Asunto(s)

Traumatismos del Nacimiento , Enfermedades del Sistema Nervioso Periférico , Parálisis Respiratoria , Traumatismos del Nacimiento/complicaciones , Traumatismos del Nacimiento/diagnóstico por imagen , Diafragma/diagnóstico por imagen , Diafragma/lesiones , Diafragma/inervación , Humanos , Parálisis , Nervio Frénico/lesiones , Parálisis Respiratoria/diagnóstico por imagen , Parálisis Respiratoria/etiología

RESUMEN

BACKGROUND: Traumatic brachial plexus injuries are devastating lesions, and neurotization is an usually elected surgical therapy. The phrenic nerve has been harvested as a motor fibers donor in brachial plexus neurotization, showing great results in terms of motor reinnervation. Unfortunately, these interventions lack solid evidence regarding long-term safety and possible late respiratory function sequelae, raising crescent concerns after the COVID-19 pandemic onset and possibly resulting in reduced propensity to use this technique. The study of the distal anatomy of the phrenic nerves may lead to a better understanding of their branching patterns, and thus the proposition of surgical approaches that better preserve patient respiratory function. METHODS: Twenty-one phrenic nerves in 10 formalized cadavers were scrutinized. Prediaphragmatic branching patterns were inspected through analysis of the distance between the piercing site of the nerve at the diaphragm and the cardiac structures, number of divisions, and length from the point where the main trunk emits its branches to the diaphragm. RESULTS: The main trunk of the right phrenic nerve reaches the diaphragm near the inferior vena cava and branches into 3 major divisions. The left phrenic nerve reaches the diaphragm in variable locations near the heart, branching into 2-5 main trunks. Moreover, we noticed a specimen presenting 2 ipsilateral parallel phrenic nerves. CONCLUSIONS: The right phrenic nerve presented greater consistency concerning insertion site, terminal branching point distance to this muscle, and number of rami than the left phrenic nerve.

Asunto(s)

COVID-19 , Transferencia de Nervios , Diafragma/inervación , Humanos , Transferencia de Nervios/métodos , Pandemias , Nervio Frénico

RESUMEN

Active expiration represents an important mechanism to improve ventilation in conditions of augmented ventilatory demand, such as hypercapnia. While a rostral ventromedullary region, the parafacial respiratory group (pFRG), has been identified as a conditional expiratory oscillator, little is known about how central chemosensitive sites contribute to modulate active expiration under hypercapnia. In this study, we investigated the influence of the medullary raphe in the emergence of phasic expiratory abdominal activity during hypercapnia in unanesthetized adult male rats, in a state-dependent manner. To do so, reverse microdialysis of muscimol (GABAA receptor agonist, 1 mM) or 8-OH-DPAT (5-HT1A agonist, 1 mM) was applied in the MR during sleep and wakefulness periods, both in normocapnic (room air) and hypercapnic conditions (7% CO2). Electromyography (EMG) of diaphragm and abdominal muscles was performed to measure inspiratory and expiratory motor outputs. We found that active expiration did not occur in room air exposure during wakefulness or sleep. However, hypercapnia did recruit active expiration, and differential effects were observed with the drug dialyses in the medullary raphe. Muscimol increased the diaphragm inspiratory motor output and also increased the amplitude and frequency of abdominal expiratory rhythmic activity during hypercapnia in wakefulness periods. On the other hand, the microdialysis of 8-OH-DPAT attenuated hypercapnia-induced active expiration in a state-dependent manner. Our data suggest that the medullary raphe can either inhibit or potentiate respiratory motor activity during hypercapnia, and the balance of these inhibitory or excitatory outputs may determine the expression of active expiration.

Asunto(s)

Diafragma/fisiopatología , Espiración , Hipercapnia/fisiopatología , Núcleos del Rafe/fisiopatología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Músculos Abdominales/inervación , Músculos Abdominales/fisiopatología , Animales , Diafragma/inervación , Agonistas de Receptores de GABA-A/farmacología , Masculino , Muscimol/farmacología , Contracción Muscular , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Agonistas de Receptores de Serotonina/farmacología , Sueño , Vigilia

RESUMEN

To assess the impact of vagotomy on the IgA-response, male BALB/c mice underwent anterior vagotomy or a sham procedure were sacrificed on day 14 post-operation and the proximal and distal small-gut segments were dissected. In intestinal lavages IgA/IgM antibodies were analysed by ELISA; in Peyer's-patches and lamina-propria cell suspensions the intracellular IgA-associated interleukins (ILs) and pro-inflammatory cytokines in CD4+ T cells were analysed by cytofluorometry. Vagotomy reduced the IgA or increased the IgM antibody concentration in both segments and reduced or increased the lamina- propria CD4+ T cell pro-inflammatory cytokine responses in the distal or proximal segments, respectively. Data show the role of the vagus nerve on the IgA response.

Asunto(s)

Formación de Anticuerpos/fisiología , Diafragma/inervación , Inmunoglobulina A/sangre , Intestino Delgado/metabolismo , Ganglios Linfáticos Agregados/metabolismo , Vagotomía/tendencias , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Inmunoglobulina A/inmunología , Intestino Delgado/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ganglios Linfáticos Agregados/inmunología , Vagotomía/efectos adversos

RESUMEN

BACKGROUND: Paralysis of the diaphragm in newborn infants can lead to recurrent infections and life-threatening respiratory insufficiency. The clinical diagnosis of unilateral diaphragmatic paralysis has been reported in infants with laboratory evidence of congenital Zika virus infection and/or the congenital Zika syndrome (CZS) phenotype but no evaluation of phrenic nerve function has been described. All reported infants have had accompanying arthrogryposis. High infant mortality is reported. METHODS: The causal mechanism of congenital diaphragmatic paralysis was evaluated in three infants with arthrogryposis as a manifestation of CZS (two of the three infants had laboratory evidence of ZIKV infection shortly after birth; the remaining infant had negative serology for ZIKV when first tested at 7 months of age). Electromyography and phrenic nerve compound muscle action potential (CMAP) were performed in all infants with diaphragmatic paralysis demonstrated on imaging studies. RESULTS: All infants had evidence of moderate chronic involvement of peripheral motor neurons. Phrenic nerve CMAP was reduced on the side of the diaphragmatic paralysis in two infants and reduced bilaterally in the remaining infant who had primarily anterior involvement of the diaphragm. All three infants had multiple medical complications and one infant died at 18 months of age. CONCLUSION: Evaluation of three infants with CZS and diaphragmatic paralysis demonstrated phrenic nerve dysfunction. In these and other affected infants, arthrogryposis appears to be a constant co-occurring condition and health problems are significant; both conditions are likely due to involvement of the peripheral nervous system in some infants with CZS.

Asunto(s)

Parálisis Respiratoria/complicaciones , Parálisis Respiratoria/etiología , Parálisis Respiratoria/fisiopatología , Artrogriposis/fisiopatología , Artrogriposis/virología , Brasil , Diafragma/inervación , Diafragma/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Nervio Frénico/metabolismo , Nervio Frénico/virología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Virus Zika/patogenicidad , Infección por el Virus Zika/complicaciones

RESUMEN

Nanoparticle-conjugated venom-toxins of venomous animals and its therapeutic efficacy against emerging or neglecting diseases is a promising strategy. In this study, silver nanoparticles (AgNPs ∼50 nm, 0.081 mg mL-1) were studied against the neuromuscular blockade, myotoxic effects induced by Bothrops jararacussu venom (60 µg mL-1) and also against prokaryotic cells. The neurotoxicity was evaluated on ex vivo mouse phrenic nerve-diaphragm using traditional myographic technique, able to obtain functional contractile responses and to check the neurotransmission. The myotoxicity on mammalian cells was evaluated in muscles resulting from pharmacological assays using routine histological techniques and light microscopy. The toxicity to prokaryotic cells was evaluated on Salmonella typhimurium TA100 without metabolic activation. The in vitro preincubation model between AgNPs and venom was enough to abolish toxic effects of B. jararacussu venom, but mammalian cells were highly sensitive to AgNPs more than prokaryotic cells, by acting as dose-independently and dose-dependently parameters, respectively. These results allowed us to conclude that AgNPs showed promising activity as antivenom agent but for its safer use, the toxicity should be evaluated on experimental animals.

Asunto(s)

Antídotos/farmacología , Bothrops , Nanopartículas del Metal/química , Salmonella typhimurium/efectos de los fármacos , Plata/farmacología , Venenos de Serpiente/toxicidad , Animales , Antídotos/química , Antídotos/toxicidad , Diafragma/efectos de los fármacos , Diafragma/inervación , Relación Dosis-Respuesta a Droga , Técnicas In Vitro , Masculino , Ratones , Tono Muscular/efectos de los fármacos , Nervio Frénico/efectos de los fármacos , Plata/química , Plata/toxicidad , Venenos de Serpiente/química

RESUMEN

The neuromuscular effect of venoms is not a major clinical manifestation shared between rattlesnakes native to the Americas, which showed two different venom phenotypes. Taking into account this dichotomy, nerve muscle preparations from mice and chicks were used to investigate the ability of Crotalus atrox venom to induce in vitro neurotoxicity and myotoxicity. Unlike crotalic venoms of South America, low concentrations of C. atrox venom did not result in significant effects on mouse neuromuscular preparations. The venom was more active on avian nerve-muscle, showing reduction of twitch heights after 120 min of incubation with 10, 30 and 100 µg/mL of venom with diminished responses to agonists and KCl. Histological analysis highlighted that C. atrox was myotoxic in both species of experimental animals; as evidenced by degenerative events, including edematous cells, delta lesions, hypercontracted fibers and muscle necrosis, which can lead to neurotoxic action. These results provide key insights into the myotoxicity and low neurotoxicity of C. atrox in two animal models, corroborating with previous genomic and proteomic findings and would be useful for a deeper understanding of venom evolution in snakes belonging to the genus Crotalus.

Asunto(s)

Venenos de Crotálidos/farmacología , Crotalus/fisiología , Músculo Esquelético/efectos de los fármacos , Fibras Nerviosas/efectos de los fármacos , Bloqueantes Neuromusculares/farmacología , Unión Neuromuscular/efectos de los fármacos , Animales , Pollos , Crotalus/crecimiento & desarrollo , Diafragma/citología , Diafragma/efectos de los fármacos , Diafragma/inervación , Diafragma/fisiología , Resistencia a Medicamentos , Técnicas In Vitro , Masculino , Ratones , Contracción Muscular/efectos de los fármacos , Músculo Esquelético/citología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Fibras Nerviosas/fisiología , Unión Neuromuscular/fisiología , América del Norte , Especificidad de Órganos , Músculos Paraespinales/citología , Músculos Paraespinales/efectos de los fármacos , Músculos Paraespinales/inervación , Músculos Paraespinales/fisiología , Nervio Frénico/citología , Nervio Frénico/efectos de los fármacos , Nervio Frénico/fisiología , Especificidad de la Especie , Nervios Espinales/citología , Nervios Espinales/efectos de los fármacos , Nervios Espinales/fisiología

RESUMEN

OBJECTIVE: Our objective in this study was to extend diaphragmatic pacing therapy to include paraplegic patients with high cervical spinal cord injuries between C3 and C5. INTRODUCTION: Diaphragmatic pacing has been used in patients experiencing ventilator-dependent respiratory failure due to spinal cord injury as a means to reduce or eliminate the need for mechanical ventilation. However, this technique relies on intact phrenic nerve function. Recently, phrenic nerve reconstruction with intercostal nerve grafting has expanded the indications for diaphragmatic pacing. Our study aimed to evaluate early outcomes and efficacy of intercostal nerve transfer in diaphragmatic pacing. METHODS: Four ventilator-dependent patients with high cervical spinal cord injuries were selected for this study. Each patient demonstrated absence of phrenic nerve function via external neck stimulation and laparoscopic diaphragm mapping. Each patient underwent intercostal to phrenic nerve grafting with implantation of a phrenic nerve pacer. The patients were followed, and ventilator dependence was reassessed at 1 year postoperatively. RESULTS: Our primary outcome was measured by the amount of time our patients tolerated off the ventilator per day. We found that all 4 patients have tolerated paced breathing independent of mechanical ventilation, with 1 patient achieving 24 hours of tracheostomy collar. CONCLUSIONS: From this study, intercostal to phrenic nerve transfer seems to be a promising approach in reducing or eliminating ventilator support in patients with C3 to C5 high spinal cord injury.

Asunto(s)

Diafragma/inervación , Nervios Intercostales/trasplante , Transferencia de Nervios/métodos , Paraplejía/complicaciones , Nervio Frénico/cirugía , Insuficiencia Respiratoria/cirugía , Traumatismos de la Médula Espinal/complicaciones , Adulto , Vértebras Cervicales , Estudios de Seguimiento , Humanos , Masculino , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Resultado del Tratamiento

RESUMEN

Shoulder surgery can result in significant postoperative pain. Interscalene brachial plexus blocks (ISBs) constitute the current criterion standard for analgesia but may be contraindicated in patients with pulmonary pathology due to the inherent risk of phrenic nerve block and symptomatic hemidiaphragmatic paralysis. Although ultrasound-guided ISB with small volumes (5 mL), dilute local anesthetic (LA) concentrations, and LA injection 4 mm lateral to the brachial plexus have been shown to reduce the risk of phrenic nerve block, no single intervention can decrease its incidence below 20%. Ultrasound-guided supraclavicular blocks with LA injection posterolateral to the brachial plexus may anesthetize the shoulder without incidental diaphragmatic dysfunction, but further confirmatory trials are required. Ultrasound-guided C7 root blocks also seem to offer an attractive, diaphragm-sparing alternative to ISB. However, additional large-scale studies are needed to confirm their efficacy and to quantify the risk of periforaminal vascular breach. Combined axillary-suprascapular nerve blocks may provide adequate postoperative analgesia for minor shoulder surgery but do not compare favorably to ISB for major surgical procedures. One intriguing solution lies in the combined use of infraclavicular brachial plexus blocks and suprascapular nerve blocks. Theoretically, the infraclavicular approach targets the posterior and lateral cords, thus anesthetizing the axillary nerve (which supplies the anterior and posterior shoulder joint), as well as the subscapular and lateral pectoral nerves (both of which supply the anterior shoulder joint), whereas the suprascapular nerve block anesthetizes the posterior shoulder. Future randomized trials are required to validate the efficacy of combined infraclavicular-suprascapular blocks for shoulder surgery.

Asunto(s)

Anestésicos Locales/administración & dosificación , Plexo Braquial/cirugía , Diafragma , Bloqueo Nervioso/métodos , Articulación del Hombro/cirugía , Ultrasonografía Intervencional/métodos , Plexo Braquial/diagnóstico por imagen , Plexo Braquial/efectos de los fármacos , Diafragma/efectos de los fármacos , Diafragma/inervación , Humanos , Dolor Postoperatorio/diagnóstico por imagen , Dolor Postoperatorio/prevención & control , Articulación del Hombro/diagnóstico por imagen , Articulación del Hombro/efectos de los fármacos

RESUMEN

PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

Asunto(s)

Bupivacaína/análogos & derivados , Bloqueo Neuromuscular , Unión Neuromuscular/efectos de los fármacos , Pancuronio/farmacología , Transmisión Sináptica/efectos de los fármacos , Anestésicos Locales/farmacología , Animales , Bupivacaína/farmacología , Diafragma/efectos de los fármacos , Diafragma/inervación , Quimioterapia Combinada , Estimulación Eléctrica/métodos , Levobupivacaína , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Modelos Animales , Unión Neuromuscular/fisiología , Fármacos Neuromusculares no Despolarizantes/farmacología , Ratas Wistar , Transmisión Sináptica/fisiología

RESUMEN

ABSTRACT PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

Asunto(s)

Animales , Masculino , Pancuronio/farmacología , Bupivacaína/análogos & derivados , Transmisión Sináptica/efectos de los fármacos , Bloqueo Neuromuscular , Unión Neuromuscular/efectos de los fármacos , Bupivacaína/farmacología , Diafragma/efectos de los fármacos , Diafragma/inervación , Ratas Wistar , Fármacos Neuromusculares no Despolarizantes/farmacología , Transmisión Sináptica/fisiología , Modelos Animales , Quimioterapia Combinada , Estimulación Eléctrica/métodos , Anestésicos Locales/farmacología , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Unión Neuromuscular/fisiología

RESUMEN

The Kölliker-Fuse (KF) region, located in the dorsolateral pons, projects to several brainstem areas involved in respiratory regulation, including the chemoreceptor neurons within the retrotrapezoid nucleus (RTN). Several lines of evidence indicate that the pontine KF region plays an important role in the control of the upper airways for the maintenance of appropriate airflow to and from the lungs. Specifically, we hypothesized that the KF region is involved in mediating the response of the hypoglossal motor activity to central respiratory chemoreflex activation and to stimulation of the chemoreceptor neurons within the RTN region. To test this hypothesis, we combined immunohistochemistry and physiological experiments. We found that in the KF, the majority of biotinylated dextran amine (BDA)-labeled axonal varicosities contained detectable levels of vesicular glutamate transporter-2 (VGLUT2), but few contained glutamic acid decarboxylase-67 (GAD67). The majority of the RTN neurons that were FluorGold (FG)-immunoreactive (i.e., projected to the KF) contained hypercapnia-induced Fos, but did not express tyrosine hydroxylase. In urethane-anesthetized sino-aortic denervated and vagotomized male Wistar rats, hypercapnia (10% CO2) or N-methyl-d-aspartate (NMDA) injection (0.1mM) in the RTN increased diaphragm (DiaEMG) and genioglossus muscle (GGEMG) activities and elicited abdominal (AbdEMG) activity. Bilateral injection of muscimol (GABA-A agonist; 2mM) into the KF region reduced the increase in DiaEMG and GGEMG produced by hypercapnia or NMDA into the RTN. Our data suggest that activation of chemoreceptor neurons in the RTN produces a significant increase in the genioglossus muscle activity and the excitatory pathway is dependent on the neurons located in the dorsolateral pontine KF region.

Asunto(s)

Células Quimiorreceptoras/fisiología , Bulbo Raquídeo/fisiología , Puente/fisiología , Respiración , Lengua/fisiología , Animales , Células Quimiorreceptoras/citología , Diafragma/inervación , Diafragma/fisiología , Glutamato Descarboxilasa/metabolismo , Ácido Glutámico/metabolismo , Hipercapnia/patología , Hipercapnia/fisiopatología , Masculino , Bulbo Raquídeo/citología , Muscimol/farmacología , N-Metilaspartato/farmacología , Neurotransmisores/farmacología , Puente/citología , Puente/efectos de los fármacos , Ratas Wistar , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Respiración/efectos de los fármacos , Lengua/inervación , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo

RESUMEN

Huntington's disease (HD) is a neurodegenerative disorder characterized by a progressive decline of motor and cognitive functions. It is caused by a polyglutamine expansion in the huntingtin (htt) protein, which then leads to neurodegeneration that span both the central and peripheral nervous system. Previous works have shown that htt interacts with several proteins from the neurotransmitter release machinery causing synaptic dysfunction. In this work, we looked for alterations in diaphragm neuromuscular junctions (NMJs) from 3 to 4 months old BACHD mouse model for HD. This model represents a new and robust in vivo paradigm for studying the pathogenesis of HD. For optical analysis, NMJs were stained with FM1-43fx and α-bungarotoxin to visualize both pre and postsynaptic elements, respectively. Confocal microscopy optical analysis showed a decrease in the number of synaptic elements and fluorescence intensity in NMJs from BACHD diaphragms compared to WT. We next analyzed presynaptic activity and we observed that synaptic vesicle exocytosis was impaired in NMJs from BACHD diaphragms. Ultrastructural analysis revealed significant changes in the form and sizes of the synaptic vesicles in BACHD diaphragm NMJs that could contribute to impaired exocytosis. Additionally, electrophysiology recordings revealed a decrease in the amplitude of miniature endplate potentials (MEPPs) from BACHD diaphragm NMJs. Our data suggest a dysfunction in BACHD diaphragm NMJs that might occur in other muscles and may aggravate the motor defects seen in HD. These results may contribute to a better understanding of peripheral cholinergic dysfunction in this neurodegenerative disease.

Asunto(s)

Diafragma/inervación , Modelos Animales de Enfermedad , Enfermedad de Huntington/metabolismo , Unión Neuromuscular/metabolismo , Animales , Ratones

RESUMEN

Recently, we demonstrated the existence of nonextensive behavior in neuromuscular transmission (da Silva et al. in Phys Rev E 84:041925, 2011). In this letter, we first obtain a maximum-likelihood q-estimator to calculate the scale factor ([Formula: see text]) and the q-index of q-Gaussian distributions. Next, we use the indexes to analyze spontaneous miniature end plate potentials in electrophysiological recordings from neuromuscular junctions. These calculations were performed assuming both normal and high extracellular potassium concentrations [Formula: see text]. This protocol was used to test the validity of Tsallis statistics under electrophysiological conditions closely resembling physiological stimuli. The analysis shows that q-indexes are distinct depending on the extracellular potassium concentration. Our letter provides a general way to obtain the best estimate of parameters from a q-Gaussian distribution function. It also expands the validity of Tsallis statistics in realistic physiological stimulus conditions. In addition, we discuss the physical and physiological implications of these findings.

Asunto(s)

Potenciales Postsinápticos Miniatura/fisiología , Unión Neuromuscular/fisiología , Potasio/fisiología , Animales , Diafragma/inervación , Diafragma/fisiología , Funciones de Verosimilitud , Ratones , Distribución Normal , Transmisión Sináptica/fisiología

RESUMEN

INTRODUCTION: Sevoflurane and isoflurane are anesthetics that cause muscle relaxation and potentiate the effects of neuromuscular blocking agents. Their presynaptic mechanisms of action are not understood completely, especially at the motor nerve terminal. METHODS: We compared the presynaptic effects of these anesthetics on the exocytosis of synaptic vesicles labeled with the dye FM1-43 at the mouse neuromuscular junction. RESULTS: Neither anesthetic evoked spontaneous exocytosis of synaptic vesicles, but both significantly inhibited the depolarization evoked by 4-aminopyridine and veratridine, suggesting a putative action on sodium channels. Exocytosis evoked by veratridine was inhibited by tetrodotoxin alone or in conjunction with sevoflurane or isoflurane, indicating that both agents may target voltage-gated sodium channels. CONCLUSIONS: We suggest that sevoflurane and isoflurane inhibit exocytosis evoked by sodium-dependent depolarization and might act on tetrodotoxin-sensitive sodium channels. These findings contribute to a better understanding of some clinical neuromuscular effects induced by these anesthetics.

Asunto(s)

Anestésicos por Inhalación/farmacología , Isoflurano/farmacología , Éteres Metílicos/farmacología , Unión Neuromuscular/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Animales , Diafragma/efectos de los fármacos , Diafragma/inervación , Diafragma/fisiología , Femenino , Ratones , Unión Neuromuscular/fisiología , Terminales Presinápticos/fisiología , Sevoflurano

Asunto(s)

Terapia por Estimulación Eléctrica/instrumentación , Hipoventilación/diagnóstico , Hipoventilación/terapia , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/terapia , Nervio Frénico/fisiología , Colombia , Depresión/diagnóstico , Depresión/genética , Depresión/terapia , Diafragma/inervación , Diafragma/cirugía , Complejo Dinactina , Terapia por Estimulación Eléctrica/métodos , Femenino , Humanos , Hipoventilación/genética , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Trastornos Parkinsonianos/genética , Resultado del Tratamiento

RESUMEN

Etomidate is an intravenous anesthetic used during anesthesia induction. This agent induces spontaneous movements, especially myoclonus after its administration suggesting a putative primary effect at the central nervous system or the periphery. Therefore, the aim of this study was to investigate the presynaptic and postsynaptic effects of etomidate at the mouse neuromuscular junction (NMJ). Diaphragm nerve muscle preparations were isolated and stained with the styryl dye FM1-43, a fluorescent tool that tracks synaptic vesicles exo-endocytosis that are key steps for neurotransmission. We observed that etomidate induced synaptic vesicle exocytosis in a dose-dependent fashion, an effect that was independent of voltage-gated Na(+) channels. By contrast, etomidate-evoked exocytosis was dependent on extracellular Ca(2+) because its effect was abolished in Ca(2+)-free medium and also inhibited by omega-Agatoxin IVA (30 and 200nM) suggesting the participation of P/Q-subtype Ca(2+) channels. Interestingly, even though etomidate induced synaptic vesicle exocytosis, we did not observe any significant difference in the frequency and amplitude of miniature end-plate potentials (MEPPs) in the presence of the anesthetic. We therefore investigated whether etomidate could act on nicotinic acetylcholine receptors labeled with α-bungarotoxin-Alexa 594 and we observed less fluorescence in preparations exposed to the anesthetic. In conclusion, our results suggest that etomidate exerts a presynaptic effect at the NMJ inducing synaptic vesicle exocytosis, likely through the activation of P-subtype voltage gated Ca(2+) channels without interfering with MEPPs frequency. The present data contribute to a better understanding about the effect of etomidate at the neuromuscular synapse and may help to explain some clinical effects of this agent.

Asunto(s)

Etomidato/farmacología , Potenciales Evocados/efectos de los fármacos , Exocitosis/efectos de los fármacos , Hipnóticos y Sedantes/farmacología , Placa Motora/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Vesículas Sinápticas/efectos de los fármacos , Animales , Canales de Calcio Tipo P/efectos de los fármacos , Canales de Calcio Tipo P/metabolismo , Canales de Calcio Tipo Q/efectos de los fármacos , Canales de Calcio Tipo Q/metabolismo , Diafragma/efectos de los fármacos , Diafragma/inervación , Relación Dosis-Respuesta a Droga , Femenino , Ratones , Receptores Nicotínicos/efectos de los fármacos

RESUMEN

BACKGROUND AND PURPOSE: The role of inosine at the mammalian neuromuscular junction (NMJ) has not been clearly defined. Moreover, inosine was classically considered to be the inactive metabolite of adenosine. Hence, we investigated the effect of inosine on spontaneous and evoked ACh release, the mechanism underlying its modulatory action and the receptor type and signal transduction pathway involved. EXPERIMENTAL APPROACH: End-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) were recorded from the mouse phrenic-nerve diaphragm preparations using conventional intracellular electrophysiological techniques. KEY RESULTS: Inosine (100 µM) reduced MEPP frequency and the amplitude and quantal content of EPPs; effects inhibited by the selective A3 receptor antagonist MRS-1191. Immunohistochemical assays confirmed the presence of A3 receptors at mammalian NMJ. The voltage-gated calcium channel (VGCC) blocker Cd(2+) , the removal of extracellular Ca(2+) and the L-type and P/Q-type VGCC antagonists, nitrendipine and ω-agatoxin IVA, respectively, all prevented inosine-induced inhibition. In the absence of endogenous adenosine, inosine decreased the hypertonic response. The effects of inosine on ACh release were prevented by the Gi/o protein inhibitor N-ethylmaleimide, PKC antagonist chelerytrine and calmodulin antagonist W-7, but not by PKA antagonists, H-89 and KT-5720, or the inhibitor of CaMKII KN-62. CONCLUSION AND IMPLICATIONS: Our results suggest that, at motor nerve terminals, inosine induces presynaptic inhibition of spontaneous and evoked ACh release by activating A3 receptors through a mechanism that involves L-type and P/Q-type VGCCs and the secretory machinery downstream of calcium influx. A3 receptors appear to be coupled to Gi/o protein. PKC and calmodulin may be involved in these effects of inosine.

Asunto(s)

Acetilcolina/metabolismo , Inosina/farmacología , Unión Neuromuscular/efectos de los fármacos , Receptor de Adenosina A3/efectos de los fármacos , Animales , Bloqueadores de los Canales de Calcio/farmacología , Carbazoles/farmacología , Diafragma/inervación , Dihidropiridinas/farmacología , Etilmaleimida/farmacología , Femenino , Masculino , Ratones , Unión Neuromuscular/metabolismo , Nervio Frénico , Pirroles/farmacología , Receptor de Adenosina A3/metabolismo , Receptores Purinérgicos P1

RESUMEN

BACKGROUND: Autonomic imbalance, characterized by sympathetic hyperactivity and diminished vagal tone, is a known mechanism for essential hypertension. Inspiratory muscle training (IMT) demonstrates beneficial outcomes in a number of cardiovascular populations, which may potentially extend to patients with hypertension. The aim of this study was to further elucidate the effects of IMT on blood pressure and autonomic cardiovascular control in patients with essential hypertension. METHODS: Thirteen patients with hypertension were randomly assigned to an eight-week IMT program (6 patients) or to a placebo-IMT (P-IMT, 7 patients) protocol. We recorded RR interval for posterior analysis of heart rate variability and blood pressure, by ambulatory blood pressure monitoring (ABPM), before and after the program. RESULTS: There was a significant increase in inspiratory muscle strength in the IMT group (82.7 ± 28.8 vs 121.5 ± 21.8 cmH2O, P<0.001), which was not demonstrated by P-IMT (93.3 ± 25.3 vs 106.1 ± 25.3 cmH2O, P>0.05). There was also a reduction in 24-hour measurement of systolic (133.2 ± 9.9 vs 125.2 ± 13.0 mm Hg, P=0.02) and diastolic (80.7 ± 12.3 vs 75.2 ± 1.0 mm Hg, P=0.02) blood pressure, as well as in daytime systolic (136.8 ± 12.2 vs 127.6 ± 14.2 mm Hg, P=0.008) and diastolic (83.3 ± 13.1 vs. 77.2 ± 12.2 mm Hg, P =0.01) blood pressure in the IMT group. In relation to autonomic cardiovascular control, we found increased parasympathetic modulation (HF: 75.5 ± 14.6 vs. 84.74 ± 7.55 n.u, P=0.028) and reduced sympathetic modulation (LF: 34.67 ± 20.38 vs. 12.81 ± 6.68 n.u; P=0.005). Moreover, there was reduction of cardiac sympathetic discharge (fLF) in IMT group (P=0.01). CONCLUSIONS: IMT demonstrates beneficial effects on systolic and diastolic blood pressure as well as autonomic cardiovascular control in hypertensive patients.

Asunto(s)

Presión Sanguínea/fisiología , Ejercicios Respiratorios/métodos , Diafragma/fisiología , Hipertensión/terapia , Inhalación/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Anciano , Diafragma/inervación , Método Doble Ciego , Hipertensión Esencial , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos

RESUMEN

OBJECTIVE: Patients with high cervical spinal cord injury are usually dependent on mechanical ventilation support, which, albeit life saving, is associated with complications and decreased life expectancy because of respiratory infections. Diaphragm pacing stimulation (DPS), sometimes referred to as electric ventilation, induces inhalation by stimulating the inspiratory muscles. Our objective was to highlight the indications for and some aspects of the surgical technique employed in the laparoscopic insertion of the DPS electrodes, as well as to describe five cases of tetraplegic patients submitted to the technique. METHODS: Patient selection involved transcutaneous phrenic nerve studies in order to determine whether the phrenic nerves were preserved. The surgical approach was traditional laparoscopy, with four ports. The initial step was electrical mapping in order to locate the "motor points" (the points at which stimulation would cause maximal contraction of the diaphragm). If the diaphragm mapping was successful, four electrodes were implanted into the abdominal surface of the diaphragm, two on each side, to stimulate the branches of the phrenic nerve. RESULTS: Of the five patients, three could breathe using DPS alone for more than 24 h, one could do so for more than 6 h, and one could not do so at all. CONCLUSIONS: Although a longer follow-up period is needed in order to reach definitive conclusions, the initial results have been promising. At this writing, most of our patients have been able to remain ventilator-free for long periods of time.

Asunto(s)

Diafragma/inervación , Terapia por Estimulación Eléctrica/métodos , Parálisis Respiratoria/terapia , Traumatismos de la Médula Espinal/complicaciones , Adolescente , Adulto , Femenino , Humanos , Neuroestimuladores Implantables , Masculino , Parálisis Respiratoria/etiología , Resultado del Tratamiento , Desconexión del Ventilador/métodos , Adulto Joven