Intercostal EMG Activity Research Articles

Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons.

Prolonged inhibition of respiratory neural activity elicits a long-lasting increase in phrenic nerve amplitude once respiratory neural activity is restored. Such long-lasting facilitation represents a form of respiratory motor plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although facilitation also occurs in inspiratory intercostal nerve activity after diminished respiratory neural activity (iIMF), it is of shorter duration. Atypical PKC activity in the cervical spinal cord is necessary for iPMF and iIMF, but the site and specific isoform of the relevant atypical PKC are unknown. Here, we used RNA interference to test the hypothesis that the zeta atypical PKC isoform (PKCζ) within phrenic motor neurons is necessary for iPMF but PKCζ within intercostal motor neurons is unnecessary for transient iIMF. Intrapleural injections of siRNAs targeting PKCζ (siPKCζ) to knock down PKCζ mRNA within phrenic and intercostal motor neurons were made in rats. Control rats received a nontargeting siRNA (NTsi) or an active siRNA pool targeting a novel PKC isoform, PKCθ (siPKCθ), which is required for other forms of respiratory motor plasticity. Phrenic nerve burst amplitude and external intercostal (T2) electromyographic (EMG) activity were measured in anesthetized and mechanically ventilated rats exposed to 30 min of respiratory neural inactivity (i.e., neural apnea) created by modest hypocapnia (20 min) or a similar recording duration without neural apnea (time control). Phrenic burst amplitude was increased in rats treated with NTsi (68 ± 10% baseline) and siPKCθ (57 ± 8% baseline) 60 min after neural apnea vs. time control rats (-3 ± 3% baseline), demonstrating iPMF. In contrast, intrapleural siPKCζ virtually abolished iPMF (5 ± 4% baseline). iIMF was transient in all groups exposed to neural apnea; however, intrapleural siPKCζ attenuated iIMF 5 min after neural apnea (50 ± 21% baseline) vs. NTsi (97 ± 22% baseline) and siPKCθ (103 ± 20% baseline). Neural inactivity elevated the phrenic, but not intercostal, responses to hypercapnia, an effect that was blocked by siPKCζ. We conclude that PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient iIMF.NEW & NOTEWORTHY We report important new findings concerning the mechanisms regulating a form of spinal neuroplasticity elicited by prolonged inhibition of respiratory neural activity, inactivity-induced phrenic motor facilitation (iPMF). We demonstrate that the atypical PKC isoform PKCζ within phrenic motor neurons is necessary for long-lasting iPMF, whereas intercostal motor neuron PKCζ contributes to, but is not necessary for, transient inspiratory intercostal facilitation. Our findings are novel and advance our understanding of mechanisms contributing to phrenic motor plasticity.

N‐Acetyl cysteine improves dystrophic (mdx) mouse diaphragm muscle quality and strength

Respiratory muscle weakness occurs as a consequence of dystrophin deficiency in Duchenne muscular dystrophy (DMD), with implications for breathing and airway protective behaviours. The mdx mouse model of DMD shows evidence of impaired respiratory muscle performance with attendant inflammation and oxidative stress. N‐Acetyl cysteine (NAC) is a dietary antioxidant commonly used in the treatment of respiratory disease. We sought to examine the effects of NAC intervention on respiratory system performance in the mdx mouse.Young adult male wild‐type and mdx mice were studied; a subset of mdx received 1% NAC in the drinking water for 14 days. Ventilation was assessed in conscious mice using whole‐body plethysmography. Inspiratory pressure and respiratory muscle (diaphragm and external intercostal) EMG activity were assessed in anaesthetised mice during ventilatory and non‐ventilatory behaviours. Diaphragm ex vivo force‐generating capacity, muscle structure, cytokine concentrations, glutathione status and mRNA expression were determined. Data were statistically compared by unpaired Student's t test.Diaphragm function was severely impaired in mdx, evidenced by reductions in force‐generating capacity (40–160Hz range), total muscle shortening and maximal shortening velocity compared to wild‐type. Extensive diaphragm myofibre remodelling and damage was observed for mdx, characterised by increased muscle fibrosis, immune cell filtration, muscle fibre central nucleation and embryonic myosin expression. The pro‐inflammatory cytokines IL‐1β and IL‐6 were elevated in mdx diaphragm and plasma samples. mRNA studies indicate an increase in gene expression related to muscle atrophy, regeneration and inflammation in mdx diaphragm, and a reduction in anti‐oxidant related gene expression. NAC supplementation increased mdx diaphragm force (60–160Hz), maximal shortening and shortening velocity. Collagen deposition and the infiltration of putative inflammatory cells in mdx diaphragm was decreased following NAC. Mdx diaphragm and plasma IL‐1β and IL‐6 concentrations were decreased following NAC. Glutathione reductase and peroxidase activities were increased in mdx diaphragm; both were unaffected by NAC. mRNA expression of Nrf2 was increased in mdx diaphragm and increased further with NAC supplementation. No adverse effects of NAC intervention were observed on ventilation, inspiratory pressure and EMG, and growth measures.We reveal that NAC treatment improved mdx diaphragm force‐generating capacity by way of beneficial anti‐inflammatory and anti‐fibrotic effects. These data support the potential use of NAC as an adjunctive therapy in the dystrophinopathies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Increased Bilateral External Intercostal EMG Activity during Tracheal Occlusions (TO) in Conscious Rats with Unilateral Cervical Spinal Cord Injury (c‐SCI)

Respiratory motor function after c‐SCI is often studied using anesthetized animal preparations with cervical spinal hemisection (C2HS). However, anesthesia can influence respiratory control, and conscious animal studies of chest wall external intercostal (EI) muscle function after C2HS are lacking. We hypothesized that TO in conscious rats would trigger bilateral recruitment of EI muscles as reflected by increased EMG activity 1 week after C2HS. Adult male Sprague Dawley rats were instrumented with wire EMG electrodes implanted bilaterally in the EI muscles and an inflatable vascular cuff around the extra‐thoracic trachea, 1 week prior to a left C2HS injury. TO trials were presented pre and 1 week post‐C2HS in conscious rats. Trachea was obstructed using cuff inflations for 3–5s followed by normal breathing for 10–15s. Data were collected for 2 min before (Pre‐TO), 20 min during (TO) and 2 min after (Post‐TO) TO trials. Pre‐TO integrated EI (intEI) EMG during eupneic breathing was significantly decreased bilaterally 1 week after C2HS. TO significantly increased bilateral intEI EMG, however, post‐TO intEI responses were variable. Conscious rats were able to significantly augment EI muscle EMG activity when presented with a TO 1 week post‐C2HS injury. Therefore, EI muscles play a significant role in maintenance of minute ventilation both during eupneic and loaded breathing 1 week after C2HS in conscious rats.

Effects of pharmacologic manipulation of the brainstem serotonergic system on duration of the laryngeal chemoreflex—implications for Sudden Infant Death Syndrome

Sudden infant death syndrome (SIDS) occurs when a sleeping infant fails to mount an effective response to a challenge to cardiorespiratory homeostasis. Serotonin receptor binding in the nucleus of the solitary tract (NTS) is reduced in infants who die of SIDS. The laryngeal chemoreflex (LCR) causes apnea and may initiate the process leading to SIDS. We tested the hypothesis that altering serotonergic signaling in the NTS would alter the duration of LCR apnea. Rat pups (P5 to P20) were anesthetized and tracheostomized. Tracheal tubing was inserted rostrally up to the larynx, and water was instilled to elicit the LCR. The EKG and intercostal EMG activity were recorded. ICV serotonin shortened apnea duration, and ICV WAY100635 (a 5HT‐1A receptor antagonist) prolonged it. ICV ketanserin (a 5HT‐2A receptor antagonist) had no consistent effect on apnea duration. Focal injection of WAY100635 in the cNTS also had no consistent effect on apnea duration, but injection of serotonin in this area shortened it. We conclude that serotonin within the NTS shortens the duration of LCR apnea, but this effect cannot be attributed solely to activation of 5HT‐1A receptors. Support: NIH grants HL36379 & HL42707

Distribution of electrical activation to the external intercostal muscles during high frequency spinal cord stimulation in dogs

In contrast to previous methods of electrical stimulation of the inspiratory muscles, high frequency spinal cord stimulation (HF-SCS) results in more physiological activation of these muscles. The spatial distribution of activation to the external intercostal muscles by this method is unknown. In anaesthetized dogs, multiunit and single motor unit (SMU) EMG activity was monitored in the dorsal portion of the 3rd, 5th and 7th interspaces and ventral portion of the 3rd interspace during spontaneous breathing and HF-SCS following C2 spinal section. Stimulus amplitude during HF-SCS was adjusted such that inspired volumes matched spontaneous breathing (Protocol 1). During HF-SCS, mean peak SMU firing frequency was highest in the 3rd interspace (dorsal) (18.8 ± 0.3 Hz) and significantly lower in the 3rd interspace (ventral) (12.2 ± 0.2 Hz) and 5th interspace (dorsal) (15.3 ± 0.3 Hz) (P <0.05 for each comparison). Similar rostrocaudal and dorsoventral gradients of activity were observed during spontaneous breathing prior to C2 section. No significant activity was observed in the 7th interspace during either spontaneous breathing or HF-SCS. Since peak discharge frequencies of the SMUs were higher and rib cage movement greater during HF-SCS compared to spontaneous breathing, stimulus amplitude during HF-SCS was adjusted such that rib cage movement matched (Protocol 2). Under these conditions, mean peak SMU frequencies and rostrocaudal and dorsoventral gradients of activity during HF-SCS were not significantly different compared to spontaneous breathing. These results indicate that (a) the topographic pattern of electrical activation of the external intercostal muscles during HF-SCS is similar to that occurring during spontaneous breathing and (b) differential descending synaptic input from supraspinal centres is not a required component of the differential spatial distribution of external intercostal muscle activation. HF-SCS may provide a more physiological method of inspiratory muscle pacing.

P124 Neuroventilatory uncoupling during cycle and treadmill exercise in COPD

BackgroundIt is widely accepted that neuroventilatory uncoupling drives breathlessness in COPD. COPD patients are more likely to stop exercising because of breathlessness during treadmill exercise than whilst cycling.AimTo test the...

Respiratory muscle activity and dyspnea during exercise in chronic obstructive pulmonary disease

We aimed to determine by non-invasive EMG, whether during exercise: (1) COPD patients increase scalene and intercostal EMG activity, (2) increased EMG activity is associated with increased dyspnea, and (3) the ratio between EMG activity and volume displacement is increased in COPD compared to healthy subjects (HS). During a maximal incremental cycle test, scalene and intercostal EMG was derived transcutaneously in 17 COPD patients and 10 HS. Dyspnea was quantified using a Borg scale, ranging from zero to 10 (maximal dyspnea). For analyses the ratio between inspiratory muscle activity during exercise and activity during quiet breathing was used (logEMGAR). In COPD patients, scalene and intercostal activity increased at greater rate early in exercise compared to that of the HS. With a doubling of the logEMGAR, in COPD, dyspnea increased with 2.8/3.8 points, while in the HS, dyspnea increased less with 1.1/1.4 points. In COPD, there was a larger increase in EMG activity relatively to tidal volume increases.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

Inspiratory Mouth Pressures And Motor Evoked Potentials Following Non-fatiguing Inspiratory Loading

We have shown previously that maximal inspiratory pressure (MIP) increases by 10% following prior inspiratory loaded breathing at 40% MIP (ILB) and that this increase is accompanied by increases in surface EMG of the diaphragm and intercostals. PURPOSE To examine the effect of an acute bout of ILB on the facilitation of cortically evoked motor evoked potentials (MEPs) during voluntary activation of the inspiratory muscles. METHODS Surface EMG from the chest wall was used to record diaphragm and intercostal EMG activity during an inspiratory effort of 50% MIP (MIP50), as well as MEPs evoked in the contralateral diaphragm and intercostals by transcranial magnetic stimulation of the motor cortex. MEPs were recorded during relaxation, MIP50 and maximal MIP (MIP 100) in 11 volunteers who gave informed consent, following Ethics committee approval. Mouth pressure was measured from an occluded airway. After baseline measurements, subjects performed ILB (two × 30 inspiratory efforts at 40% of initial MIP). Measurements were taken immediately after the first and second sets and 15 min after completion of the ILB. Data presented as means ± SEM., and compared using paired t-tests. RESULTS Values are expressed as percentage of baseline measures. RMS, root mean square;*, P = <0.05 Maximal MIP increased to 111+5%* of baseline after the first set of ILB, 115±5%* after the second set, and 107±4% 15 min after cessation of the breathing task.TableCONCLUSION The increase in MIP and RMS EMG after ILB confirm an increased activation and synergistic co ordination of the diaphragm and intercostal muscles during inspiratory efforts. The increase in MEPs during relaxed and MIP50 suggest that ILB increases the level of excitation in the inspiratory motoneurone pool. The decrease in MEPs during a MIP100 is difficult to interpret, but may indicate that with increased excitation and faster firing rates, some motor units become refractory. The changes in EMG and MEPs are maintained 15min following cessation of ILB indicating these modulations are not transient.

Clinical Effects of Theophylline on Inspiratory Muscle Drive in Tetraplegia

Theophylline has been shown to restore diaphragmatic function in animals following cervical spinal cord hemisection, which induces hemidiaphragm paralysis. Although theophylline had been used clinically in the treatment of various pulmonary diseases, its effects on respiratory muscle function in cervical spinal cord injured tetraplegics has not been studied. In the present case study, we evaluated a patient injured in 1979 with a chronic asymmetric C5-7 tetraplegia (left C5-6, right C6-7) before and after receiving theophylline chronically by mouth for three weeks and again before and after receiving acute intravenous (IV) aminophylline after the effects of the chronic drug administration wore off. Neural activation to inspiratory muscles was assessed by right and left parasternal intercostal and diaphragm EMGs during quiet breathing and max imal inspiratory efforts. Global respiratory drive was assessed by P100, and inspiratory muscle force was assessed by maximal inspiratory pressures and vital capacity. Both long-term orally administered and acute IV theophylline increased neural activation to the diaphragm, especially on the more affected left side. Theophylline treatment was also associated with an increase in global central respiratory drive and inspiratory muscle force, without changing expiratory airflows. Left diaphragm EMG activity was markedly increased following the administration of theophylline. Of interest, upper parasternal intercostal EMG activity was also recruited on the left in spite of being below the level of cervical injury. We speculate that the administration of theophylline in selected patients with an asymmetric cervical spinal cord injury may activate la tent bulbospinal respiratory pathways and improve inspiratory muscle function, re ducing the likelihood of associated respiratory failure.

Determinants of rib motion in flail chest.

We have previously developed a canine model of isolated flail chest to assess the effects of this condition on the mechanics of breathing, and these studies have led to the conclusion that the respiratory displacement of the fractured ribs is primarily determined by the fall in pleural pressure (Delta Ppl) and the action of the parasternal intercostal muscles. The present studies were designed to test the validity of this conclusion. A flail was induced in six supine anesthetized animals by fracturing both dorsally and ventrally the second to fifth ribs on the right side of the chest, after which the phrenic nerve roots were bilaterally sectioned in the neck. Sectioning the phrenic nerves caused a 34% decrease in Delta Ppl, associated with a 39% increase in parasternal intercostal inspiratory EMG activity (p < 0.05), and resulted in a marked reduction in the inspiratory inward displacement of the ribs. In three animals, the inward rib displacement was even reversed into a small outward displacement. When the airway was then occluded at end-expiration to increase Delta Ppl during the subsequent inspiration, all animals again showed a clear-cut inward rib displacement. These observations therefore confirm that in dogs with flail chest, the inspiratory displacement of the fractured ribs is set by the balance between the force related to pleural pressure and that generated by the parasternal intercostals. These observations also point to the critical importance of the pattern of inspiratory muscle activation in determining the magnitude of rib cage paradox in such patients.

Actions of the inspiratory intercostal muscles in flail chest.

We have previously shown in dogs that the ribs in flail chest move paradoxically inward during inspiration but continue to move cranially. We have also shown that flail elicits, probably via an increased activation of the muscle spindles, a threefold to fourfold increase in external intercostal inspiratory EMG activity without inducing any changes in parasternal intercostal activity. Therefore, the present studies were undertaken to test the hypothesis that the persistent cranial motion of the fractured ribs resulted primarily from the action of the external intercostals. A flail was induced in seven supine anesthetized animals by fracturing both dorsally and ventrally ribs 3 to 6 on the right side of the chest, after which the external intercostal muscles in interspaces 1 to 7 were severed. Severing the external intercostals caused a small increase in the inspiratory inward displacement of the fractured ribs, from 2.76 +/- 0.31 to 3.25 +/- 0.38 mm (p < 0.05), but it did not affect the parasternal intercostal EMG activity or the cranial rib displacement (before, 3.61 +/- 1.03 mm; after, 3.22 +/- 1.43 mm; NS). However, when the parasternal intercostals in interspaces 1 to 7 were also denervated, the inspiratory inward displacement of the ribs increased markedly to 5.95 +/- 0.48 mm (p < 0.01), and their inspiratory cranial displacement was reversed into a 1.05 +/- 0.58 mm inspiratory caudal displacement (p < 0.01). We conclude, therefore, that in dogs with flail chest the respiratory displacements of the ribs are still primarily determined, besides pleural pressure, by the action of the parasternal intercostals. These observations also suggest that in anesthetized dogs, spindle-induced excitation of the external intercostals has little impact on the mechanical behavior of the ribs.

Evaluation of role of upper cervical inspiratory neurons in respiration, emesis and cough

Upper cervical (C 1−3) inspiratory (UCI) propriospinal neurons project to spinal segments containing respiratory motoneurons, but their functional significance is unknown. Bilateral kainic acid injections into this cell column in 12 decerebrate cats (11 paralyzed and artificially ventilated) had no major effect on phrenic, intercostal, and abdominal nerve discharge or EMG activity during (fictive) respiration, vomiting and coughing. Thus, UCI neurons are unessential for activation of major respiratory muscles during these behaviors.

Evocation of postural atonia and respiratory depression by pontine carbachol in the decerebrate rat

To study mechanism underlying the postural muscle atonia and respiratory depression associated with rapid eye movement (REM) sleep, the cholinergic agonist, carbachol, was microinjected into the pontine reticular formation in decerebrate, spontaneously breathing rats. Carbachol injection led to a simultaneous depression of neck and tonic intercostal EMG activity (lasting 14.5 min±7.6 (S.D.)) and a reduction of the respiratory rate. Phasic inspiratory intercostal activity was not consistently depressed. After a spontanelously recovery from the atonia and respiratory depression, subsequent carbachol injections at the same site produced similar responses. Thus, the decerebrate rat may provide a useful model for studies of the inhibitory neural mechanisms activated by the increased acetylcholine levels in the pons that occur in REM sleep. Pontine carbachol effects in rats differ from those described in cats in a manner analogous to differences in the patterns of natural REM sleep in these two species.

Effects of non-REM sleep upon respiratory drive and the respiratory pump in humans

We observed that ventilation fell and end-tidal CO 2 rose in change from wakefulness to non-REM (NREM) sleep in 4 normal human subjects studied on two nights each. We hypothesized that the observed ventilatory depression was due to effects of sleep both upon the central respiratory neural output and upon the mechanical respiratory pump. Both the central controller response to CO 2, as measured by diaphragmatic and intercostal EMG activity, and the ability of the respiratory pump in effecting ventilation in response to diaphragmatic or intercostal EMG activitym abd the ability of the respiratory pump in effecting ventilation in response to diaphragmatic or intercostal activation, as measured by the relationhip between the EMG activities and minute ventilation, are reduced in NREM sleep. We described a general method of apportioning the separate effects of sleep, or other factors, upon the central respiratory controller, the respiratory mechanical pump, and the metabolic rate, in determining the total observed increase in end-tidal CO 2.

Respiratory EMG findings in relation to periodic breathing in infants

Intercostal and diaphragm EMG activity was analysed in periodically breathing infants. The aim was to investigate relationships between changes in tonic activity in the respiratory muscles and switches in spontaneous breathing pattern from periodic to continuous and vice versa. A heterogeneous group of 13 normal and neurologically suspect infants was studied. They had all previously undergone polygraphic investigation and were selected because their polygraphic records showed at least three minutes uninterrupted periodic breathing (PB). PB appeared to represent an oscillation with a length of about 16 seconds superimposed on the basic state related irregular and regular breathing patterns. The development of a normal level of tonic activity in the respiratory muscles at the transition from state 2 to state 1 coincided with the switching from periodic to continuous breathing. Continuation of PB throughout a state 1 epoch in the presence of tonic respiratory muscle activity was exceptional. Sighs alone or sighs together with brief movements during state 1 were followed on occasion by a drop in tonic activity and a switch from continuous to periodic breathing. If the tonic activity rose again, PB either stopped or became less pronounced. TcPO 2 level measured in four infants rose when tonic activity rose and was lower during PB than during continuous breathing. The observations made in this study suggest that mechanical or chemical changes caused by changes in tonic activity level may affect the stability of respiratory control in infancy.

Effect of thoracoabdominal configuration on the diaphragmatic contribution to rib cage motion.

Owing to the diaphragm-rib cage interaction the diaphragm can reduce the load on the intercostal muscles. The extent of this load reduction was evaluated by analyzing the EMG activity of intercostal muscles as an index of the pressure generated by the intercostal muscles. Three trained subjects shifted their breathing configuration while the rib cage volume and flow were kept constant. Analysis of data thus obtained indicated that the diaphragmatic contribution to the rib cage motion improved with a thoracic shift of breathing. The significance of this effect was further evaluated by performing respiratory maneuvers at constant tidal volume and flow at normal and elevated functional residual capacity. At both lung volumes, a substantial saving of diaphragmatic activity attained by the thoracic shift of breathing was associated with a moderate increase or even a decrease in the intercostal EMG activity, suggesting an overall mechanical advantage of inspiratory muscles during thoracic breathing.

Expiratory effects of brief carotid sinus nerve and carotid body stimulations

The expiratory response, measured directly as ventilatory volume and as internal intercostal or abdominal muscle EMG activity, to brief intermittent electrical stimulation of the carotid sinus nerve or chemical stimulation of the carotid body was determined in anesthetized cats. Stimuli given during expiration had a specific expiratory effect, manifested by increased expiratory duration, increased activity of expiratory muscles and increased depth of expiration. The later in expiration the stimulus was exhibited. the greater all effects became. Vagal section had no effect on the response and the duration of response persisted after spinal cord section at C 7-T 1 It is concluded that expiratory stimulations have effects on expiration similar to those on inspiration from stimulations given during inspiration. It is concluded that the mechanism operates at a brain stem level. However, because the latency of the response is much longer than the inspiratory response to the same stimuli, the pathway must be different.