Evaluation of postoperative pain in patients undergoing modified radical mastectomy with pectoralis or serratus-intercostal fascial plane blocks.

BACKGROUND: Regional nerve blocks are an integral part of multimodal analgesia and should be chosen based on their efficacy, convenience, and minimal side effects. Here, we compare the use of pectoral (PEC II) and serratus-intercostal fascial plane (SIFP) blocks in breast carcinoma cases undergoing modified radical mastectomy (MRM) in terms of the postoperative analgesic efficacy and shoulder mobility. METHODS: The primary outcome of this prospective controlled study was to compare the postoperative static and dynamic pain scores, and the secondary outcome was to assess the shoulder pain, range of shoulder joint motion, and hemodynamic parameters. Sixty patients were randomly allocated to three groups and given general anesthesia. All patients received paracetamol, diclofenac, and rescue doses of tramadol based on the Institute's Acute Pain Service (APS) policy. No block was performed in group C (control), whereas groups P and S received PEC II and SIFP blocks, respectively, before surgical incision. RESULTS: The groups were comparable in terms of age, weight, height, and body mass index distribution (P > 0.05). Dynamic pain relief was significantly better 12 and 24 h postoperatively in groups P (P = 0.034 and P = 0.04, respectively) and S (P = 0.01 and P = 0.02, respectively) compared to group C. Shoulder pain relief and shoulder mobility were better in group S, while the hemodynamic parameters were more stable in group P. CONCLUSIONS: Both SIFP and PEC blocks have comparable dynamic and static pain relief with better shoulder pain scores in patients receiving SIFP.

Rhomboid Intercostal and Subserratus Plane Block: A Cadaveric and Clinical Evaluation.

BACKGROUND AND OBJECTIVES: Fascial plane blocks are rapidly emerging to provide safe, feasible alternatives to epidural analgesia for thoracic and abdominal pain. We define a new option for chest wall and upper abdominal analgesia, termed the rhomboid intercostal and subserratus plane (RISS) block. The RISS tissue plane extends deep to the erector spinae muscle medially and deep to the serratus anterior muscle laterally. We describe a 2-part proof-of-concept study to validate the RISS block, including a cadaveric study to evaluate injectate spread and a retrospective case series to assess dermatomal coverage and analgesic efficacy. METHODS: For the cadaveric portion of the study, bilateral ultrasound-guided RISS blocks were performed on 6 fresh cadavers with 30 mL of 0.5% methylcellulose with india ink. For the retrospective case series, we present 15 patients who underwent RISS block or RISS catheter insertion for heterogeneous indications including abdominal surgery, rib fractures, chest tube-associated pain, or postoperative incisional chest wall pain. RESULTS: In the cadaveric specimens, we identified staining of the lateral branches of the intercostal nerves from T3 to T9 reaching the posterior primary rami deep to the erector spinae muscle medially. In the clinical case series, dermatomal coverage was observed in the anterior hemithorax with visual analog pain scores less than 5 in patients who underwent both single-shot and continuous catheter infusions. CONCLUSIONS: Our preliminary cadaveric and clinical data suggest that RISS block anesthetizes the lateral cutaneous branches of the thoracic intercostal nerves and can be used in multiple clinical settings for chest wall and upper abdominal analgesia.

Parasternal intercostal muscle activity during methacholine-induced bronchoconstriction.

NEW FINDINGS: What is the central question of this study? The parasternal intercostal electromyogram (EMGpara) is known to provide an accurate, non-invasive index of respiratory load-capacity balance. Although relationships between EMGpara and both airflow obstruction and hyperinflation have been shown, the independent contribution of each factor has not been examined. What is the main finding and its importance? Reductions in airway calibre and inspiratory capacity along with increases in EMGpara were induced via methacholine challenge. A strong inverse relationship was observed between EMGpara and airway obstruction, with no influence of inspiratory capacity. These data suggest that EMGpara is more strongly influenced by airway calibre than by changes in end-expiratory lung volume during airway challenge testing. Neural respiratory drive, measured via the parasternal intercostal electromyogram (EMGpara), provides a non-invasive index of the load-capacity balance of the respiratory muscle pump. Previous studies in patients with obstructive lung disease have shown strong relationships between EMGpara and the extent of both airflow obstruction and hyperinflation. The relative influence of the two factors has not, however, been described. Airflow obstruction was induced via methacholine challenge testing in 25 adult humans. Forced expiratory volume in 1 s (FEV1 ) and surface EMGpara during tidal breathing were measured after each dose, with 20 of the participants also undergoing measurements of inspiratory capacity (IC) at each stage. Linear mixed model analysis was used to assess dose-wise changes in FEV1 and EMGpara, and thereafter to determine the influence of changes in FEV1 and IC on change in EMGpara. Median (interquartile range) FEV1 decreased significantly [from 96.00 (80.00-122.30) to 67.80 (37.98-92.27)% predicted, P < 0.0001] and EMGpara increased significantly [from 5.37 (2.25-8.92) to 6.27 (3.37-19.60) µV, P < 0.0001] from baseline to end of test. Linear mixed model analysis showed a significant interaction between methacholine dose and induced change in EMGpara, with an increase in EMGpara of 0.24 (95% confidence interval 0.11-0.37) µV per methacholine dose2 . Change in FEV1 further influenced this relationship [increase in slope of 0.002 (0.004-0.001) µV dose-2 per % predicted fall in FEV1 , P = 0.011], but not with change in IC. These data suggest that bronchoconstriction exerts a more potent influence on levels of EMGpara than changes in end-expiratory lung volume during methacholine challenge.

Embolization biomaterial reinforced with nanotechnology for an in-situ release of anti-angiogenic agent in the treatment of hyper-vascularized tumors and arteriovenous malformations.

A polymer based material was developed to act as an embolic agent and drug reservoir for the treatment of arteriovenous malformations (AVM) and hyper vascularized solid tumors. The aim was to combine the blocking of blood supply to the target region and the inhibition of the embolization-stimulated angiogenesis. The material is composed of an ethanolic solution of a linear acrylate based copolymer and acrylate calibrated microparticles containing nanospheres loaded with sunitinib, an anti-angiogenic agent. The precipitation of the linear copolymer in aqueous environment after injection through microcatheter results in the formation of an in-situ embolization gel whereas the microparticles serve to increase the cohesive properties of the embolization agent and to form a reservoir from which the sunitinib-loaded nanospheres are released post-embolization. The swollen state of the microparticles in contact with aqueous medium results in the release of the nanospheres out of microparticles macromolecular structure. After the synthesis, the formulation and the characterization of the different components of the material, anti-angiogenic activity was evaluated in vitro using endothelial cells and in vivo using corneal neovascularization model in rabbit. The efficiency of the arterial embolization was tested in vivo in a sheep model. Results proved the feasibility of this new system for vascular embolization in association with an in situ delivery of anti-angiogenic drug. This combination is a promising strategy for the management of arteriovenous malformations and solid tumors.

Aminophylline increases respiratory muscle activity during hypercapnia in humans.

BACKGROUND: Theophylline is an old drug traditionally used as a bronchodilator, although it was recently shown to possess anti-inflammatory properties, enhance the actions of corticosteroid actions, and stimulate the respiratory neuronal network. Theophylline has been recognized as an important drug for not only asthma but also corticosteroid-insensitive chronic obstructive pulmonary disease (COPD). To clarify the role of theophylline in hypercapnic ventilatory responses in humans, we analyzed the effects of aminophylline administered at the usual clinical therapeutic doses on ventilation and augmentation of respiratory muscle contractility in room air and under 3 conditions of hypercapnia. STUDY DESIGN: We performed electromyography (EMG) of the parasternal intercostal muscle (PARA) and transversus abdominis muscle (TA) in 7 healthy subjects and recorded both ventilatory parameters and EMG data in room air and under 3 conditions of hypercapnia before (control) and during aminophylline administration. RESULTS: Before aminophylline administration (control), hypercapnic stimulation elicited ventilatory augmentation in a hypercapnia intensity-dependent manner. Ventilatory parameters (tidal volume, frequency of respiration, and minute ventilation) showed significant increases from lower PaCO2 levels during aminophylline administration when compared with the corresponding values before aminophylline administration. EMG activity of both PARA and TA increased significantly at each level of hypercapnia, and those augmentations were shown from lower PaCO2 levels during aminophylline administration. CONCLUSION: Aminophylline administered at the usual clinical therapeutic dose increases ventilation and EMG activity of both inspiratory and expiratory muscles during hypercapnia in healthy humans.

[Respiratory responses to microinjections of gastrin-releasing peptide into the solitary tract nucleus].

In acute experiments on urethane-anesthetized rats, the respiratory effects ofmicroinjections of 10(-5), 10(-8) and 10(-10) M gastrin-releasing peptide (GRP) into the solitary tract nucleus were investigated. It was found that microinjections of the neuropeptide induced an increase in tidal volume, amplitude of diaphragm and external intercostal muscles firing activity and in expiratory duration. The most obvious respiratory responses observed when 10(-8) M GRP was used, while 10(-10) M GRP appeared to be sub-threshold and didn't alter the breathing pattern and activity of inspiratory muscles. In some experiments, where the blood pressure and the heart rate was monitored alone with breathing pattern, these parameters did not change after GRP microinjections into the solitary tract nucleus. The obtained data together with particularities of the distribution of GRP receptors in the brainstem suggest the possibility of GRP involvement into the respiratory control mechanisms at the level of solitary tract nucleus.

Restoration of soman-blocked neuromuscular transmission in human and rat muscle by the bispyridinium non-oxime MB327 in vitro.

The standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes is not sufficiently effective against all types of nerve agents. Alternative therapeutic strategies are required and bispyridinium non-oximes, acting as nicotinic antagonists, were identified as promising compounds. A previous study showed that the di(methanesulfonate) salt of the bispyridinium compound MB327 could restore soman-impaired neuromuscular function in vitro and improve survival of sarin, soman and tabun poisoned guinea pigs in vivo. Here, by using the indirect field stimulation technique, the ability of MB327 to counteract soman-impaired neuromuscular transmission was investigated in human intercostal muscle and rat diaphragm preparations. MB327 restored muscle force in a concentration-dependent manner in both species without reactivating soman-inhibited acetylcholinesterase. The therapeutic effect of MB327 could be washed out, indicating a direct effect at the nicotinic receptor level. Also the ability of MB327 to restore respiratory muscle function could be demonstrated for the first time in rat and human tissue. In combination with previous in vitro and in vivo findings MB327 may be considered a promising compound for the treatment of nerve agent poisoning and further studies are needed to identify optimized drug combinations, concentrations and dosing intervals to provide an effective therapy for OP poisoning.

Restoration of nerve agent inhibited muscle force production in human intercostal muscle strips with HI 6.

An important factor for successful therapy of poisoning with organophosphorus compounds (OP) is the rapid restoration of blocked respiratory muscle function. To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Unfortunately, clinically used oximes, e.g. obidoxime and pralidoxime, are of limited effectiveness in poisoning with different OP nerve agents requiring the search for alternative oximes, e.g. HI 6. In view of substantial species differences regarding reactivation properties of oximes, the effect of HI 6 was investigated with sarin, tabun and soman exposed human intercostal muscle. Muscle force production by indirect field stimulation and the activity of the human muscle AChE was assessed. 30 µM HI 6 resulted in an almost complete recovery of sarin blocked muscle force and in an increase of completely inhibited muscle AChE activity to approx. 30% of control. In soman or tabun exposed human intercostal muscle HI 6 (50 and 100 µM) had no effect on blocked muscle force or on inhibited human muscle AChE activity. In addition, HI 6 up to 1000 µM had no effect on soman blocked muscle force indicating that this oxime has no direct, pharmacological effect in human tissue. These results emphasize that sufficient reactivation of AChE is necessary for a beneficial therapeutic effect on nerve agent blocked neuromuscular transmission.

Pre- and post-treatment effect of physostigmine on soman-inhibited human erythrocyte and muscle acetylcholinesterase in vitro.

Standard treatment of organophosphorus (OP) poisoning includes administration of an antimuscarinic (e.g., atropine) and of an oxime-based reactivator. However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Hence, the inability of standard treatment procedures to counteract the effects of soman poisoning resulted in the search for alternative strategies. Recently, results of an in vivo guinea pig study indicated a therapeutic effect of physostigmine given after soman. The present study was performed to investigate a possible pre- and post-treatment effect of physostigmine on soman-inhibited human AChE given at different time intervals before or after perfusion with soman by using a well-established dynamically working in vitro model for real-time analysis of erythrocyte and muscle AChE. The major findings were that prophylactic physostigmine prevented complete inhibition of AChE by soman and resulted in partial spontaneous recovery of the enzyme by de-carbamylation. Physostigmine given as post-treatment resulted in a time-dependent reduction of the protection from soman inhibition and recovery of AChE. Hence, these date indicate that physostigmine given after soman does not protect AChE from irreversible inhibition by the OP and that the observed therapeutic effect of physostigmine in nerve agent poisoning in vivo is probably due to other factors.

Protection of human muscle acetylcholinesterase from soman by pyridostigmine bromide.

INTRODUCTION: Pretreatment with pyridostigmine bromide (PB) of human intercostal muscle fibers exposed to the irreversible acetylcholinesterase (AChE) inhibitor soman was investigated. METHODS: Muscles were pretreated with 3 × 10(-6) M PB or saline for 20 minutes, then exposed to 10(-7) M soman for 10 minutes. RESULTS: AChE of muscles treated with soman alone was inhibited >95%. In contrast, PB pretreatment of soman-exposed bundles protected 20% of AChE activity. AChE of bundles exposed to PB alone recovered after 4 hours, but bundles exposed to both PB and soman did not. Soman-induced reduction of resting membrane potentials and increment of amplitudes and decay times of miniature endplate potentials (MEPPs) were partially corrected by PB pretreatment. CONCLUSIONS: In vitro pretreatment of human muscles with PB protected up to 20% of muscle AChE and ameliorated some deleterious effects on endplate physiology induced by soman.

[Massive iatrogenic haemothorax treated by lidocaïne-adrenaline intercostal injection]. / Hémothorax iatrogène massif jugulé par injection intercostale de lidocaïne-adrénaline.

INTRODUCTION: Massive haemothorax is a relatively rare complication of thoracocentesis or the placement of tube thoracostomy. It is principally caused by intercostal vessel injury. The therapeutic approach consists in pleural drainage and sometimes thoracotomy for haemostasis. CASE REPORT: We describe a frail 72 year old patient, who developed a massive haemothorax occurring after a tube thoracostomy placing, persisting despite second pleural drainage, and complicated by deep haemodynamic shock. He was considered to have a very high risk of mortality if surgery was undertaken. Haemorrhage was totally stopped after intercostal instillation of lidocaïne-adrenaline. CONCLUSION: This case report suggests a role for pleural vasoconstrictor injection as initial treatment in case of persistent pleural haemorrhage caused by intercostal vessel injury.

Menin expression modulates mesenchymal cell commitment to the myogenic and osteogenic lineages.

Menin plays an established role in the differentiation of mesenchymal cells to the osteogenic lineage. Conversely, whether Menin influences the commitment of mesenschymal cells to the myogenic lineage, despite expression in the developing somite was previously unclear. We observed that Menin is down-regulated in C2C12 and C3H10T1/2 mesenchymal cells when muscle differentiation is induced. Moreover, maintenance of Menin expression by constitutive ectopic expression inhibited muscle cell differentiation. Reduction of Menin expression by siRNA technology results in precocious muscle differentiation and concomitantly attenuates BMP-2 induced osteogenesis. Reduced Menin expression antagonizes BMP-2 and TGF-beta1 mediated inhibition of myogenesis. Furthermore, Menin was found to directly interact with and potentiate the transactivation properties of Smad3 in response to TGF-beta1. Finally in concert with these observations, tissue-specific inactivation of Men1 in Pax3-expressing somite precursor cells leads to a patterning defect of rib formation and increased muscle mass in the intercostal region. These data invoke a pivotal role for Menin in the competence of mesenchymal cells to respond to TGF-beta1 and BMP-2 signals. Thus, by modulating cytokine responsiveness Menin functions to alter the balance of multipotent mesenchymal cell commitment to the osteogenic or myogenic lineages.

Different sensitivity of miniature endplate currents in rat external and internal intercostal muscles to the acetylcholinesterase inhibitor C-547 as compared with diaphragm and extensor digitorum longus.

Derivative of 6-methyluracil, selective cholinesterase inhibitor C-547 potentiates miniature endplate currents (MEPCs) in rat external intercostal muscles (external ICM) more effectively than in internal intercostal muscles (internal ICM). Effect of the C-547 on intercostal muscles was compared with those on extensor digitorum longus (EDL) and diaphragm muscles. Half-effective concentrations for tau of MEPC decay arranged in increasing order were as follows: EDL, locomotor muscle, most sensitive = 1.3 nM, external ICM, inspiration muscle = 6.8 nM, diaphragm, main inspiration muscle = 28 nM, internal ICM, expiration muscle = 71 nM. External ICM might therefore be inhibited, similarly as the limb muscles, by nanomolar concentrations of the drug and do not participate in inspiration in the presence of the C-547. Moreover, internal ICM inhibition can hinder the expiration during exercise-induced fast breathing of C-547- treated experimental animals.

[Activation of satellite cells in the intercostal muscles of patients with chronic obstructive pulmonary disease]. / Activación de células satélite en el músculo intercostal de pacientes con EPOC.

OBJECTIVE: The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration. PATIENTS AND METHODS: The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype. RESULTS: The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] microm(2); P< .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; P>.05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; P< .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; P=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (P< .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (P=.05). CONCLUSIONS: The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.

Aminophylline increases parasternal intercostal muscle activity during hypoxia in humans.

To clarify the mechanism of action of aminophylline on the hypoxic ventilatory response in humans, we analyzed the effects of aminophylline on respiratory neural output. To evaluate the respiratory neural output, we analyzed the electromyogram (EMG) of the parasternal intercostal muscle, one of the major inspiratory muscles, in eight healthy subjects. Both before and during aminophylline administration, measurements of ventilatory parameters with EMG recordings were conducted in room air, mild hypoxia (F(I)(o)(2) 0.15), and severe hypoxia (F(I)(o)(2) 0.11). Before administering aminophylline, hypoxic stimulation elicited ventilatory augmentation in a hypoxia-intensity dependent manner. Administration of aminophylline caused significant increases in ventilation (V (I)), tidal volume (V(T)), respiratory frequency (f(R)), and the respiration-related phasic moving averaged EMG amplitude (tidal EMG), at corresponding levels of hypoxia compared to before aminophylline. Augmentation patterns of hypoxia-induced increases in V(T) and tidal EMG showed close similarity. These results indicate that augmentation of hypoxic ventilatory response by aminophylline is mainly mediated by an increase in the respiratory neural drive in healthy humans.

Histamine induced airway response in pre-school children assessed by a non-invasive EMG technique.

The aim of the study was to investigate the association between surface electromyographic (EMG) activity of the diaphragm and intercostal muscles, and clinical symptoms (wheeze, cough, increased respiratory rate and prolonged expiration) during bronchial challenge testing and after administration of salbutamol in asthmatic pre-school children. A histamine challenge test was performed in 20 asthmatic pre-school children. The histamine dose at the appearance of 1 or more clinical symptoms was defined as the maximum histamine provocation dose (PDcs). The clinical symptoms were recorded with a microphone over the trachea. The logarithm of the EMG-Activity-Ratio (log EMGAR; mean peak activity ratio to baseline of respiratory muscles during tidal breathing) was used as EMG parameter. In both the diaphragmatic and the intercostal log EMGAR values a linear increase was observed in the four histamine dose-steps prior to PDcs. At PDcs the mean log EMGAR of the diaphragm (di) and intercostal muscles (int) was significantly increased as compared to the baseline values. After administration of salbutamol the log EMGARdi and log EMGARint returned to baseline values and the clinical symptoms normalized in all children. At PDcs, no significant differences in the log EMGAR values could be detected at the appearance of the distinctive clinical symptoms, which suggests that wheezing is not the only indicator for the detection of airway responsiveness in young children. We found a linear association between histamine dose and the increase in surface diaphragmatic and intercostal respiratory EMG activity during a bronchial challenge test in pre-school asthmatic children, which returned to baseline values after inhalation of salbutamol. These findings support the idea that EMG measurements of the diaphragm and intercostal muscles may offer an opportunity to estimate airway response in young children in an alternative way.

GABAA and glycine receptors in regulation of intercostal and abdominal expiratory activity in vitro in neonatal rat.

The roles played by GABAA and glycine receptors in inspiratory-expiratory motor co-ordination and in tonic inhibitory regulation of expiratory motor activity were studied using brainstem-spinal cord (-rib) preparations from neonatal rats. Inspiratory activity was recorded from the C4 ventral root. Expiratory activity in internal intercostal muscle, internal oblique muscle or T13 ventral root was evoked by a decrease in perfusate pH from 7.4 to 7.1 (i.e. from normal to low pH conditions) and was limited to the first part of the expiratory phase. Under low pH conditions, bath application of 10 microM bicuculline, a GABAA receptor antagonist, caused the inspiratory burst to overlap the expiratory burst in 2/7 preparations. Overlapping of the expiratory burst with the inspiratory burst was observed in 7/7 preparations made under 10 microM bicuculline. Furthermore, such preparations exhibited expiratory bursts under bicuculline-containing normal pH conditions. Local application of 10 microM bicuculline to the brainstem under normal pH conditions evoked expiratory bursts, some of which overlapped the inspiratory bursts. Picrotoxin, another antagonist of the GABAA receptor, had similar effects. Under normal pH conditions, application of strychnine (0.2- 2.0 microM; a glycine receptor antagonist) to the brainstem did not evoke expiratory bursts. On subsequent application of strychnine-containing low pH solution, expiratory bursts were evoked and some (0.5 microM) or all (2.0 microM) of these overlapped the inspiratory burst. Simultaneous application of picrotoxin and strychnine to the brainstem evoked expiratory bursts that overlapped the inspiratory bursts and a subsequent decrease in perfusate pH to 7.1 increased the frequency of the respiratory rhythm. It was a characteristic finding that the duration of the expiratory burst exceeded that of the inspiratory burst under control low pH conditions. This remained true during concurrent blockade of GABAA and glycine receptors. The results suggest that in the in vitro preparation from neonatal rats: (1) GABAA and glycine receptors within the brainstem play important roles in the co-ordination between inspiratory and expiratory motor activity, (2) tonic inhibition via GABAA receptors, but not glycine receptors, plays a role in the regulation of expiratory motor activity and (3) inspiratory and expiratory burst termination is independent of both GABAA and glycine receptors.

Effect of pulmonary stretch receptor feedback and CO(2) on upper airway and respiratory pump muscle activity in the rat.

1. Our purpose was to examine the effects of chemoreceptor stimulation and lung inflation on neural drive to tongue protrudor and retractor muscles in the rat. 2. Inspiratory flow, tidal volume, transpulmonary pressure, compliance and electromyographic (EMG) activity of genioglossus (GG), hyoglossus (HG) and inspiratory intercostal (IIC) muscles were studied in 11 anaesthetized, tracheotomized and spontaneously breathing rats. Mean EMG activity during inspiration was compared with mean EMG activity during an occluded inspiration, at each of five levels of inspired CO(2) (0, 3, 6, 9 and 12 %). 3. Lung inflation suppressed EMG activity in all muscles, with the effect on both tongue muscles exceeding that of the intercostal muscles. Static elevations of end-expiratory lung volume evoked by 2 cmH(2)O positive end-expiratory pressure (PEEP) had no effect on tongue muscle activity. 4. Despite increasing inspiratory flow, tidal volume and transpulmonary pressure, the inhibition of tongue muscle activity by lung inflation diminished as arterial PCO2 (P(a),CO(2)) increased. 5. The onset of tongue muscle activity relative to the onset of IIC muscle activity advanced with increases in P(a),CO(2) but was unaffected by lung inflation. This suggests that hypoglossal and external intercostal motoneuron pools are controlled by different circuits or have different sensitivities to CO(2), lung inflation and/or anaesthetic agents. 6. We conclude that hypoglossal motoneuronal activity is more strongly influenced by chemoreceptor-mediated facilitation than by lung volume-mediated inhibition. Hypoglossal motoneurons driving tongue protrudor and retractor muscles respond identically to these stimuli.