Spontaneous Augmented Breaths Research Articles

Impact of Dietary Folate on Respiratory Recovery after Cervical SCI

While much is known regarding folate's role in neural development, little is known concerning its effects in the adult central nervous system (CNS), particularly following injury or trauma. There is some evidence that folate enhances spinal sensory axon regrowth into a peripheral nerve graft after dorsal column injury. Further, 6 weeks after thoracic spinal contusion, folate supplementation elicits small but significant improvements in locomotor function in rats. Although surveys of individuals with chronic spinal cord injury (SCI) report reduced dietary folate intake, the impact folate intake on functional recovery after SCI is not known. Since respiratory dysfunction is the leading cause of death after cervical SCI, we investigated the effects of folate supplementation and deprivation on respiratory motor function after spinal hemisection at C2 (C2Hx). We hypothesized that folate supplementation would improve, while folate deprivation would hinder breathing recovery after C2Hx. In adult male Sprague Dawley rats with C2Hx, we compared the effects of a: 1) normal diet (4mg/kg folate in chow), 2) normal diet with supplemental folate injections (80ug/kg/day), and 3) folate deprivation (0 mg/kg folate in chow). Animals received their respective diets beginning 1 month prior to injury, and continued through the study duration. Intraperitoneal folate injections in the supplemented group were initiated 3 days prior to C2Hx and continued daily for 2 weeks post‐injury. Bilateral diaphragm electromyography (EMG) recordings were made in urethane anesthetized spontaneously breathing rats at 2 and 8 weeks post‐injury during normoxia (arterial PO2 ~90mmHg, PCO2 ~45mmHg), maximal chemoreceptor stimulation (10.5% O2/7% CO2), spontaneous augmented breaths (sighs), and sustained airway occlusion (40 sec). We did not see any consistent folate effects on ipsilateral or contralateral diaphragm EMG function at either 2 or 8 weeks post injury (P>0.05 for all). Sprouting of serotonergic projections near retrogradely labeled phrenic motoneurons were assessed via immunofluorescence, and quantification is in progress. Although we found no evidence that folate supplementation or deprivation impacts diaphragm function following C2Hx, this does not discount folate's potential role in mediating spinal respiratory motor plasticity or functional recovery in other models of CNS injury. For example, C2Hx severs all ipsilateral axons, with a >1mm gap. Since axonal growth and synapse formation is an innately slow process, the duration of this study may not have been sufficient to observe functional recovery mediated via axonal regrowth. Further studies are needed to rule out any role for folate in functional recovery following cervical SCI.Support or Funding InformationMcKnight Brain Institute, NIH SPARC OT 2OD023854, K12 HD055929, NIH T32 HD043730 and HL69064This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Compensatory plasticity in diaphragm and intercostal muscle utilization in a rat model of ALS

In SOD1G93A transgenic rat model of ALS, breathing capacity is preserved until late in disease progression despite profound respiratory motor neuron (MN) cell death. To explore mechanisms preserving breathing capacity, we assessed inspiratory EMG activity in diaphragm and external intercostal T2 (EIC2) and T5 (EIC5) muscles in anesthetized SOD1G93A rats at disease end-stage (20% decrease in body mass). We hypothesized that despite significant phrenic motor neuron loss and decreased phrenic nerve activity, diaphragm electrical activity and trans-diaphragmatic pressure (Pdi) are maintained to sustain ventilation. We alternatively hypothesized that EIC activity is enhanced, compensating for impaired diaphragm function. Diaphragm, EIC2 and EIC5 muscle EMGs and Pdi were measured in urethane-anesthetized, spontaneously breathing female SOD1G93A rats versus wild-type littermates during normoxia (arterial PO2 ~90mmHg, PCO2 ~45mmHg), maximal chemoreceptor stimulation (MCS: 10.5% O2/7% CO2), spontaneous augmented breaths and sustained tracheal occlusion. Phrenic MNs were counted in C3-5; T2 and T5 ventrolateral MNs were counted. In end-stage SOD1G93A rats, 29% of phrenic MNs survived (vs. wild-type), yet integrated diaphragm EMG amplitude was normal. Nevertheless, maximal Pdi decreased ~30% vs. wild type (p<0.01) and increased esophageal to gastric pressure ratio (p<0.05), consistent with persistent diaphragm weakness. Despite major T2 and T5 MN death, integrated EIC2 (100% greater than wild type) and EIC5 (300%) EMG amplitudes were increased in mutant rats during normoxia (p<0.01), possibly compensating for decreased Pdi. Thus, despite significant phrenic MN loss, diaphragm EMG activity is maintained; in contrast, Pdi was not, suggesting diaphragm dysfunction. Presumably, increased EIC EMG activity compensated for persistent diaphragm weakness. These adjustments contribute to remarkable preservation of breathing ability despite major respiratory motor neuron death and diaphragm dysfunction.

The effects of five clinically relevant narcotic drugs on the generation of spontaneous augmented (sigh) breaths.

The prototypical μ‐opioid agonist, morphine, powerfully suppresses spontaneous augmented breaths (ABs). We previously found that this effect occurs at relatively low‐to‐moderate dosages, where traditional parameters of eupneic breathing (VT and f) are not overtly affected. Based upon the heterogeneity of pharmacological properties among commonly prescribed opioid medications, we hypothesized that the suppression of ABs would be significantly different in the presence of opioid drugs other than morphine. To test this, we studied 6 adult male rats (534±47g, range=402–637g) using a randomized cross‐over repeated‐measures design to evaluate the effects of 5 common narcotics on the rate of ABs during spontaneous breathing in unanesthetized and unrestrained adult male rats, monitored using hybrid sealed‐chamber and open‐flow plethysmography. Drugs were administered via s.c. injection at the following doses: Morphine: 0, 1.0, 2.0, 3.0 mg/kg; Fentanyl: 0, 0.02, 0.03, 0.04 mg/kg; Methadone: 0, 1.0, 2.5, 4.0 mg/kg; Buprenorphine: 0, 0.01, 0.03, 0.05 mg/kg; Oxycodone: 0, 0.5, 1.0, 1.5 mg/kg (0 mg/kg = saline sham dose). All animals received all drugs and dosages in randomized order. Doses were chosen to achieve a range up to and including analgesic effectiveness to prolong tail flick latency 2‐to‐3 fold over the sham injection. A tail flick analgesiometer was used to evaluate tail flick latency 15‐minutes post‐injection, followed by respiratory monitoring in ambient room air conditions for 30 minutes. Each animal completed a trial involving one dosage of one drug on a given day, with at least 48 hours between consecutive sessions. Drugs did not depress tidal volume or frequency of eupneic breathing. The baseline number of ABs observed following control injections for each drug condition were not different, ranging from 6.5 ± 1.4 to 7.3 ± 1.6 ABs/15mins, p=0.912. Each drug tested significantly decreased the number of spontaneous ABs in a dose‐dependent manner. The number of ABs observed at the highest drug dosages were 1.5 ± 1.3 (mor), 1.3 ± 1.0 (fen), 0.8 ± 1.2 (met), 0.0 ± 0.0 (bup), and 1.7 ± 1.2 (oxy) ABs/15mins (p&lt;0.001 for all changes vs sham). The relationship between ABs and analgesic effect (i.e. %increase in tail flick latency vs. % of ABs remaining in the breathing rhythm) followed a 2‐parameter single exponential decay model. Significant relationships were identified between analgesic effect and suppression of ABs for all drugs tested (p&lt;0.05) with the exception of oxycodone wherein the relationship narrowly failed to reach statistical significance (p=0.058). The strongest relationship existed within the buprenorphine condition (rs=.764, p&lt;0.001). Buprenorphine also yielded the lowest analgesic effect required to produce a 50% suppression in ABs (observed at 16% prolongation in tail flick latency). Our results demonstrate that the suppression of ABs is a ubiquitous side effect of common narcotic drugs across the low‐moderate analgesic range, and is therefore unlikely to be mitigated by selective avoidance of specific opioids/opiates. Further, the unique potency of buprenorphine in suppressing ABs suggests that complex opioid receptor interactions may be of key mechanistic importance in mediating this effect.Support or Funding InformationCK was supported by a Summer Scholars Research Program Award through the CMU College of Medicine. HB received research support from an Early Career Award through the Office of Research and Sponsored Programs at CMU, and operating funds from the CMU College of Medicine.

Role of Na+ and Ca2+ currents in computational model of in-vitro sigh generation

Eupneic breathing in mammals is periodically interrupted by spontaneous augmented breaths (sighs) that are characterized by a biphasic larger-amplitude inspiratory burst followed by post-sigh apnea. Previous in vitro studies in newborn rodents have demonstrated that the respiratory oscillator of the pre-Botzinger complex (preBotC) can generate the distinct inspiratory-related motor patterns for both eupnea- and sigh-like activity [1,2]. However it remains debated whether these two types of inspiratory activities are produced by the same neuronal population or by distinct sub-networks. Based on recent in vitro data obtained in the mouse embryo [3], we have built a computational model consisting of two compartments, one dedicated to sigh generation and the other generating eupneic bursts, interconnected through appropriate synapses (Figure ​(Figure11 A). Figure 1 Sigh and eupnea activity pattern in silico. (A) Diagrams of sigh (left) and eupnea (right) network models. Except for the ER capacity, INaP and Ih, the sigh and eupnea models are identical. (B) Intracellular Ca2+ (top) and voltage (bottom) obtained for ... The model reproduces basic features of simultaneous sigh and eupnea generation: two types of bursts differing in terms of shape, amplitude and frequency of occurrence and mimics the effect of glycinergic synapses blockade. We designed a two-compartment computational model for sigh and eupnea subpopulations of neurons with several different parameters reflecting distinct burst generating mechanisms. The sigh subpopulation generates a low frequency rhythm based on slow intracellular Ca2+ oscillations and the eupnea subnetwork generates fast oscillations mainly driven by activation/inactivation of the persistent Na+ current (Fig 1 B,C).Furthermore, we used this model to make predictions that were subsequently tested on the isolated preBotC in brainstem slice preparations. Through a combination of our in vitro and in silico approaches we found that 1), sigh events are less sensitive to network excitability than eupneic activity, 2)The combination of voltage-gated calcium current and persistent sodium current control the sigh period of, and 3), specific parameters of Ih activation set the low sensitivity to excitability in the sigh neuronal subset. Altogether, our results strongly support the hypothesis that distinct subpopulations within the preBotC network are responsible for sigh and eupnea rhythmogenesis.

Emergence of sigh rhythmogenesis in the embryonic mouse

In mammals, eupnoeic breathing is periodically interrupted by spontaneous augmented breaths (sighs) that include a larger-amplitude inspiratory effort, typically followed by a post-sigh apnoea. Previous in vitro studies in newborn rodents have demonstrated that the respiratory oscillator of the pre-Bötzinger complex (preBötC) can generate the distinct inspiratory motor patterns for both eupnoea- and sigh-related behaviour. During mouse embryonic development, the preBötC begins to generate eupnoeic rhythmicity at embryonic day (E) 15.5, but the network's ability to also generate sigh-like activity remains unexplored at prenatal stages. Using transverse brainstem slice preparations we monitored the neuronal population activity of the preBötC at different embryonic ages. Spontaneous sigh-like rhythmicity was found to emerge progressively, being expressed in 0/32 slices at E15.5, 7/30 at E16.5, 9/22 at E17.5 and 23/26 at E18.5. Calcium imaging showed that the preBötC cell population that participates in eupnoeic-like discharge was also active during fictive sighs. However, patch-clamp recordings revealed the existence of an additional small subset of neurons that fired exclusively during sigh activity. Changes in glycinergic inhibitory synaptic signalling, either by pharmacological blockade, functional perturbation or natural maturation of the chloride co-transporters KCC2 or NKCC1 selectively, and in an age-dependent manner, altered the bi-phasic nature of sigh bursts and their coordination with eupnoeic bursting, leading to the generation of an atypical monophasic sigh-related event. Together our results demonstrate that the developmental emergence of a sigh-generating capability occurs after the onset of eupnoeic rhythmogenesis and requires the proper maturation of chloride-mediated glycinergic synaptic transmission.

The “other” respiratory effect of opioids: suppression of spontaneous augmented (“sigh”) breaths

The purpose of this study was to examine the effects of a clinically relevant opioid on the production of augmented breaths (ABs) in unanesthetized animals breathing normal room air, using a dosage which does not depress breathing. To do this we monitored breathing noninvasively, in unrestrained animals before and after subcutaneous injection of either morphine, or a saline control. The effect of ketamine/xylazine was also studied to determine the potential effect of an alternative sedative agent. Last, the effect of naloxone was studied to determine the potential influence of endogenous opioids in regulating the normal incidence of ABs. Morphine (5 mg/kg) had no depressive effect on breathing, but completely eliminated ABs in all animals in room air (P = 0.027). However, when animals breathed hypoxic air (10% O(2)), animals did express ABs, although their incidence was still reduced by morphine (P < 0.001). This was not a result of sedation per se, as ABs continued at their normal rate in room air during sedation with ketamine. Naloxone had no effect on breathing or AB production, and so endogenous opioids are not likely involved in regulating their rate of production under normal conditions. Our results show that in unanesthetized animals breathing normal room air, a clinically relevant opioid eliminates ABs, even at a dose that does not cause respiratory depression. Despite this, hypoxia-induced stimulation of breathing can facilitate the production of ABs even with the systemic opioid present, indicating that peripheral chemoreceptor stimulation provides a potential means of overcoming the opioid-induced suppression of these respiratory events.

Respiratory alkalosis is the determinant of the increased production of augmented breaths triggered by hypoxia

Spontaneous augmented breaths (ABs) are large, transient respiratory disturbances which often lead to apneas or instability in subsequent breath cycles. Hypoxia is known to increase the rate of occurrence of ABs, however the underlying factors mediating this effect are not fully understood. In this study, we examined the role of hypocapnia in the hypoxia‐induced increase in ABs. In studying the ventilatory responses of 5 freely behaving adult rats (489 ± 22 g), we found that an average of 1.0 ± 0.7 ABs occurred in room air (RA) in a standardized 5 minute observation window. Exposure to hypoxia (~10% FiO2) caused a dramatic increase in the number of ABs (13 ± 1.5 in 5 min, P&lt;0.001). When hypoxia was supplemented with 5 % CO2 in the inspired air, the number of ABs returned to a level close to RA conditions (2.4 ± 0.5 p&lt;0.001). CO2 alone had no significant effect. Acetazolamide treatment (100 mg/kg IP 2x/d, for 48 hrs) was found to effectively eliminate the increased prevalence of ABs normally observed during exposure to hypoxia. We therefore conclude that hypoxia promotes the generation of augmented breaths, but only when hypocapnia‐induced alkalosis develops. We further speculate that ABs during hypoxia are expressed as a result of an increased neuronal excitability related to acute respiratory alkalosis. This study received internal funding support from the Heart and Vascular Institute, Penn State College of Medicine.

The effects of MK-801 on spontaneous augmented breaths in normoxic and hypoxic unanesthetized rats

The effects of MK-801 on spontaneous augmented breaths in normoxic and hypoxic unanesthetized rats

Effects of GABA A and glycine receptor agonists on the medullary inspiratory neuronal activity during spontaneous augmented breaths in anesthetized rats

To clarify whether GABAergic or glycinergic transmission alters the activity of inspiratory neurons during spontaneous augmented breaths, we recorded the single unit activity from inspiratory neurons in the dorsal and ventral respiratory groups in the medulla of pentobarbital anesthetized rats and applied GABA A and glycine receptor agonists by iontophoresis using multibarrel microelectrodes. The spontaneous augmented breath was divided into two different phases; the first phase (phase I) resembled a normal inspiration but the second phase (phase II) indicated a marked increase in diaphragm electromyogram activity. During application of either muscimol or glycine, the discharge of inspiratory neurons during the phase I of spontaneous augmented breaths was suppressed, but the augmenting discharge of the phase II did not change significantly in any cell type of the neurons (I-augmenting, I-decrementing and I-other). These results suggested that the excitatory inputs to inspiratory neurons during the phase II of augmented breaths may not be significantly influenced by the activation of either GABA A receptors or glycine receptors.

Clonidine induces upper airway closure in awake goats.

We examined the effects of the alpha(2)-adrenoceptor (alpha(2)-AR) agonist clonidine on pressure-flow relationships in the upper airway. Inspired and expired airflows, subglottic tracheal pressure (PTR), mask pressure and middle pharyngeal constrictor (MPC) and diaphragm electromyogram (EMG) activities were recorded in awake standing goats. Clonidine-induced central apneas were always associated with continuous tonic activation of the MPC. Subglottic PTR during expiration increased progressively in a dose-dependent manner after clonidine administration. In all cases, positive subglottic PTR was maintained throughout the duration of clonidine-induced apneas and was sufficient to retard or prevent expiratory flow during early and mid-expiration indicating complete airway closure. The effects of clonidine were reversed by selective alpha(2)-AR blockade with SKF-86466. Central apneas after spontaneous augmented breaths (sighs) were associated with continuous tonic activation of the MPC throughout the duration of the prolonged TE intervals. However, subglottic PTR during expiration was not significantly different from control breaths and there was no evidence of increased expiratory airway resistance or delayed expiratory flow. We conclude that continuous tonic activation of pharyngeal adductor muscles appears to be a constant feature of central apnea in the awake goat independent of the initiating cause of the apnea. However, our data suggest that MPC activation alone may not be sufficient to cause complete closure of the upper airway during central apnea.

Consequences of periodic augmented breaths on tongue muscle activities in hypoxic rats.

This study was designed to investigate the influence of hypoxia-evoked augmented breaths (ABs) on respiratory-related tongue protrudor and retractor muscle activities and inspiratory pump muscle output. Genioglossus (GG) and hyoglossus (HG) electromyogram (EMG) activities and respiratory-related tongue movements were compared with peak esophageal pressure (Pes; negative change in pressure during inspiration) and minute Pes (Pes x respiratory frequency = Pes/min) before and after ABs evoked by sustained poikilocapnic, isocapnic, and hypercapnic hypoxia in spontaneously breathing, anesthetized rats. ABs evoked by poikilocapnic and isocapnic hypoxia triggered long-lasting (duration at least 10 respiratory cycles) reductions in GG and HG EMG activities and tongue movements relative to pre-AB levels, but Pes was reduced transiently (duration of <10 respiratory cycles) after ABs. Adding 7% CO(2) to the hypoxic inspirate had no effect on the frequency of evoked ABs, but this prevented long-term declines in tongue muscle activities. Bilateral vagotomy abolished hypoxia-induced ABs and stabilized drive to the tongue muscles during each hypoxic condition. We conclude that, in the rat, hypoxia-evoked ABs 1) elicit long-lasting reductions in protrudor and retractor tongue muscle activities, 2) produce short-term declines in inspiratory pump muscle output, and 3) are mediated by vagal afferents. The more prolonged reductions in pharyngeal airway vs. pump muscle activities may lead to upper airway narrowing or collapse after spontaneous ABs.

Respiratory-related pharyngeal constrictor muscle activity in awake goats

Respiratory-related electromyogram (EMG) activities of the middle (MPC) and inferior (IPC) pharyngeal constrictor (PC) muscles were determined simultaneously with up to six additional upper airway abductor and adductor muscles in awake adult goats. Phasic PC activation began in late inspiration and persisted throughout expiration with a steady, an augmenting or a biphasic pattern of activity. Considerable differences were noted in the EMG responses of the MPC and IPC muscles to respiratory-related stimuli. During hypoxia and hypercapnia, phasic MPC activity decreased or was not recruited whereas phasic IPC activity was augmented with increased chemical drive. During spontaneous augmented breaths and peripheral chemoreceptor stimulation with sodium cyanide, the pattern of activation of the MPC was similar to that of the thyroarytenoid muscle (TA), a laryngeal adductor whereas IPC activity was strikingly similar to activity of the laryngeal and pharyngeal dilators. The expiratory portion of an augmented breath was associated with increased phasic MPC and TA but not IPC activities. Dopamine-induced apneas resulted in tonic activation of the MPC and TA at a level equal to or greater than control activity but no recruitment of IPC activity. The marked differences in MPC and IPC responses to respiratory-related stimuli suggests that these muscles may have different mechanical effects on pharyngeal airway caliber in the goat. The results suggest that the MPC may help brake expiratory flow thus helping to control expiratory timing and lung volume. In contrast, the IPC may promote pharyngeal airway patency by stiffening or dilating the pharyngeal airway. The results demonstrate that a variety of stimuli can influence respiratory-related PC activity and suggest that the PC muscles are important in the regulation of breathing and upper airway patency.

Effects of NMDA and non-NMDA receptor antagonists on the medullary inspiratory neuronal activity during spontaneous augmented breaths in anesthetized rats

To elucidate whether there is a difference between the effects of iontophoretically applied N-methyl- d-aspartate (NMDA) and non-NMDA receptor antagonists on the activity of inspiratory neurons during spontaneous augmented breaths, extracellular single unit recording of inspiratory neurons (I-augmenting, I-decrementing and I-other) was performed in pentobarbital anesthetized rats. The spontaneous augmented breath was divided into two different phases; the first phase (phase I) resembled a normal inspiration, but the second phase (phase II) consisted of a marked increase in diaphragm electromyogram activity. The mean firing frequency of I-aug type neurons was significantly decreased after 50 nA application of both d-2-amino-5-phosphonopentanoic acid (AP-5) (NMDA receptor antagonist) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (non-NMDA receptor antagonist). The mean firing frequency of both I-dec and I-other neurons was significantly decreased by both AP-5 and CNQX applications (70 nA). After AP-5 application, relative changes in the discharge rates during inspiratory phases I and II of spontaneous augmented breaths were significantly suppressed in all types of neurons, but CNQX application had no significant effect on the response changes during phase II. In all cell types of neurons, a significant difference between the iontophoretic AP-5 and CNQX applications in the relative mean firing rate was observed. These results suggested that activation of the NMDA receptor-induced neurotransmission can modify the discharge rate of medullary inspiratory neurons, irrespective of the cell types, during the inspiratory phase II of spontaneous augmented breaths, but that non-NMDA receptor blockade may not significantly influence their discharge rate.

Effects of vagal and carotid chemoreceptor afferents on the frequency and pattern of spontaneous augmented breaths in rabbits.

We investigated the effects of vagal afferents and carotid chemoreceptors on the frequency and pattern of spontaneous augmented breaths in anesthetized rabbits by analyzing the changes in the phrenic nerve discharge. Blockade of vagal C-fiber conduction by capsaicin treatment greatly reduced the frequency of spontaneous augmented breaths but had no significant effect on the pattern of the augmented breaths. Inhalation of sulfur dioxide, which abolished the Hering-Breuer inflation reflex, suppressed the frequency of spontaneous augmented breaths but did not significantly alter the pattern of the augmented breaths. Carotid sinus denervation diminished both the frequency and amplitude of spontaneous augmented breaths. The occurrence of spontaneous augmented breaths was not observed in rabbits after bilateral vagotomy. In other experiments we examined the relationship between rapidly adapting pulmonary stretch receptors (RARs) and dynamic lung compliance during the spontaneous augmented breath. The stimulation of RARs occurred at the first phase of spontaneous augmented breaths, and augmentation of transpulmonary pressure seen at the second phase coincided with vigorous stimulation of the receptor activity. These results suggest that spontaneous augmented breaths may be mediated by the summation of several facilitatory inputs from vagal and carotid chemoreceptor afferents.

Medullary post-inspiratory neuronal and diaphragm post-inspiratory activities during spontaneous augmented breaths in anesthetized rats

To test the hypothesis that during augmented breaths the prolonged expiratory time is correlated with the activity of medullary post-inspiratory neurons, changes in diaphragm electromyogram and post-inspiratory neuronal activities were examined in pentobarbital anesthetized rats. During augmented breaths, the mean total expiratory time significantly increased (from 0.57 ± 0.02 to 1.20 ± 0.07 s, P < 0.01), but the mean duration of post-inspiratory inspiratory activity (PIIA) was significantly decreased (from 0.08 ± 0.01 to 0.02 ± 0.003 s, P < 0.01) compared to control breaths. The mean time which the diaphragm was electrically silent was observed to be significantly prolonged during augmented breaths (from 0.48 ± 0.02 to 1.19 ± 0.07 s, P < 0.01). During significant prolongations of expiratory time in augmented breaths, most of the recorded neurons ( 9 10 ) in the medulla showed sustained discharges. The mean duration of discharges was longer than that of PIIA (0.02 ± 0.003 vs.0.50 ± 0.10 s, P < 0.01). The mean firing frequency/breath significantly increased compared to control breaths (9.45 ± 1.69 vs 37.6 ± 7.13 imp/breath, P < 0.01). These results suggested that during augmented breaths, the prolonged expiratory period may not be mediated by persisting post-inspiratory neuronal activity in the medulla.

Discharge patterns of dorsal and ventral respiratory group neurons during spontaneous augmented breaths observed in pentobarbital anesthetized rats

To clarify the difference between the firing patterns of the dorsal respiratory group (DRG) and ventral respiratory group (VRG) neurons during spontaneous augmented breaths, extracellular single unit recording of 139 respiratory-related neurons (inspiratory: 98 139 , expiratory: 41 139 ) was performed in pentobarbital anesthetized rats. Both the I and E neurons were further classified into six groups: (1) I-augmenting, (2) I-decrementing, (3) I-other cells, (4) E-augmenting, (5) E-decrementing and (6) E-other cells. During the augmented breaths, most inspiratory neurons in the DRG ( 25 26 ) and VRG ( 67 72 ) show an increase in their discharge frequency irrespective of the cell type, but the discharges after an augmented breath were inhibited. Changes in these inspiratory neurons coincided with those of diaphragm electromyogram activity. With regard to relative changes in the mean firing rate during the inspiratory phase II of augmented breaths, there was a significant difference between the I-augmenting DRG and VRG neurons (353.5 ± 56.9% vs. 237.5 ± 17.1%, P < 0.01), but not in the I-decrementing and I-other neurons. On the other hand, the activities of the expiratory DRG ( 9 9 ) and VRG ( 27 32 ) neurons decreased during the augmented breath. A significant difference in the relative mean firing rate during the expiratory phase of augmented breaths was observed between the E-decrementing DRG and VRG neurons (27.3 ± 5.2% vs. 58.0 ± 6.3%, P < 0.05), but not between the E-augmenting and E-other neurons. These results suggested that during spontaneous augmented breaths the firing patterns of the DRG neurons were not qualitatively different from those of the VRG neurons.

Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters

Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters

EFFECT OF ACTIVE AND PASSIVE SIGHS IN NORMOXIA AND HYPEROXIA ON THE BREATHING OF PATIENTS ANAESTHETIZED WITH INFUSIONS OF PROPOFOL

Spontaneous augmented breaths (active sighs) reduced the tidal volume and inspiratory time of succeeding breaths; manual lung inflations (passive sighs) reduced the tidal volume but had little effect on inspiratory time. Sighs in air, whether active or passive, reduced tidal volume more than sighs in hyperoxia (100% oxygen or 33% oxygen in nitrous oxide) after both active and passive sighs (overall difference about 10%); the reduction in inspiratory time after a sigh was less affected by gas mixture. Calculated mean inspiratory flow was reduced after passive sighs, but active sighs were more likely to cause arousal, which complicated the analysis. Tidal volume was reduced after a sigh partly because of reduced peripheral chemoreceptor input, the main effect of which was to reduce inspiratory flow, and partly because inspiratory time was shorter. Although the chemoreceptors may affect inspiratory time after a sigh, the greater effect of active sighs compared with passive sighs makes it likely that the shortening was either part of the neural output that causes spontaneous sighs, or was caused by mechanoreceptor input not mimicked by manual lung inflation.

Respiratory-modulated and phrenic afferent-driven neurons in the cervical spinal cord (C4-C6) of the fluorocarbon-perfused guinea pig.

The potential contributions of cervical spinal interneurons to the neural control of respiration have been investigated by extracellularly recording the patterns of activity of neurons in the C4-C6 spinal cord during fictive respiration in the fluorocarbon-perfused, adult guinea pig. Two types of neurons were recorded: respiratory-modulated neurons, whose activity was modulated with respiration, and phrenic-driven neurons, which were excited by electrical stimulation of the phrenic nerve. Respiratory-modulated neurons (n = 20) could be divided into inspiratory, expiratory, and phase-spanning neurons, based on their patterns of activity during fictive respiration. Respiratory-modulated neurons showed varying dependencies on the type of breathing; during spontaneous augmented breaths, one-half exhibited patterns of activity that were significantly different to those seen during normal, fictive respiration, whereas the other half of the respiratory-modulated neurons showed similar patterns of activity during both normal and augmented breaths. Phrenic-driven neurons (n = 22) could be divided into short-latency (7-12 ms), moderate-latency (12-25 ms), and inhibited neurons, but were only occasionally and weakly modulated with respiration. The results suggest that respiratory-modulated C4-C6 spinal neurons may contribute to the neural control of respiration, with different subpopulations specialized for different types of respiratory tasks, and that phrenic-driven neurons may be interposed in sensory or reflex pathways, such as the spinothalamic tract or phrenic-to-phrenic inhibitory reflex.

Costal and crural diaphragm, and intercostal and genioglossal electromyogram activities during spontaneous augmented breaths (sighs) in kittens.

Spontaneously occurring augmented breaths (sighs) are common in infants. The pattern of electrical activity of the inspiratory muscles of the thorax and upper airway during augmented breaths, however, has not been fully characterized in this less than fully mature age group. We therefore examined costal and crural diaphragm and external intercostal and genioglossal EMG activities during spontaneous augmented breaths (n = 46) in 10 anesthetized (1.35% halothane) 1-month-old kittens breathing room air. EMG responses were assessed by comparing the spontaneous augmented breaths (AB) to the five immediately preceding breaths (control). The peak moving time average EMG activity observed during the AB was 240 +/- 32% (mean +/- SD) of control for the costal diaphragm, 279 +/- 66% of control for the crural diaphragm, and 274 +/- 68% of control for the external intercostal muscle. The mean increase in EMG activity during the AB was not significantly different among these three muscle groups (P greater than 0.25). Genioglossal EMG activity during AB was observed in only 1 of 10 study animals. These results document that during AB in anesthetized kittens, activity of the thoracic inspiratory muscles (costal/crural diaphragm and external intercostal muscles) increase in parallel, suggesting that they are modulated in a uniform manner. The infrequent observance of genioglossal activity during AB suggests that either 1) halothane anesthesia depresses genioglossal activity more than diaphragmatic and intercostal activity during AB or 2) that genioglossal recruitment is not necessary to maintain upper airway patency during this period of heightened respiratory drive.