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Scientific Reports May 2024About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated... (Comparative Study)
Comparative Study
About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated with delayed weaning and increased mortality. Inducing active diaphragmatic contraction via electrical phrenic nerve stimulation (PNS) not only provides the potential to reduce diaphragmatic muscular atrophy but also generates physiological-like ventilation and therefore offers a promising alternative to MV. Reasons why PNS is not yet used in critical care medicine are high procedural invasiveness, insufficient evidence, and lack of side-by-side comparison to MV. This study aims to establish a minimal-invasive percutaneous, bilateral electrode placement approach for sole PNS breathing and thereby enable, for the first time, a breath-by-breath comparison to MV. Six juvenile German Landrace pigs received general anesthesia and orotracheal intubation. Following the novel ultrasound-guided, landmark-based, 4-step approach, two echogenic needles per phrenic nerve were successfully placed. Stimulation effectiveness was evaluated measuring tidal volume, diaphragmatic thickening and tomographic electrical impedance in a breath-by-breath comparison to MV. Following sufficient bilateral phrenic nerve stimulation in all pigs, PNS breaths showed a 2.2-fold increase in diaphragmatic thickening. It induced tidal volumes in the lung-protective range by negative pressure inspiration and improved dorso-caudal regional ventilation in contrast to MV. Our study demonstrated the feasibility of a novel ultrasound-guided, percutaneous phrenic nerve stimulation approach, which generated sufficient tidal volumes and showed more resemblance to physiological breathing than MV in a breath-by-breath comparison.
Topics: Animals; Phrenic Nerve; Respiration, Artificial; Swine; Pilot Projects; Diaphragm; Tidal Volume; Electric Stimulation Therapy; Transcutaneous Electric Nerve Stimulation; Electric Stimulation
PubMed: 38704459
DOI: 10.1038/s41598-024-61103-5 -
Seminars in Vascular Surgery Mar 2024Surgical decompression of the thoracic outlet, along with treatment of the involved nerve or vessel, is the accepted treatment modality when indicated. Although... (Review)
Review
Surgical decompression of the thoracic outlet, along with treatment of the involved nerve or vessel, is the accepted treatment modality when indicated. Although neurogenic thoracic outlet syndrome (TOS) is often operated via the axillary approach and venous TOS via the paraclavicular approach, arterial TOS is almost always operated via the supraclavicular approach. The supraclavicular approach provides excellent access to the artery, brachial plexus, phrenic nerve, and the cervical and/or first ribs, along with any bony or fibrous or muscular abnormality that may be causing compression of the neurovascular structures. Even for neurogenic TOS, for which the axillary approach offers good cosmesis, the supraclavicular approach helps with adequate decompression while preserving the first rib. This approach may also be sufficient for thin patients with venous TOS. For arterial TOS, a supraclavicular incision usually suffices for excision of bony abnormality and repair of the subclavian artery.
Topics: Humans; Thoracic Outlet Syndrome; Decompression, Surgical; Treatment Outcome; Subclavian Artery
PubMed: 38704185
DOI: 10.1053/j.semvascsurg.2024.01.006 -
Europace : European Pacing,... May 2024Pulsed field ablation (PFA) for the treatment of atrial fibrillation (AF) potentially offers improved safety and procedural efficiencies compared with thermal ablation.... (Clinical Trial)
Clinical Trial
AIMS
Pulsed field ablation (PFA) for the treatment of atrial fibrillation (AF) potentially offers improved safety and procedural efficiencies compared with thermal ablation. Opportunities remain to improve effective circumferential lesion delivery, safety, and workflow of first-generation PFA systems. In this study, we aim to evaluate the initial clinical experience with a balloon-in-basket, 3D integrated PFA system with a purpose-built form factor for pulmonary vein (PV) isolation.
METHODS AND RESULTS
The VOLT CE Mark Study is a pre-market, prospective, multi-centre, single-arm study to evaluate the safety and effectiveness of the Volt™ PFA system for the treatment of paroxysmal (PAF) or persistent AF (PersAF). Feasibility sub-study subjects underwent phrenic nerve evaluation, endoscopy, chest computed tomography, and cerebral magnetic resonance imaging. Study endpoints were the rate of primary serious adverse event within 7 days and acute procedural effectiveness. A total of 32 subjects (age 61.6 ± 9.6 years, 65.6% male, 84.4% PAF) were enrolled and treated in the feasibility sub-study and completed a 30-day follow-up. Acute effectiveness was achieved in 99.2% (127/128) of treated PVs (96.9% of subjects, 31/32) with 23.8 ± 4.2 PFA applications/subject. Procedure, fluoroscopy, LA dwell, and transpired ablation times were 124.6 ± 28.1, 19.8 ± 8.9, 53.0 ± 21.0, and 48.0 ± 19.9 min, respectively. Systematic assessments of initial safety revealed no phrenic nerve injury, pulmonary vein stenosis, or oesophageal lesions causally related to the PFA system and three subjects with silent cerebral lesions (9.4%). There were no primary serious adverse events.
CONCLUSION
The initial clinical use of the Volt PFA System demonstrates acute safety and effectiveness in the treatment of symptomatic, drug refractory AF.
Topics: Humans; Male; Female; Feasibility Studies; Atrial Fibrillation; Middle Aged; Pulmonary Veins; Treatment Outcome; Prospective Studies; Catheter Ablation; Aged; Equipment Design; Phrenic Nerve; Time Factors
PubMed: 38701222
DOI: 10.1093/europace/euae118 -
Annals of Anatomy = Anatomischer... Jun 2024The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve. (Review)
Review
OBJECTIVE
The aim of this systematic review is to study the subdiaphragmatic anatomy of the phrenic nerve.
MATERIALS AND METHODS
A computerised systematic search of the Web of Science database was conducted. The key terms used were phrenic nerve, subdiaphragmat*, esophag*, liver, stomach, pancre*, duoden*, intestin*, bowel, gangli*, biliar*, Oddi, gallbladder, peritone*, spleen, splenic, hepat*, Glisson, falciform, coronary ligament, kidney, suprarenal, and adrenal. The 'cited-by' articles were also reviewed to ensure that all appropriate studies were included.
RESULTS
A total of one thousand three hundred and thirty articles were found, of which eighteen met the inclusion and exclusion criteria. The Quality Appraisal for Cadaveric Studies scale revealed substantial to excellent methodological quality of human studies, while a modified version of the Systematic Review Centre for Laboratory Animal Experimentation Risk of Bias Tool denoted poor methodological quality of animal studies. According to human studies, phrenic supply has been demonstrated for the gastro-esophageal junction, stomach, celiac ganglia, liver and its coronary ligament, inferior vena cava, gallbladder and adrenal glands, with half of the human samples studied presenting phrenic nerve connections with any subdiaphragmatic structure.
CONCLUSIONS
This review provides the first systematic evidence of subdiaphragmatic phrenic nerve supply and connections. This is of interest to professionals who care for people suffering from neck and shoulder pain, as well as patients with peridiaphragmatic disorders or hiccups. However, there are controversies about the autonomic or sensory nature of this supply.
Topics: Phrenic Nerve; Humans; Diaphragm; Animals
PubMed: 38692333
DOI: 10.1016/j.aanat.2024.152269 -
Journal of Neurophysiology Jun 2024Prolonged inhibition of respiratory neural activity elicits a long-lasting increase in phrenic nerve amplitude once respiratory neural activity is restored. Such...
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. 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.
Topics: Animals; Phrenic Nerve; Protein Kinase C; Rats, Sprague-Dawley; Motor Neurons; Male; Rats; Neuronal Plasticity
PubMed: 38691529
DOI: 10.1152/jn.00138.2024 -
Biomedicines Apr 2024Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia...
Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats ( = 24; weight: 280-360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, = 6; isoflurane group, = 6) and a control group (urethane group, = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO = 0.09), separated by 3 min recovery intervals at FiO = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia.
PubMed: 38672264
DOI: 10.3390/biomedicines12040910 -
BioRxiv : the Preprint Server For... Apr 2024Impaired diaphragm activation contributes to morbidity and mortality in many neurodegenerative diseases and neurologic injuries. We conducted experiments to determine if...
Impaired diaphragm activation contributes to morbidity and mortality in many neurodegenerative diseases and neurologic injuries. We conducted experiments to determine if expression of an excitatory DREADD (designer receptors exclusively activation by designer drugs) in the mid-cervical spinal cord would enable respiratory-related activation of phrenic motoneurons to increase diaphragm activation. Wild type (C57/bl6) and ChAT-Cre mice received bilateral intraspinal (C4) injections of an adeno-associated virus (AAV) encoding the hM3D(Gq) excitatory DREADD. In wild type mice, this produced non-specific DREADD expression throughout the mid-cervical ventral horn. In ChAT-Cre mice, a Cre-dependent viral construct was used to drive DREADD expression in C4 ventral horn motoneurons, targeting the phrenic motoneuron pool. Diaphragm EMG was recorded during spontaneous breathing at 6-8 weeks post-AAV delivery. The selective DREADD ligand JHU37160 (J60) caused a bilateral, sustained (>1 hr) increase in inspiratory EMG bursting in both groups; the relative increase was greater in ChAT-Cre mice. Additional experiments in a ChAT-Cre rat model were conducted to determine if spinal DREADD activation could increase inspiratory tidal volume (VT) during spontaneous breathing without anesthesia. Three to four months after intraspinal (C4) injection of AAV driving Cre-dependent hM3D(Gq) expression, intravenous J60 resulted in a sustained (>30 min) increase in VT assessed using whole-body plethysmography. Subsequently, direct nerve recordings confirmed that J60 evoked a >50% increase in inspiratory phrenic output. The data show that mid-cervical spinal DREADD expression targeting the phrenic motoneuron pool enables ligand-induced, sustained increases in the neural drive to the diaphragm. Further development of this technology may enable application to clinical conditions associated with impaired diaphragm activation and hypoventilation.
PubMed: 38659846
DOI: 10.1101/2024.04.12.589188 -
Cureus Mar 2024This case report describes a rare instance of left-sided congenital pericardial agenesis (CPA) encountered during coronary artery bypass grafting (CABG) in a 77-year-old...
This case report describes a rare instance of left-sided congenital pericardial agenesis (CPA) encountered during coronary artery bypass grafting (CABG) in a 77-year-old male. In this unique case, the presence of an unusual strip of left pericardium containing the phrenic nerve posed significant surgical challenges. Special attention was required for the graft lay, ensuring adequate filling of the heart during assessment before closure, as well as emphasis on the need for generous graft length. Additionally, the evaluation of graft positioning prior to cardiopulmonary bypass was crucial. Despite these complexities, CABG was successfully performed with no complications to note. This case underscores the importance of adaptability in surgical technique to manage the unique challenges posed by CPA, leading to a positive outcome despite the atypical cardiac anatomy.
PubMed: 38659528
DOI: 10.7759/cureus.56885 -
Pneumologie (Stuttgart, Germany) Jun 2024The causes of diaphragmatic paresis are manifold. An association between neuralgic amyotrophy (NA) and hepatitis E virus (HEV) infection has been reported. We wondered... (Review)
Review
INTRODUCTION
The causes of diaphragmatic paresis are manifold. An association between neuralgic amyotrophy (NA) and hepatitis E virus (HEV) infection has been reported. We wondered about the prevalence of diaphragmatic disfunction and hepatitis E infection in our clinic.
METHODS
From July 1st, 2020 to August 31st, 2023, patients presenting with diaphragmatic dysfunction and simultaneous clinical symptoms of an acute NA, or a history of NA, as well as patients with previously unexplained diaphragmatic dysfunction were examined for HEV infection.
RESULTS
By August 31st, 2023, 13 patients with diaphragmatic dysfunction and HEV infection were diagnosed (4 women, 9 men). Mean age was 59 ± 10 years. Liver values were normal in all patients. The median latency to diagnosis was five months (range: 1-48 months); nine patients, 4 of them with typical symptoms of NA, presented with acute onset three patients showed bilateral diaphragmatic dysfunction. All patients had a positive IgG immunoblot. Seven patients, three with NA, had an elevated hepatitis E IgM titer and six of them also a positive IgM immunoblot. In all cases, O2C hepatitis genotype 3 was identified. In eight cases, all those with a high IgG titer >125, the O2 genotype 1 was also detected.
CONCLUSION
NA that shows involvement of the phrenic nerve resulting in diaphragmatic dysfunction and dyspnoea, may be associated with HEV infection. The observation of 13 patients with diaphragmatic dysfunctions and HEV infection within a period of three years indicates a high number of undetected HEV-associated diaphragmatic dysfunction in the population, especially in the absence of NA symptoms. Therefore, even in diaphragmatic dysfunction without NA symptoms and causative damaging event, HEV infection should be considered, as it may represent a subform of NA with only phrenic nerve involvement. Therapy of HEV-associated diaphragmatic dysfunction in the acute phase is an open question. In view of the poor prognosis for recovery, antiviral therapy should be discussed. However, no relevant data are currently available.
Topics: Aged; Female; Humans; Male; Middle Aged; Brachial Plexus Neuritis; Diaphragm; Hepatitis E; Respiratory Paralysis
PubMed: 38657646
DOI: 10.1055/a-2291-0560 -
Journal of the Neurological Sciences May 2024Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa...
BACKGROUND
Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients.
MATERIAL AND METHODS
A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed.
RESULTS
Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited.
CONCLUSIONS
Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.
Topics: Humans; Glycogen Storage Disease Type II; Male; Diaphragm; Female; Middle Aged; Muscle Weakness; Phrenic Nerve; Motor Neurons; Adult; Electromyography; Neural Conduction; Muscle Fibers, Skeletal; Aged; Respiratory Insufficiency; Prospective Studies; Action Potentials
PubMed: 38653115
DOI: 10.1016/j.jns.2024.123021