RESUMO
Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.
Assuntos
Inalação , Reflexo , Músculos Respiratórios , Sistema Nervoso Simpático , Humanos , Masculino , Feminino , Sistema Nervoso Simpático/fisiologia , Adulto , Músculos Respiratórios/inervação , Músculos Respiratórios/fisiologia , Adulto Jovem , Fatores Sexuais , Pressão Arterial , Pressão Sanguínea , Trabalho RespiratórioRESUMO
OBJECTIVE: This study aimed to investigate the completion rates of a home-based randomized trial, which examined home-based high-intensity respiratory muscle training after stroke compared with sham intervention. MATERIALS AND METHODS: Completion was examined in terms of recruitment (enrolment and retention), intervention (adherence and delivery of home-visits) and measurement (collection of outcomes). RESULTS: Enrolment was 32% and retention was 97% at post-intervention and 84% at follow-up. Adherence to the intervention was high at 87%. Furthermore, 83% of planned home-visits were conducted and 100% of outcomes were collected from those attending measurement sessions. CONCLUSION: This home-based randomized trial demonstrated high rates of enrolment, retention, adherence, delivery of home-visits, and collection of outcomes. Home-based interventions may help to improve completion rates of randomized trials.
Assuntos
Serviços Hospitalares de Assistência Domiciliar , Respiração , Músculos Respiratórios/inervação , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Telerreabilitação , Exercícios Respiratórios , Visita Domiciliar , Humanos , Cooperação do Paciente , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Expiratory muscle weakness leads to difficult ventilator weaning. Maintaining their activity with functional electrical stimulation (FES) may improve outcome. We studied feasibility of breath-synchronized expiratory population muscle FES in a mixed ICU population ("Holland study") and pooled data with our previous work ("Australian study") to estimate potential clinical effects in a larger group. METHODS: Holland: Patients with a contractile response to FES received active or sham expiratory muscle FES (30 min, twice daily, 5 days/week until weaned). Main endpoints were feasibility (e.g., patient recruitment, treatment compliance, stimulation intensity) and safety. Pooled: Data on respiratory muscle thickness and ventilation duration from the Holland and Australian studies were combined (N = 40) in order to estimate potential effect size. Plasma cytokines (day 0, 3) were analyzed to study the effects of FES on systemic inflammation. RESULTS: Holland: A total of 272 sessions were performed (active/sham: 169/103) in 20 patients (N = active/sham: 10/10) with a total treatment compliance rate of 91.1%. No FES-related serious adverse events were reported. Pooled: On day 3, there was a between-group difference (N = active/sham: 7/12) in total abdominal expiratory muscle thickness favoring the active group [treatment difference (95% confidence interval); 2.25 (0.34, 4.16) mm, P = 0.02] but not on day 5. Plasma cytokine levels indicated that early FES did not induce systemic inflammation. Using a survival analysis approach for the total study population, median ventilation duration and ICU length of stay were 10 versus 52 (P = 0.07), and 12 versus 54 (P = 0.03) days for the active versus sham group. Median ventilation duration of patients that were successfully extubated was 8.5 [5.6-12.2] versus 10.5 [5.3-25.6] days (P = 0.60) for the active (N = 16) versus sham (N = 10) group, and median ICU length of stay was 10.5 [8.0-14.5] versus 14.0 [9.0-19.5] days (P = 0.36) for those active (N = 16) versus sham (N = 8) patients that were extubated and discharged alive from the ICU. During ICU stay, 3/20 patients died in the active group versus 8/20 in the sham group (P = 0.16). CONCLUSION: Expiratory muscle FES is feasible in selected ICU patients and might be a promising technique within a respiratory muscle-protective ventilation strategy. The next step is to study the effects on weaning and ventilator liberation outcome. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03453944. Registered 05 March 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03453944 .
Assuntos
Estimulação Elétrica/métodos , Músculos Respiratórios/inervação , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estimulação Elétrica/instrumentação , Estudos de Viabilidade , Feminino , Mortalidade Hospitalar/tendências , Humanos , Masculino , Medicare/estatística & dados numéricos , Medicare/tendências , Modelos de Riscos Proporcionais , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Músculos Respiratórios/fisiopatologia , Estudos Retrospectivos , Estados UnidosRESUMO
PURPOSE: Evidence supporting the utilization of surface EMG (sEMG) of extra-diaphragmatic muscles for monitoring of mechanical ventilation (MV) assistance is unclear. The purpose of this review was to assess the quality of literature available on using extra-diaphragmatic sEMG as an assessment technique of respiratory responses during MV. METHODS: Studies using sEMG of extra-diaphragmatic respiratory muscles during MV were selected by two independent researchers after performing a database search of PubMed, CINAHL, GOOGLE SCHOLAR. Exclusion criteria were studies of patients with neuromuscular disorders, receiving neuromuscular blocking agents, receiving non-invasive MV, using needle EMG, and studies written in languages other than English. Quality of identified studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). This study is registered with PROSPERO, number (CRD42018081341). RESULTS: 596 references were identified. Of the identified studies, 7 studies were included in the review. Findings demonstrate that sEMG of extra-diaphragmatic muscle activity is a valid and applicable tool to evaluate mechanical loading/unloading of respiratory muscles and respiratory drive or sensation. However, the quality of literature supporting sEMG as monitoring tool of respiratory responses were characterized by a high and unclear risk of bias. CONCLUSIONS: Although it appears to be a valid and applicable tool, there is a scarcity of literature that directly demonstrates the diagnostic accuracy of sEMG of extra-diaphragmatic muscles in monitoring respiratory mechanics and respiratory drive or sensation during MV assistance across wide populations and conditions.
Assuntos
Diafragma/fisiologia , Eletromiografia/métodos , Respiração Artificial/efeitos adversos , Músculos Respiratórios/fisiologia , Adolescente , Adulto , Viés , Bases de Dados Factuais , Diafragma/inervação , Estudos de Avaliação como Assunto , Humanos , Monitorização Fisiológica/instrumentação , Músculos Respiratórios/inervação , Adulto JovemRESUMO
Breathing requires precise control of respiratory muscles to ensure adequate ventilation. Neurons within discrete regions of the brainstem produce oscillatory activity to control the frequency of breathing. Less is understood about how spinal and pontomedullary networks modulate the activity of respiratory motor neurons to produce different patterns of activity during different behaviors (i.e., during exercise, coughing, swallowing, vocalizing, or at rest) or following disease or injury. Here, we use a chemogenetic approach to inhibit the activity of glutamatergic V2a neurons in the brainstem and spinal cord of neonatal and adult mice to assess their potential roles in respiratory rhythm generation and patterning respiratory muscle activity. Using whole-body plethysmography (WBP), we show that V2a neuron function is required in neonatal mice to maintain the frequency and regularity of respiratory rhythm. However, silencing V2a neurons in adult mice increases respiratory frequency and ventilation, without affecting regularity. Thus, the excitatory drive provided by V2a neurons is less critical for respiratory rhythm generation in adult compared to neonatal mice. In addition, we used simultaneous EMG recordings of the diaphragm and extradiaphragmatic respiratory muscles in conscious adult mice to examine the role of V2a neurons in patterning respiratory muscle activity. We find that silencing V2a neurons activates extradiaphragmatic respiratory muscles at rest, when they are normally inactive, with little impact on diaphragm activity. Thus, our results indicate that V2a neurons participate in a circuit that serves to constrain the activity of extradiaphragmatic respiratory muscles so that they are active only when needed.
Assuntos
Bulbo/fisiologia , Neurônios/fisiologia , Respiração , Músculos Respiratórios/fisiologia , Medula Espinal/fisiologia , Animais , Masculino , Camundongos Transgênicos , Músculos Respiratórios/inervaçãoRESUMO
This review is a comprehensive description of all muscles that assist lung inflation or deflation in any way. The developmental origin, anatomical orientation, mechanical action, innervation, and pattern of activation are described for each respiratory muscle fulfilling this broad definition. In addition, the circumstances in which each muscle is called upon to assist ventilation are discussed. The number of "respiratory" muscles is large, and the coordination of respiratory muscles with "nonrespiratory" muscles and in nonrespiratory activities is complex-commensurate with the diversity of activities that humans pursue, including sleep (8.27). The capacity for speech and adoption of the bipedal posture in human evolution has resulted in patterns of respiratory muscle activation that differ significantly from most other animals. A disproportionate number of respiratory muscles affect the nose, mouth, pharynx, and larynx, reflecting the vital importance of coordinated muscle activity to control upper airway patency during both wakefulness and sleep. The upright posture has freed the hands from locomotor functions, but the evolutionary history and ontogeny of forelimb muscles pervades the patterns of activation and the forces generated by these muscles during breathing. The distinction between respiratory and nonrespiratory muscles is artificial, as many "nonrespiratory" muscles can augment breathing under conditions of high ventilator demand. Understanding the ontogeny, innervation, activation patterns, and functions of respiratory muscles is clinically useful, particularly in sleep medicine. Detailed explorations of how the nervous system controls the multiple muscles required for successful completion of respiratory behaviors will continue to be a fruitful area of investigation. © 2019 American Physiological Society. Compr Physiol 9:1025-1080, 2019.
Assuntos
Mecânica Respiratória/fisiologia , Músculos Respiratórios/fisiologia , Animais , Desenvolvimento Fetal/fisiologia , Humanos , Mesoderma/anatomia & histologia , Recrutamento Neurofisiológico/fisiologia , Músculos Respiratórios/anatomia & histologia , Músculos Respiratórios/embriologia , Músculos Respiratórios/inervação , Sistema Respiratório/anatomia & histologia , Sono/fisiologia , Vigília/fisiologiaRESUMO
KEY POINTS: Central chemoreceptor stimulation, by hypercapnia (acidosis), and peripheral, by hypoxia plus hypercapnia, evoke reflex increases in ventilation and sympathetic outflow. The assumption that central or peripheral chemoreceptor-mediated sympathetic activation elicited when PCO2 increases parallels concurrent ventilatory responses is unproven. Applying a modified rebreathing protocol that equilibrates central and peripheral chemoreceptor PCO2 whilst clamping O2 tension at either hypoxic or hyperoxic concentrations, the independent ventilatory and muscle sympathetic stimulus-response properties of the central and peripheral chemoreflexes were quantified and compared in young men. The novel findings were that ventilatory and sympathetic responses to central and peripheral chemoreflex stimulation are initiated at similar PCO2 recruitment thresholds but individual specific sympathetic responsiveness cannot be predicted from the ventilatory sensitivities of either chemoreceptor reflex. Such findings in young men, if replicated in heart failure or hypertension, should temper present enthusiasm for trials targeting the peripheral chemoreflex based solely on ventilatory responsiveness to non-specific chemoreceptor stimulation. ABSTRACT: In humans, stimulation of peripheral or central chemoreceptor reflexes is assumed to evoke equivalent ventilatory and sympathetic responses. We evaluated whether central or peripheral chemoreceptor-mediated sympathetic activation elicited by increases in CO2 tension ( PCO2 ) parallels concurrent ventilatory responses. Twelve healthy young men performed a modified rebreathing protocol designed to equilibrate central and peripheral chemoreceptor PCO2 tensions with end-tidal PCO2 ( PETCO2 ) at two isoxic end-tidal PO2 ( PETO2 ) such that central responses can be segregated, by hyperoxia, from the net response (hypoxia minus hyperoxia). Ventilation and muscle sympathetic nerve activity (MSNA) were recorded continuously during rebreathing at isoxic PETO2 of 150 and 50 mmHg. During rebreathing, the PETCO2 values at which ventilation (L min-1 ) and total MSNA (units) began to rise were identified ( PETCO2 recruitment thresholds) and their slopes above the recruitment threshold were determined (sensitivity). The central chemoreflex recruitment threshold for ventilation (46 ± 3 mmHg) and MSNA (45 ± 4 mmHg) did not differ (P = 0.55) and slopes were 2.3 ± 0.9 L min-1 mmHg-1 and 2.1 ± 1.5 units mmHg-1 , respectively. The peripheral chemoreflex recruitment thresholds, at 41 ± 3 mmHg for both ventilation and MSNA were lower (P < 0.05) compared to the central chemoreflex recruitment thresholds. Peripheral chemoreflex sensitivity was 1.7 ± 0.1 L min-1 mmHg-1 for ventilation and 2.9 ± 2.6 units mmHg-1 for MSNA. There was no relationship between the ventilatory and MSNA sensitivity for either the central (r2 = 0.01, P = 0.76) or peripheral (r2 = 0.01, P = 0.73) chemoreflex. In healthy young men, ventilatory and sympathetic responses to central and peripheral chemoreceptor reflex stimulation are initiated at similar PETCO2 recruitment thresholds but individual ventilatory responsiveness does not predict sympathetic sensitivities of either chemoreflex.
Assuntos
Sistema Nervoso Central/fisiologia , Células Quimiorreceptoras/fisiologia , Ventilação Pulmonar/fisiologia , Músculos Respiratórios/inervação , Sistema Nervoso Simpático/fisiologia , Adulto , Dióxido de Carbono/metabolismo , Sistema Nervoso Central/metabolismo , Células Quimiorreceptoras/metabolismo , Humanos , Hiperóxia/metabolismo , Hiperóxia/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Reflexo/fisiologia , Respiração , Mecânica Respiratória/fisiologia , Músculos Respiratórios/fisiologia , Sistema Nervoso Simpático/metabolismo , Ventilação/métodosRESUMO
Amphibian respiratory development involves a dramatic metamorphic transition from gill to lung breathing and coordination of distinct motor outputs. To determine whether the emergence of adult respiratory motor patterns was associated with similarly dramatic changes in motoneuron (MN) properties, we characterized the intrinsic electrical properties of American bullfrog trigeminal MNs innervating respiratory muscles comprising the buccal pump. In premetamorphic tadpoles (TK stages IX-XVIII) and adult frogs, morphometric analyses and whole cell recordings were performed in trigeminal MNs identified by fluorescent retrograde labeling. Based on the amplitude of the depolarizing sag induced by hyperpolarizing voltage steps, two MN subtypes (I and II) were identified in tadpoles and adults. Compared with type II MNs, type I MNs had larger sag amplitudes (suggesting a larger hyperpolarization-activated inward current), greater input resistance, lower rheobase, hyperpolarized action potential threshold, steeper frequency-current relationships, and fast firing rates and received fewer excitatory postsynaptic currents. Postmetamorphosis, type I MNs exhibited similar sag, enhanced postinhibitory rebound, and increased action potential amplitude with a smaller-magnitude fast afterhyperpolarization. Compared with tadpoles, type II MNs from frogs received higher-frequency, larger-amplitude excitatory postsynaptic currents. Input resistance decreased and rheobase increased postmetamorphosis in all MNs, concurrent with increased soma area and hyperpolarized action potential threshold. We suggest that type I MNs are likely recruited in response to smaller, buccal-related synaptic inputs as well as larger lung-related inputs, whereas type II MNs are likely recruited in response to stronger synaptic inputs associated with larger buccal breaths, lung breaths, or nonrespiratory behaviors involving powerful muscle contractions.
Assuntos
Brânquias/crescimento & desenvolvimento , Brânquias/fisiologia , Pulmão/crescimento & desenvolvimento , Pulmão/fisiologia , Metamorfose Biológica/fisiologia , Neurônios Motores/fisiologia , Rana catesbeiana/fisiologia , Músculos Respiratórios/inervação , Músculos Respiratórios/fisiologia , Potenciais de Ação/fisiologia , Animais , Bochecha/inervação , Bochecha/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Transmissão Sináptica/fisiologia , Nervo Trigêmeo/fisiologiaRESUMO
The inspiratory motor activities are greater in the intercostal muscles positioned at more rostral thoracic segments. This rostro-caudal gradient of the thoracic inspiratory motor activity is thought to be generated by the spinal interneurons. To clarify the involvement of the inhibitory thoracic interneurons in this rostro-caudal gradient, we examined the effects of 10⯵M strychnine, an antagonist of glycine and GABAA receptors, applied to the neonatal rat thoracic spinal cord. The respiratory-related interneuron activities were optically recorded from thoracic segments in the isolated neonatal rat brainstem-spinal cord preparations stained with voltage-sensitive dye, and the electrical inspiratory motor activities were obtained from the third and eleventh thoracic ventral roots (T3VR, T11VR). Although strychnine caused seizure-like activities in all of the ventral roots recorded, the inspiratory motor activities continued. The inspiratory optical signals in the rostral thoracic segments (T2-T5) were significantly larger than those in the caudal thoracic segments (T9-T11) regardless of the existence of strychnine. Similarly, the percent ratio of the amplitude of the inspiratory electrical activity in the T3VR under control and strychnine was significantly larger than that in the T11VR regardless of the existence of strychnine. Strychnine significantly increased the inspiratory activity in both the T3VR and T11VR. These results suggest that the glycinergic and GABAergic inhibitory interneurons are not essential to generate the rostro-caudal gradient in the neonatal rat thoracic inspiratory motor outputs, but these interneurons are likely to play a role in the inhibitory control of inspiratory motor output.
Assuntos
Inalação/fisiologia , Interneurônios/fisiologia , Movimento/fisiologia , Inibição Neural/fisiologia , Músculos Respiratórios/fisiologia , Raízes Nervosas Espinhais/fisiologia , Animais , Animais Recém-Nascidos , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Glicina/metabolismo , Inalação/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Movimento/efeitos dos fármacos , Inibição Neural/efeitos dos fármacos , Neurotransmissores/farmacologia , Ratos Wistar , Receptores de GABA-A/metabolismo , Receptores de Glicina/antagonistas & inibidores , Receptores de Glicina/metabolismo , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/inervação , Convulsões/fisiopatologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Estricnina/farmacologia , Vértebras Torácicas , Técnicas de Cultura de Tecidos , Imagens com Corantes Sensíveis à Voltagem , Ácido gama-Aminobutírico/metabolismoRESUMO
KEY POINTS: A cortical contribution to breathing, as indicated by a Bereitschaftspotential (BP) in averaged electroencephalographic signals, occurs in healthy individuals when external inspiratory loads are applied. Chronic obstructive pulmonary disease (COPD) is a condition where changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. These changes also occur in normal ageing, although to a lesser extent. In the present study, we determined whether BPs are present during quiet breathing and breathing with an external inspiratory load in COPD compared to age-matched and young healthy controls. We demonstrated that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea (i.e. the sensation of breathlessness). We propose that cortical mechanisms may be engaged to defend ventilation in ageing with dyspnoea as a consequence. ABSTRACT: A cortical contribution to breathing is determined by the presence of a Bereitschaftspotential, a low amplitude negativity in the averaged electroencephalographic (EEG) signal, which begins â¼1 s before inspiration. It occurs in healthy individuals when external inspiratory loads to breathing are applied. In chronic obstructive pulmonary disease (COPD), changes in the lung, chest wall and respiratory muscles produce an internal inspiratory load. We hypothesized that there would be a cortical contribution to quiet breathing in COPD and that a cortical contribution to breathing with an inspiratory load would be linked to dyspnoea, a major symptom of COPD. EEG activity was analysed in 14 participants with COPD (aged 57-84 years), 16 healthy age-matched (57-87 years) and 15 young (18-26 years) controls during quiet breathing and inspiratory loading. The presence of Bereitschaftspotentials, from ensemble averages of EEG epochs at Cz and FCz, were assessed by blinded assessors. Dyspnoea was rated using the Borg scale. The incidence of a cortical contribution to quiet breathing was significantly greater in participants with COPD (6/14) compared to the young (0/15) (P = 0.004) but not the age-matched controls (6/16) (P = 0.765). A cortical contribution to inspiratory loading was associated with higher Borg ratings (P = 0.007), with no effect of group (P = 0.242). The data show that increased age, rather than COPD, is associated with a cortical contribution to quiet breathing. A cortical contribution to inspiratory loading is associated with more severe dyspnoea. We propose that cortical mechanisms may be engaged to defend ventilation with dyspnoea as a consequence.
Assuntos
Potenciais Evocados , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Respiração , Músculos Respiratórios/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Dispneia , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Respiratórios/inervação , Adulto JovemRESUMO
Inhibitory afferent inputs to pontine A5 noradrenergic neurons (A5 NN) are not known, except partial baroreceptor input. In spontaneously breathing pentobarbital-anesthetized rats, we registered 35 A5 NN that were activated by hypoxia (100% N2, 10 sec) by more than 5 times in comparison with the background. Cooling of retrotrapezoid nucleus (15°C, 6 sec) completely blocked the motor inspiratory output and A5 NN discharge frequency increased (23/23) by more than 7 times in comparison with the background values. The beginning of A5 NN activation coincided with cessation of inspiratory activity. Short-term passive stretching of the shin muscles (1 sec, 100 g) caused BP drop and complete inhibition of A5 NN (12/12) activated by hypoxia. Inhibitory afferent inputs from proprioceptors and central inspiratory neurons that can limit A5 NN activity were demonstrated.
Assuntos
Neurônios Adrenérgicos/fisiologia , Neurônios Aferentes/fisiologia , Ponte/citologia , Propriocepção/fisiologia , Respiração , Sistema Nervoso Simpático/fisiologia , Animais , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Masculino , Pressorreceptores/fisiologia , Ratos , Ratos Wistar , Músculos Respiratórios/inervação , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologiaRESUMO
Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator assistance. Thus restoring diaphragm activity and regaining voluntary control of breathing are the primary clinical goals for patients with respiratory dysfunction following cervical SCI. Epidural stimulation (EDS) is a promising strategy that has been explored extensively for nonrespiratory functions and to a limited extent within the respiratory system. The goal of the present study is to assess the potential for EDS at the location of the phrenic nucleus (C3-C5) innervating the diaphragm: the main inspiratory muscle following complete C1 cervical transection. To avoid the suppressive effect of anesthesia, all experiments were performed in decerebrate, C1 cervical transection, unanesthetized, nonparalyzed ( n = 13) and paralyzed ( n = 7) animals. Our results show that C4 segment was the most responsive to EDS and required the lowest threshold of current intensity, affecting tracheal pressure and phrenic nerve responses. High-frequency (200-300 Hz) EDS applied over C4 segment (C4-EDS) was able to maintain breathing with normal end-tidal CO2 level and raise blood pressure. In addition, 100-300 Hz of C4-EDS showed time- and frequency-dependent changes (short-term facilitation) of evoked phrenic nerve responses that may serve as a target mechanism for pacing of phrenic motor circuits. The present work provides the first report of successful EDS at the level of phrenic nucleus in a complete SCI animal model and offers insight into the potential therapeutic application in patients with high cervical SCI. NEW & NOTEWORTHY The present work offers the first demonstration of successful life-supporting breathing paced by epidural stimulation (EDS) at the level of the phrenic nucleus, following a complete spinal cord injury in unanesthetized, decerebrate rats. Moreover, our experiments showed time- and frequency-dependent changes of evoked phrenic nerve activity during EDS that may serve as a target mechanism for pacing spinal phrenic motor networks.
Assuntos
Medula Cervical/lesões , Espaço Epidural , Nervo Frênico , Respiração , Traumatismos da Medula Espinal/fisiopatologia , Animais , Pressão Sanguínea , Dióxido de Carbono , Estado de Descerebração/fisiopatologia , Estimulação Elétrica , Frequência Cardíaca , Masculino , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Músculos Respiratórios/inervaçãoRESUMO
Mid-cervical spinal cord contusion disrupts both the pathways and motoneurons vital to the activity of inspiratory muscles. The present study was designed to determine if a rat contusion model could result in a measurable deficit to both ventilatory and respiratory motor function under "normal" breathing conditions at acute to chronic stages post trauma. Through whole body plethysmography and electromyography we assessed respiratory output from three days to twelve weeks after a cervical level 3 (C3) contusion. Contused animals showed significant deficits in both tidal and minute volumes which were sustained from acute to chronic time points. We also examined the degree to which the contusion injury impacted ventilatory pattern variability through assessment of Mutual Information and Sample Entropy. Mid-cervical contusion significantly and robustly decreased the variability of ventilatory patterns. The enduring deficit to the respiratory motor system caused by contusion was further confirmed through electromyography recordings in multiple respiratory muscles. When isolated via a lesion, these contused pathways were insufficient to maintain respiratory activity at all time points post injury. Collectively these data illustrate that, counter to the prevailing literature, a profound and lasting ventilatory and respiratory motor deficit may be modelled and measured through multiple physiological assessments at all time points after cervical contusion injury.
Assuntos
Vértebras Cervicais/lesões , Contusões/fisiopatologia , Respiração , Traumatismos da Medula Espinal/fisiopatologia , Animais , Eletromiografia , Entropia , Masculino , Pletismografia , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória , Músculos Respiratórios/inervação , Músculos Respiratórios/fisiopatologia , Volume de Ventilação PulmonarRESUMO
This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman's rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.
Assuntos
Potenciais de Ação , Resistência das Vias Respiratórias , Eletromiografia , Inalação , Junção Neuromuscular/fisiologia , Músculos Respiratórios/inervação , Adulto , Estudos Transversais , Voluntários Saudáveis , Humanos , Masculino , Respiração Artificial , Taxa Respiratória , Fatores de TempoAssuntos
Movimento Fetal/fisiologia , Músculo Esquelético/metabolismo , Junção Neuromuscular/metabolismo , Receptor Notch1/metabolismo , Músculos Respiratórios/metabolismo , Animais , Animais Recém-Nascidos , Humanos , Camundongos Transgênicos , Desenvolvimento Muscular/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/inervação , Junção Neuromuscular/crescimento & desenvolvimento , Receptor Notch1/genética , Respiração , Músculos Respiratórios/crescimento & desenvolvimento , Músculos Respiratórios/inervaçãoRESUMO
CONTEXT: Spinal cord stimulation (SCS) via disc electrodes surgically placed via laminotomy incisions has been shown to restore an effective cough in subjects with spinal cord injury (SCI). The purpose of this study was to evaluate a new method of expiratory muscle activation utilizing spinal cord wire leads, which can be implanted with minimally invasive techniques. METHODS: In a subject with SCI, parallel wire leads with two electrode contacts were inserted percutaneously through a needle, advanced to the T9, T11 spinal levels and connected to an implanted radiofrequency receiver. Stimulus parameters were set at values resulting in near maximum airway pressure generation (Paw) (40V, 50Hz, 0.2ms). Paw was measured at functional residual capacity (FRC) and total lung capacity (TLC) as an index of expiratory muscle strength. RESULTS: Paw during spontaneous efforts was 20 cmH2O (8.6% predicted). Bipolar (T9-T11) SCS resulted in Paw of 84 and 103 cmH2O, at FRC and TLC respectively. Monopolar (T9 only) SCS resulted in Paw of 61 and 86 cmH2O, at FRC and TLC respectively. This subject experienced much greater ease in raising secretions with use of SCS and no longer required other methods of secretion management. CONCLUSION: SCS via wire leads, which can be implanted using minimally invasive techniques, may provide a new useful method to restore an effective cough and possibly reduce the morbidity and mortality associated with respiratory tract infections in patients with SCI.
Assuntos
Tosse/fisiopatologia , Músculos Respiratórios/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Estimulação da Medula Espinal/métodos , Eletrodos Implantados , Humanos , Masculino , Pessoa de Meia-Idade , Músculos Respiratórios/inervação , Estimulação da Medula Espinal/instrumentaçãoRESUMO
Coordination of respiratory pump and valve muscle activity is essential for normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is the emergence of active exhalation, characterized by abdominal muscle pumping during the late one-third of expiration (late-E phase). Late-E abdominal activity during hypercapnia has been attributed to the activation of expiratory neurons located within the parafacial respiratory group (pFRG). However, the mechanisms that control emergence of active exhalation, and its silencing in restful breathing, are not completely understood. We hypothesized that inputs from the Kölliker-Fuse nucleus (KF) control the emergence of late-E activity during hypercapnia. Previously, we reported that reversible inhibition of the KF reduced postinspiratory (post-I) motor output to laryngeal adductor muscles and brought forward the onset of hypercapnia-induced late-E abdominal activity. Here we explored the contribution of the KF for late-E abdominal recruitment during hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate arterially perfused rat preparations. These data were combined with previous results and incorporated into a computational model of the respiratory central pattern generator. Disinhibition of the KF through local parenchymal microinjections of gabazine (GABAA receptor antagonist) prolonged vagal post-I activity and inhibited late-E abdominal output during hypercapnia. In silico, we reproduced this behavior and predicted a mechanism in which the KF provides excitatory drive to post-I inhibitory neurons, which in turn inhibit late-E neurons of the pFRG. Although the exact mechanism proposed by the model requires testing, our data confirm that the KF modulates the formation of late-E abdominal activity during hypercapnia. NEW & NOTEWORTHY The pons is essential for the formation of the three-phase respiratory pattern, controlling the inspiratory-expiratory phase transition. We provide functional evidence of a novel role for the Kölliker-Fuse nucleus (KF) controlling the emergence of abdominal expiratory bursts during active expiration. A computational model of the respiratory central pattern generator predicts a possible mechanism by which the KF interacts indirectly with the parafacial respiratory group and exerts an inhibitory effect on the expiratory conditional oscillator.
Assuntos
Hipercapnia/fisiopatologia , Núcleo de Kölliker-Fuse/fisiologia , Nervos Periféricos/fisiologia , Respiração , Animais , Geradores de Padrão Central/fisiologia , Potencial Evocado Motor , Núcleo de Kölliker-Fuse/fisiopatologia , Masculino , Modelos Neurológicos , Nervos Periféricos/fisiopatologia , Ratos , Ratos Wistar , Músculos Respiratórios/inervaçãoRESUMO
OBJECTIVE: To optimize maximal respiratory responses with surface stimulation over abdominal and upper thorax muscles and using a 12-Channel Neuroprosthetic Platform. METHODS: Following instrumentation, six anesthetized adult canines were hyperventilated sufficiently to produce respiratory apnea. Six abdominal tests optimized electrode arrangements and stimulation parameters using bipolar sets of 4.5â cm square electrodes. Tests in the upper thorax optimized electrode locations, and forelimb moment was limited to slight-to-moderate. During combined muscle stimulation tests, the upper thoracic was followed immediately by abdominal stimulation. Finally, a model of glottal closure for cough was conducted with the goal of increased peak expiratory flow. RESULTS: Optimized stimulation of abdominal muscles included three sets of bilateral surface electrodes located 4.5â cm dorsal to the lateral line and from the 8th intercostal space to caudal to the 13th rib, 80 or 100â mA current, and 50â Hz stimulation frequency. The maximal expired volume was 343 ± 23â ml (n=3). Optimized upper thorax stimulation included a single bilateral set of electrodes located over the 2nd interspace, 60 to 80â mA, and 50â Hz. The maximal inspired volume was 304 ± 54â ml (n=4). Sequential stimulation of the two muscles increased the volume to 600 ± 152â ml (n=2), and the glottal closure maneuver increased the flow. CONCLUSIONS: Studies in an adult canine model identified optimal surface stimulation methods for upper thorax and abdominal muscles to induce sufficient volumes for ventilation and cough. Further study with this neuroprosthetic platform is warranted.
Assuntos
Músculos Abdominais/inervação , Tosse/fisiopatologia , Respiração , Insuficiência Respiratória/fisiopatologia , Músculos Respiratórios/inervação , Traumatismos da Medula Espinal/complicações , Estimulação Elétrica Nervosa Transcutânea/métodos , Músculos Abdominais/fisiopatologia , Animais , Cães , Masculino , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Músculos Respiratórios/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea/efeitos adversosRESUMO
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG muscle activity during NREM sleep (F1,1,3=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG muscle activity, suggesting that A1/C1 neurons regulate upper airway patency in a state-independent manner.
Assuntos
Catecolaminas/metabolismo , Nervo Hipoglosso/fisiologia , Bulbo/fisiologia , Músculos Respiratórios/fisiologia , Fases do Sono/fisiologia , Vigília/fisiologia , Animais , Eletroencefalografia , Eletromiografia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios Motores/fisiologia , Músculos do Pescoço/inervação , Músculos do Pescoço/fisiologia , Vias Neurais/fisiologia , Receptores de Catecolaminas/genética , Receptores de Catecolaminas/metabolismo , Músculos Respiratórios/inervaçãoRESUMO
Twitch mouth pressure using magnetic stimulation of the phrenic nerves and an automated inspiratory trigger is a noninvasive, non-volitional assessment of diaphragmatic strength. Our aims were to validate this method in patients with suspected neuromuscular disease, to determine the best inspiratory-trigger pressure threshold, and to evaluate whether twitch mouth pressure decreased the overdiagnosis of muscle weakness frequently observed with noninvasive volitional tests. Maximal inspiratory pressure, sniff nasal pressure, and twitch mouth pressure were measured in 112 patients with restrictive disease and suspected neuromuscular disorder. Esophageal and transdiaphragmatic pressures were measured in 64 of these patients to confirm or infirm inspiratory muscle weakness. Magnetic stimulation was triggered by inspiratory pressures of -1 and -5 cmH2O. The -5 cmH2O trigger produced the best correlation between twitch mouth pressure and twitch esophageal pressure (R2 = 0.86; P <0.0001). The best association of noninvasive tests to predict inspiratory muscle weakness was sniff nasal pressure and twitch mouth pressure. Below-normal maximal inspiratory pressure and sniff nasal pressure values suggesting inspiratory muscle weakness were found in 63/112 patients. Only 52 of these 63 patients also had abnormal twitch mouth pressure. In conclusion twitch mouth pressure measurement is a simple, noninvasive, nonvolitional technique which may help to select patients with suspected neuromuscular disorder for invasive inspiratory-muscle investigation.