Respiratory Discharge Research Articles

Development of respiratory function in perinatal ontogenesis

In development of respiratory function in rats, mice, and other representatives of placental animals there exists the general plan of formation of rhythm: from single contraction of respiratory musculature to formation of bursts and complexes alternating periodically with pauses and apnea intervals and subsequent rhythm stabilization. These peculiarities are closely connected with the states of sleep and consciousness. A concept is put forward about a certain sequence of functional maturation and ways of regulation of activity of the respiratory rhythm central pacemaker. At the first stage the autogenic rhythmical activity is determined by pacemaker properties of a part of neurons of the medulla rostral ventrolateral part. It is not ruled out that the first respiratory discharges in spinal cord ventral roots might have been a manifestation of the nervous network rhythmogenic properties. The direct sensitivity of central neurons to chemical composition if the medium and to some neutomodulators serves as the first regulatory mechanism. Somewhat later, inhibitory control is established from supramedullary structures, with an increase of role of peripheral receptors in regulation of respiration.

Diaphragm recovery by laryngeal innervation after bilateral phrenicotomy or complete C2 spinal section in rats

This study aimed to highlight the functional aspects of diaphragm reinnervation by laryngeal motoneurons after bilateral phrenicotomy or complete cervical transection. The left recurrent laryngeal nerve was connected to the left phrenic nerve in 14 rats. Five months later, all bridged rats presented a substantial ipsilateral diaphragm recovery (74.2 +/- 10% of contralateral activity) whereas the diaphragm remained paralysed in non-bridged rats (n = 5/5). After additional right phrenicotomy, functional breathing persisted in bridged rats whereas all non-bridged died. After complete C2 spinal transection, diaphragm respiratory discharges persisted in bridged rats. The reinnnervation by laryngeal motoneurons was confirmed by retrograde labeling, stimulus-elicited diaphragm response by vagal stimulation and diaphragm inactivation after vagotomy. In conclusion, the recurrent-phrenic nerve anastomosis induces a reliable functional diaphragm outcome even after contralateral diaphragm denervation or complete high cervical spinal cord injury, and could be considered as a clinical repair strategy for re-establishing diaphragm autonomy following spinal cord trauma.

Characteristics of drug concentration profiles for picoejection studies of brainstem neurons

The picoejection technique has been used to study the roles of various neurotransmitter receptors in the generation/control of respiratory neuronal discharge patterns. This method has the ability to produce quasi-steady-state dose-dependent effects on neuronal discharge frequency patterns. While the drug barrel concentration (Co) is known and ejection volume-rates can be measured, the drug concentration as a function of time and radial distance C(t,r) from the micropipette tip is not known. Accordingly, a mathematical compartmental model was developed and simulated, which allows the concentration profiles to be estimated for various diffusion rates and picoejection parameters. The model is based on Fick’s law (flux=-D.dC/dr, where D is the diffusion coefficient) and spherical geometry. Each of the 1020 compartments represents the volume of a 1-μm thick spherical shell centered at the tip of the pipette with the volume and surface area increasing with radial distance. The model gives C(t,r) in 1-μm increments for 0 < r < 1020 μm. Simulation shows that C(t,r) can reach ~90% of max. in 2 min for r<150 μm and peak C(t,r) is ~linearly related to ejection pulse rate and spritz volume over a wide C(t,r) range. The model allows picoejection strategies to be optimized. Support: VA Merit 9952 and NIH GM059234.

Spatiotemporal patterns of ventral medullary respiratory network activity during eupnea and gasping imaged using optical recording in situ

We investigated changes in the spatiotemporal pattern of respiratory network activity in the ventrolateral medulla during eupnea and hypoxic-induced gasping in situ. Part of the rostral ventrolateral medulla was stained with a voltage-sensitive dye (Di-2 ANEPEQ) centered within, and adjacent to, the pre-Bötzinger complex, as defined by anatomic landmarks and from extracellular recording of respiratory related discharge. During eupnea, fluorescence initially increased prior to the onset of phrenic nerve activity and progressively intensified with inspiration peaking at the end of inspiration. During early expiration, fluorescence declined slowly throughout this phase. In contrast, when the respiratory pattern was shifted to gasping, only inspiratory fluorescence signals were observed. Regions active during gasping showed more intense fluorescence and there was a recruitment of additional medullary regions that were not active during eupnea. Closer examination of regions of peak fluorescence during eupnea and gasping revealed that these areas were distinct spatially. These results suggest that the shift in respiratory motor pattern from eupnea to gasping is associated with changes in the spatiotemporal organization of the ventrolateral medullary respiratory network. NIH and BHF funded research

Efficacy of ketorolac in lieu of narcotics in the operative management of laparoscopic surgery for morbid obesity

Prompt recovery of protective airway reflexes, freedom from pain, ability to cooperate with respiratory physical therapy, early ambulation and discharge from the postanesthesia care unit (PACU), coupled with a stable intraoperative environment have been desired goals of anesthesia management of morbidly obese patients. We used ketorolac in lieu of narcotics toward this goal and present our subjective and objective data in this study. A total of 50 morbidly obese patients undergoing laparoscopic gastric bypass surgery were randomly assigned to 2 groups of 25 each. Group I received intravenous ketorolac perioperatively, which was continued 24 hours postoperatively. Group II received remifentanyl intraoperatively as a part of balanced anesthesia. Intraoperative hemodynamic stability was assessed based on blood pressure, pulse rate, and bispectral index score values. Postoperative pain intensity using a visual analogue scale, as well as the presence of nausea, vomiting, hypotension, or respiratory depression, were also recorded. Postoperative side effects, including pain, nausea, and vomiting; requirements for analgesics and antiemetic medications in the PACU; and the time spent in the PACU varied significantly between the 2 groups. Continued administration of ketorolac during the first 24 hours postoperatively led to improved patient satisfaction and more enthusiastic participation in respiratory physical therapy. Perioperative use of intravenous ketorolac up to 24 hours after laparoscopic gastric bypass surgery for morbid obesity helps provide a more stable intraoperative environment, earlier discharge from the PACU, and better outcome in this subset of patients.

Analysis of activity of motor units in the biceps brachii muscle after intercostal-musculocutaneous nerve transfer

We examined respiratory activity of motor units (MUs) in the internal intercostal nerves (IICNs)-transferred biceps brachii muscle (IC-biceps) in cats. MUs of IC-biceps showed respiratory discharges in inspiratory and expiratory phases, and these were enhanced by CO 2 inhalation. Narrowing the airway also enhanced inspiratory and expiratory MUs activity. A mechanical load to the thorax immediately enhanced inspiratory MUs activity and weakened expiratory MUs activity. We analyzed the cross-correlation of MUs activity in interchondral muscle and IC-biceps to characterize the respiratory spinal descending inputs to motoneurons. We confirmed the short-term synchronization from interchondral muscles indicating divergence of a single respiratory presynaptic axon to thoracic motoneurons, but could not find synchronization from IC-biceps. The motor axonal conduction velocity (axonal CV) of IC-biceps MUs was lower than that of interchondral muscles. There was no correlation between the respiratory recruitment order of IC-biceps MUs and their axonal CV. These results indicate that IC-biceps shows the respiratory activities and afferent inputs from intercostal muscle spindles in the neighboring segments remain influential on activity of IC-biceps. In addition, the short-term synchronization from IC-biceps could not be found, suggesting that the intercostal nerve transfer alters the respiratory spinal descending inputs to thoracic motoneurons.

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat

Opioids depress respiration and decrease chest wall compliance. A previous study in this laboratory showed that dopamine-D(1) receptor (D(1)R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D(1)R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 +/- 3.4 microg/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO(2)), elevated end-tidal carbon dioxide (ETCO(2)), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 microg/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D(1)R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO(2) and ETCO(2) to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 +/- 4.3 microg/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D(1)R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia.

Spinal anesthesia for diagnostic cardiac catheterization in high‐risk infants

The main goals of diagnostic cardiac catheterization (DCC) in infants are to evaluate the anatomy and physiology of congenital and acquired cardiac defects while maintaining normal respiratory and hemodynamic variables. The aims of anesthesia for infants undergoing DCC are to prevent pain and movement during the procedure. General anesthesia (GA) or deep sedation could have undesirable respiratory and hemodynamic effects for conducting such studies. Furthermore, GA is associated with increased risks, especially in high-risk infants. Spinal anesthesia (SA) is a successful alternative to GA in surgery on infants with a history of prematurity and respiratory problems, with minimal respiratory and hemodynamic changes. We studied whether those advantages were applicable to DCC, and used a predetermined SA protocol in a cohort of 12 infants with compromised respiratory status. Success rate, study completion, complications, hemodynamic and respiratory effects and recovery profile were recorded. Failure rate was significantly higher in infants older than 6 months. There was no significant difference between baseline and intraprocedure hemodynamic and respiratory parameters. The time to discharge was relatively short (33 +/- 12 min). Spinal anesthesia apparently provides stable hemodynamics and respiratory variables, rapid recovery and discharge time, and may be a viable alternative to GA or deep sedation in high-risk infants <6 months old undergoing DCC.

Effects of anesthetics on hypoglossal nerve discharge and c-Fos expression in brainstem hypoglossal premotor neurons.

This study examined the effects of anesthesia on the hypoglossal nerve and diaphragm activities and on c-Fos expression in brainstem hypoglossal premotor neurons (pmXII). Experiments were performed in 71 rats by using halothane inhalation, pentobarbital sodium, or mixtures of alpha-chloralose and urethane or ketamine and xylazine. First, various cardiorespiratory parameters were measured in the rats (n = 31) during both awake and anesthetized conditions. The volatile anesthetic halothane, but not the other anesthetics, was always associated with a strong phasic inspiratory activity in the hypoglossal nerve. Second, a double-immunohistochemical study was performed in awake and anesthetized rats (n = 40) to gauge the level of activity of pmXII neurons. Brainstem pmXII neurons were identified after microiontophoresis of the retrograde tracer Fluoro-Gold in the right hypoglossal motor nucleus. Patterns of c-Fos expression at different brainstem levels were compared in five groups of rats (i.e., awake or anesthetized with halothane, pentobarbital, chloralose-urethane, and ketamine-xylazine). Sections were processed for double detection of c-Fos protein and Fluoro-Gold by using the standard ABC method and a two-color peroxidase technique. Anesthesia with halothane induced the strongest c-Fos expression in a restricted pool of pmXII located in the pons at the level of the Kölliker-Fuse nucleus and the intertrigeminal region. The results demonstrated a major effect of halothane in inducing changes in hypoglossal activity and revealed a differential expression of c-Fos protein in pmXII neurons among groups of anesthetized rats. We suggest that halothane mediates changes in respiratory hypoglossal nerve discharge by altering activity of premotor neurons in the Kölliker-Fuse and intertrigeminal region.

Discharge patterns of preganglionic neurones with axons in a cardiac vagal branch in the rat.

The fibre types that run in a vagal branch projecting to the rat heart are described in this study. In order to obtain spontaneous discharge in this vagal branch and optimal recording conditions, we compared the decerebrate state to urethane, urethane-chloralose and pentobarbital-chloralose anaesthesia with regard to level of chronotropic cardiac vagal tone. Administration of atropine (2 mg kg(-1), I.V.) significantly decreased baseline cardiac interval only in the decerebrate and urethane-anaesthetised rat (by 0.018 +/- 0.001 s and 0.019 +/- 0.002 s, respectively). As a result of these experiments, urethane was chosen as the anaesthetic for all subsequent studies. Using a heart rate signal-averaging method we demonstrated that rat cardiac vagal preganglionic neurones innervating the sinoatrial node should have an expiratory discharge pattern, as reported in other species. However, only 5 % of chronotropic vagal tone was found to be subject to respiratory sinus arrhythmia. A suction microelectrode method, combined with spike-triggered averaging, was employed to record activity from a total of 58 vagal afferents that had axons in this branch. Approximately 75 % of these latter sensory fibres displayed cardiac rhythm. In a separate study we also recorded 318 preganglionic neurones with axons in the right cardiac vagal branch of the rat. Respiratory-modulated preganglionic units were statistically less common than tonically firing units. Six preganglionic subtypes were categorised according to conduction velocity and respiratory discharge pattern. Myelinated B-fibre and unmyelinated C-fibre types were found to be equally prevalent and equally likely to be reflexly excited during the pulmonary chemoreflex and the peripheral arterial chemoreflexes. The electrophysiological analysis has shown how diverse the discharge patterns of the preganglionic neurones or interneurones are whose axons course in the right cardiac vagal branch of the rat. The results of these experiments demonstrate the usefulness of combining spike discrimination with multiple spike-triggered averaging to simultaneously record B and C centrifugal vagal efferents.

Ontogeny of the Pre-Bötzinger Complex in Perinatal Rats

The aim of this study was to provide a systematic examination of the ontogenesis of the mammalian respiratory rhythm generating center, the pre-Bötzinger complex (pre-BötC). A combination of immunohistochemical markers and electrophysiological recordings was used to determine the time of inception of the pre-BötC and the developmental changes during the perinatal period in rats spanning from embryonic day 15 (E15) to postnatal day 7. The first clear indication of neurons immunopositive for neurokinin-1 receptors (NK1Rs) and somatostatin expression, two proposed markers for pre-BötC neurons, was at approximately E17. Birth dating of neurons in the ventrolateral medulla using 5-bromo-2'-deoxyuridine demonstrated that NK1R-positive neurons populating the area of the pre-BötC during late E16-E18 are born at E12.5-E13.5, approximately 2 d later than adjacent NK1R-positive neurons in the ventrolateral medulla. Extracellular recordings of neuronal populations within the pre-BötC of perinatal medullary slice preparations demonstrated that the onset of rhythmical respiratory discharge commences at approximately E17. Application of substance P, a ligand for NK1R receptors, to the media bathing E17 medullary slice and brainstem-spinal cord preparations resulted in a marked increase in respiratory frequency. These data provide insights into the ontogeny of the pre-BötC, giving fundamental information on the genesis, settlement, and inception of rhythmic activity within the group of neurons proposed to be responsible for the respiratory rhythm generation. Furthermore, this provides the foundation for further analyses of cell lineage, the transcriptional control of respiratory neuronal development, and electrophysiological and pharmacological properties of the pre-BötC during the prenatal period.

Avian influenza (H9N2) outbreak in Iran.

An epidemic of avian influenza (AI) (H9N2) occurred in broiler chicken farms in Iran during 1998-01. Mortality between 20% and 60% was commonly observed on the affected farms. Mixed infections of the influenza virus with other respiratory pathogens, particularly infectious bronchitis virus and Mycoplasma gallisepticum, were thought to be responsible for such high mortality, which resulted in great economic losses. Clinical signs included swelling of the periorbital tissues and sinuses, typical respiratory discharge, and severe respiratory distress. Gross lesions included extensive hyperemia of the respiratory system followed by exudation and cast formation in the tracheal biforcation extending into the secondary bronchi. Light microscopy lesions were characterized by severe necrotizing tracheatis. Serological examination using H9N2 AI viral antigen produced inconsistent results. Ultrastructural findings showed typical viral replication through budding processes on cell membranes of the tracheal epithelium.

Biphasic effects of morphine on bulbar respiratory neuronal activities in decerebrate cats

To understand neuronal mechanisms underlying respiratory depression induced by morphine, membrane potential, input resistance and burst discharge in different types of respiratory neurons were recorded in decerebrate and vagotomized cats. Intravenous morphine (0.3–3.0 mg/kg) dose-dependently decreased the respiratory discharge in the phrenic and iliohypogastric nerves. The drug changed the respiratory frequency in a biphasic fashion, a transient increase (early phase) followed by a long-lasting decrease (late phase). During the early phase, the membrane was hyperpolarized throughout the respiratory cycle and the burst discharge was decreased in all types of respiratory neurons. During the late phase, the active phase depolarization and the inactive phase hyperpolarization were decreased, resulting in a decline of membrane potential fluctuations. Input resistance was decreased during the early phase and increased during the late phase. Iontophoresed (50–100 nA) morphine produced hyperpolarization of the membrane and a decrease in input resistance in respiratory neurons. This hyperpolarization remained unaltered after iontophoresed tetrodotoxin depressed the synaptic transmission. These effects of morphine were completely blocked by naloxone and β-funaltrexamine, but not by naltrindole. The present results suggest that morphine depresses the respiratory neuronal activity through two different mechanisms, both of which are mediated by μ receptors.

Does Adenoidectomy Prevent Recurrent Otitis in Young Children?

Otolaryngology| May 01 2003 Does Adenoidectomy Prevent Recurrent Otitis in Young Children? AAP Grand Rounds (2003) 9 (5): 56–57. https://doi.org/10.1542/gr.9-5-56 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Does Adenoidectomy Prevent Recurrent Otitis in Young Children?. AAP Grand Rounds May 2003; 9 (5): 56–57. https://doi.org/10.1542/gr.9-5-56 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: adenoidectomy, otitis Source: Mattila PS, Joki-Erkkila V, Kilpi T, et al. Prevention of otitis media by adenoidectomy in children younger than 2 years. Arch Otolaryngol Head Neck Surg. 2003;129:163–168. The authors from Helsinki University Central Hospital, Tampere University Hospital, and National Public Health Institute, Finland, conducted a prospective study comparing adenoidectomy and tympanostomy with tympanostomy alone in preventing acute otitis media (AOM) in children younger than 2 years of age. Participants were selected from 2,497 children enrolled in the Finnish Otitis Media Vaccine Trial.1 A diagnosis of AOM was made if there were signs of effusion and symptoms related to acute otitis. Signs of effusion included “a visually abnormal membrane…suggesting middle ear effusion.” Symptoms included fever, ear pain, signs of upper respiratory infection, irritability, diarrhea, vomiting, or discharge from the ear. A total of 306 children between ages 1 and 2 who had experienced recurrent AOM (defined as 3 to 5 episodes of AOM during the last 6 months or 4 to 6 episodes of AOM during the past 12 months) were randomized into 1 of 2 groups. One hundred sixty-two of the 306 children were randomized to undergo tympanostomy alone and 144 to undergo tympanostomy and adenoidectomy. Of the 306 children randomized, 137 agreed to participate in the trial. Sixty-three of the 137 children had been randomized to the tympanostomy alone group (39% of the 162 children initially randomized to be treated with tympanostomy alone). Five of these 63 children later received adenoidectomy (before follow-up ended at the age of 2 years) and were transferred to the tympanostomy and adenoidectomy group for analysis. Seventy-five of the 137 patients had been randomized to the tympanostomy and adenoidectomy group (51% of the 144 children initially randomized to have tympanostomy and adenoidectomy). The children were followed to the age of 2 years. Specimens of middle ear effusion for culture were obtained from tympanostomy tube drainage or myringotomy in children presenting with AOM. Outcome measures included overall rate of AOM and rates of AOM caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. A secondary outcome measure was the number of days of otorrhea. The comparison of the risk of AOM between the treatment groups was made by Cox proportional hazards model adjusted for pneumococcal vaccine status, sex, number of siblings, and preoperative number of AOM episodes. In the randomized group, the rate of overall AOM per person-year was 2.40 for the tympanostomy group and 2.05 for the tympanostomy with adenoidectomy group. The efficacy of concurrent adenoidectomy was 19% (95% CI, −14% to 43%). The reduction in overall rate of AOM was mainly due to reduction in the rate of pneumococcal AOM (58%; 95% CI, 16% to 79%). There was no statistically significant difference in the frequency of days with purulent ear discharge between the 2 groups. In the non-randomized group, the efficacy of concurrent adenoidectomy was 25% (95% CI, −13% to 50%). Although there was a trend in favor of beneficial effect of concurrent adenoidectomy, the... You do not currently have access to this content.

Histaminergic modulation of the intact respiratory network of adult mice.

Histaminergic modulation of neuronal activity in the respiratory network was investigated under normoxic and hypoxic conditions in the working heart-brainstem preparation of adult mice. Systemic application of histamine, as well as the H-1 and H-3 receptor agonists 6-[2-(4-imidazolyl)ethylamino]- N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT) and imetit, 0.5-10 micro M, significantly increased the frequency of respiratory burst discharges. Dimaprit, an H-2 receptor agonist, had no effect on respiratory activity. To test for ongoing histaminergic modulation we applied the histamine receptor antagonists pyrilamine (H-1); cimetidine (H-2) and thioperamide (H-3), each 0.5-10 micro M. Only the H-1 receptor antagonist had significant effects, viz. reduction of respiratory frequency and depression of burst amplitude. Underlying effects of histamine receptor activation were identified at the cellular level. Intracellular recordings showed that histamine mediated an increase in synaptic drive potentials in inspiratory neurones while augmentation of inhibitory and excitatory synaptic activity was observed in expiratory neurones. The augmented synaptic depolarisation of inspiratory neurones was blocked by the H-1 receptor antagonist. Histaminergic modulation is also involved in the hypoxic response of the respiratory network. Blockade of H-1 receptors significantly attenuated secondary depression of the biphasic hypoxic responses, while hypoxic augmentation was not affected. We conclude that histamine is a functional neuromodulator, which is tonically active in the respiratory network and is activated further during hypoxia. The data indicate that histaminergic neuromodulation acts predominantly via H-1 receptors.

Regeneration of acutely and chronically injured descending respiratory pathways within post-traumatic nerve grafts

Central respiratory neurons, which are acutely axotomized by peripheral nerve grafts implanted at the level of the descending respiratory pathways within the C2 spinal cord, can regenerate their axons within the grafts and still transmit normal physiological messages [Decherchi et al., 1996. Exp. Neurol. 137, 1–14]. The present work investigated the extent to which mature central neurons, acutely or chronically axotomized by a spinal lesion, still maintain the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures and remained functional. This study is an extension of earlier work employing the more chronic lesions, that investigated whether respiratory neurons chronically axotomized by a spinal cord injury can retain the ability to regenerate their axonal process within a post-traumatic peripheral nerve graft. Here implantation was performed into the supra-lesional ventrolateral part of the ipsilateral C2 spinal cord (at the level of the descending respiratory pathways) previously hemisected at the C3 level. In the present study, these post-traumatic peripheral nerve grafts were performed either acutely (group I, n=15, 2.5 h post-injury: acute conditions) or chronically (group II, n=17, 3 weeks; group III, n=6, 3 months: chronic conditions) after the injury. Electrophysiological recording of teased filaments ( n=2362) within the post-traumatic peripheral nerve grafts revealed the presence of regenerated nerve fibers with spontaneous unitary impulse traffic (graft units, n=954) in all animals. These graft units were respiratory ( n=247) and non-respiratory ( n=707). Respiratory discharges originated from central respiratory neurons which remained functional with preserved afferent connections. Except for the group III, post-traumatic C2 peripheral nerve grafts of the groups I and II contained a significantly higher occurrence rate (13.2±2% and 11.6±1.9%) of respiratory units than C2 spinal peripheral nerve grafts (5.9±1.6%) realized without previous CNS injury. The main conclusion of our study is that for a prolonged period of 3 weeks following a spinal cord injury, central respiratory neurons have the potential to remain functional and to regenerate their axonal process within post-traumatic peripheral nerve grafts inserted rostrally to the spinal damage. This indicates that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. This suggests that surgical intervention which is not always possible immediately after a spinal cord injury may be satisfactorily carried out after an appropriate delay.

Development of the rat respiratory neuron network during the late fetal period

We studied developmental changes in respiratory-like C4 activity and respiratory-related neurons in the ventrolateral medulla (VLM) of brainstem-spinal cord preparations from rat fetuses after embryonic day 16 (E16). In addition to respiratory nerve activity, non-respiratory activity was recorded from the C4 ventral root of preparations before E19. The burst duration of respiratory nerve discharge increased markedly at E19/20. Subtypes of neurons similar to newborn respiratory neurons were found in preparations with prolonged burst duration (more than 400 ms) after E20. These subtypes were not evident in preparations with short burst duration (less than 300 ms) before E19. About 60% of the inspiratory neurons in E17-19 preparations produced voltage-dependent burst activity, which was preserved in low Ca(2+)/high Mg(2+) synaptic blockade solution. In about 11% of the inspiratory neurons of E18-19 preparations, activation of one neuron induced activation of the inspiratory neuron network and generation of a full C4 inspiratory burst. The present findings suggest that respiratory neuron networks mature functionally to the level of the neonatal respiratory neuron networks during gestation period E19/20. Potentiation of synaptic interaction between respiratory neurons, causing developmental changes in the burst pattern, might be involved in the maturation process during late fetal stages.

Monoaminergic neurons, chemosensation and arousal

In recent years, immense progress has been made in understanding central chemosensitivity at the cellular and functional levels. Combining molecular biological techniques (early gene expression as an index of cell activation) with neurotransmitter immunohistochemistry, new information has been generated related to neurochemical coding in chemosensory cells. We found that CO 2 exposure leads to activation of discrete cell groups along the neuraxis, including subsets of cells belonging to monoaminergic cells, noradrenaline-, serotonin-, and histamine-containing neurons. In part, they may play a modulatory role in the respiratory response to hypercapnia that could be related to their behavioral state control function. Activation of monoaminergic neurons by an increase in CO 2/H + could facilitate respiratory related motor discharge, particularly activity of upper airway dilating muscles. In addition, these neurons coordinate sympathetic and parasympathetic tone to visceral organs, and participate in adjustments of blood flow with the level of motor activity. Any deficit in CO 2 chemosensitivity of a network composed of inter-related monoaminergic nuclei might lead to disfacilitation of motor outputs and to failure of neuroendocrine and homeostatic responses to life-threatening challenges (e.g. asphyxia) during sleep.

Differential modulation of respiratory neuronal discharge patterns by GABA(A) receptor and apamin-sensitive K(+) channel antagonism.

The discharge patterns of respiratory neurons of the caudal ventral respiratory group (cVRG) appear to be subject to potent GABAergic gain modulation. Local application of the GABA(A) receptor antagonist bicuculline methochloride amplifies the underlying discharge frequency (F(n)) patterns mediated by endogenous excitatory and inhibitory synaptic inputs. Gain modulation can also be produced by alterations in the amplitude of spike afterhyperpolarizations (AHPs) mediated by apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK) channels. Since methyl derivatives of bicuculline (BICm) also have been shown to reduce the amplitude of AHPs, in vitro, it is possible that the BICm-induced gain modulation is due to a block of SK channels. The purpose of these studies was to determine the mechanisms by which BICm produces gain modulation and to characterize the influence of SK channels in the control of respiratory neuron discharge. Six protocols were used in this in vivo study of cVRG inspiratory (I) and expiratory (E) neurons in decerebrate, paralyzed, ventilated dogs. The protocols included characterizations of the neuronal responses to 1) BICm and apamin on the same neuron, 2) BICm during maximum apamin-induced block of AHPs, 3) apamin during maximum BICm-induced gain modulatory responses, 4) the specific GABA(A) receptor antagonist, (+)beta-hydrastine, 5) the specific GABA(A) receptor agonist, muscimol, and 6) the GABA uptake inhibitor, nipecotic acid. For protocols 3, 5, and 6, only E neurons were studied. Four-barrel micropipettes were used for extracellular single neuron recording and pressure ejection of drugs. Cycle-triggered histograms were used to quantify the F(n) patterns and to determine the drug-induced changes in the gain (slope) and offset of the F(n) patterns. Compared to apamin at maximum effective dose rates, BICm produced a 2.1-fold greater increase in peak F(n) and a 3.1-fold greater increase in average F(n). BICm and apamin produced similar increases in gain, but the offsets due to apamin were more negative. The responses to hydrastine were similar to BICm. During maximum apamin block, BICm produced an additional 112 +/- 22% increase in peak F(n). Conversely, apamin produced an additional 176 +/- 74% increase in peak F(n) during the maximum BICm-induced response. Muscimol and nipecotic acid both decreased the gain and offset of the discharge patterns. Taken together, these results suggest that the gain modulatory effect of BICm is due to a reduction of GABA(A)-ergic shunting inhibition rather than a reduction in AHPs by block of SK channels in canine cVRG neurons.

Incidence of pneumothorax from intercostal nerve block for analgesia in rib fractures.

The incidence of pneumothorax (PTX) after individual intercostal nerve block (INB) for postoperative pain reportedly varies from 0.073% to 19%.1-3 This study investigated the incidence of PTX after INB for rib fractures. We conducted a retrospective chart review of patients admitted between January 1996 and December 1999 with rib fractures who received INB. One hundred sixty-one patients received 249 intercostal nerve block procedures (INBPs). An INBP is one session where a set of intercostal nerves are blocked. A total of 1,020 individual intercostal nerves were blocked. There were 14 pneumothoraces. The overall incidence of PTX per patient was 8.7%, with an incidence of PTX per INBP of 5.6%. The incidence of PTX was 1.4% for each individual intercostal nerve blocked. The incidence of PTX per individual intercostal nerve blocked is low. INB is an effective form of analgesia, and for most patients with rib fractures one INBP is sufficient to allow adequate respiratory exercises and discharge from the hospital.