causes endogenous release of adenosine that activates A(2A) receptors on GABAergic neurons, resulting in the release of GABA at inspiratory neurons and subsequent respiratory inhibition.     

Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mu-opioid receptor agonist effects on medullary respiratory neurons in the cat: evidence for involvement in certain types of ventilatory disturbances

Mu-opioid receptor agonists depress tidal volume, decrease chest wall compliance, and increase upper airway resistance. In this study, potential neuronal sites and mechanisms responsible for the disturbances were investigated, dose-response relationships were established, and it was determined whether general anesthesia plays a role. Effects of micro-opioid agonists on membrane properties and discharges of respiratory bulbospinal, vagal, and propriobulbar neurons and phrenic nerve activity were measured in pentobarbital-anesthetized and unanesthetized decerebrate cats. In all types of respiratory neurons tested, threshold intravenous doses of the micro-opioid agonist fentanyl slowed discharge frequency and prolonged duration without altering peak discharge intensity. Larger doses postsynaptically depressed discharges of inspiratory bulbospinal and inspiratory propriobulbar neurons that might account for depression of tidal volume. Iontophoresis of the micro-opioid agonist DAMGO also depressed the intensity of inspiratory bulbospinal neuron discharges. Fentanyl given intravenously prolonged discharges leading to tonic firing of bulbospinal expiratory neurons in association with reduced hyperpolarizing synaptic drive potentials, perhaps explaining decreased inspiratory phase chest wall compliance. Lowest effective doses of fentanyl had similar effects on vagal postinspiratory (laryngeal adductor) motoneurons, whereas in vagal laryngeal abductor and pharyngeal constrictor motoneurons, depression of depolarizing synaptic drive potentials led to sparse, very-low-frequency discharges. Such effects on three types of vagal motoneurons might explain tonic vocal fold closure and pharyngeal obstruction of airflow. Measurements of membrane potential and input resistance suggest the effects on bulbospinal Aug-E neurons and vagal motoneurons are mediated presynaptically. Opioid effects on the respiratory neurons were similar in anesthetized and decerebrate preparations.     

Phrenic afferents and their role in inspiratory control

In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.     

反射性呼吸暂停中延髓各类呼吸性神经元的放电变化

在向家兔颈动脉窦区注入拘椽酸钠引起呼吸暂停期间,和在持续性肺充气引起延长的呼气相中,延髓大多数吸气神经元和膈神经停止放电;而大多数呼气性神经元呈连续性放电,放电频率持续地高于或接近于平静呼气时呼气神经元的高峰放电频率,并伴随肋间内肌电活动增强,直至呼气性神经元放电频率衰减或停止放电时,膈神经才恢复放电。这提示呼气性神经元的持续兴奋状态可能与呼气性呼吸暂停的维持或呼气相的延长有关。在延髓闩前部可以记录到少数放电频率渐增型的跨时相呼气-吸气神经元,在呼吸暂停期间,它们呈低频连续放电,逐渐增大放电频率,在其放电频率急剧增高时,膈神经恢复放电。这提示该类神经元可能与吸气的发动有关。本文尚就呼吸节律的发生机制做了讨论。     

Influence of pulmonary inflations on discharge patterns of phrenic motoneurons

The purpose of this study was to assess the influence of pulmonary inflations on activities of single phrenic motoneurons. Studies were performed in decerebrate and paralyzed cats; activities of phrenic nerve and single phrenic motoneurons were recorded. Animals were ventilated with a servo-respirator which produced alterations in tracheal pressure in parallel with changes in integrated activity of the phrenic nerve. At end-tidal fractional concentrations of CO2 of 0.05, phrenic motoneurons were distributed into "early" and "late" populations, depending on time of onset of activity. During the late stages of neural inspiration, differences in levels of integrated activity of the phrenic nerve became evident between cycles with and without lung inflations. At a time approximating 90% of the inspiratory duration during inflations, integrated phrenic activity was higher for cycles with inflation. Concomitantly, with lung inflations, the discharge frequencies of early phrenic motoneurons were lower, and late motoneurons began to discharge sooner than when inflations were withheld. Similar results were obtained in hypercapnia. We conclude that reflexes activated by pulmonary inflations may produce augmentation, as well as inhibition of phrenic motoneuronal activities. Factors responsible for eliciting these reflex augmentations and inhibitions are discussed.     

Influence of lung volume on activities of branches of the recurrent laryngeal nerve

To investigate the influence of inspiratory lung inflation on the respiratory activities of laryngeal motor nerves, vagally intact decerebrate paralyzed cats were ventilated by a servorespirator in accordance with their own phrenic nerve activity. Records were made of the activities of the phrenic nerve, the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN), and the intralaryngeal branches of the RLN serving the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Neural activities were assessed in the steady state at different end-tidal O2 and CO2 concentrations. Transient responses to withholding inspiratory lung inflation and to preventing expiratory lung emptying were also studied. Hypercapnia and hypoxia increased the inspiratory activities of the phrenic nerve, SLN, RLN, and its PCA branch. TA inspiratory activity was not changed. Expiratory activities of RLN, PCA, and TA were all increased in hypoxia. When lung inflation was withheld, neural inspiratory duration and the inspiratory activities of all nerves increased. The subsequent period of neural expiration was marked by an exaggerated burst of activity by the TA branch of the RLN. TA expiratory activity was also sharply increased after inspiratory efforts that were reflexly delayed by the prevention of lung emptying. TA activity in expiration was enhanced after vagotomy and was usually more prominent than when lung inflation was withheld before vagal section. The results demonstrate the importance and complexity of the influence of vagal afferents on laryngeal motor activity.     

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.     

Recovery from central apnea: effect of stimulus duration and end-tidal CO2 partial pressure

The present study was designed to investigate the effect of stimulus duration and chemosensory input on the recovery of central respiratory activity from apnea induced by superior laryngeal nerve (SLN) electrical stimulation. Newborn piglets less than 8 days of age were anesthetized, paralyzed, and mechanically ventilated at differing levels of end-tidal CO2 partial pressure (PCO2). The vagi were cut bilaterally in the neck. Integrated phrenic nerve activity was used as the index of respiratory activity. SLN stimulation caused apnea that persisted after stimulus cessation. The length of apnea following stimulus cessation was directly related to stimulus duration and inversely related to end-tidal PCO2. After apnea, respiratory activity returned gradually to the initial control level. The recovery pattern was well described by a linear regression function using the natural logarithm of time as the independent variable. Prolonging stimulus duration progressively inhibited the amount of initial respiratory activity following apnea. On the other hand, the rate of respiratory recovery was independent of stimulus duration and, except at low end-tidal PCO2 following long (30 s) stimuli, was independent of the end-tidal PCO2 level. These results demonstrate that a long-acting central mechanism regulates recovery from apnea induced by SLN stimulation.