Inspiratory response and side-effects to rapid bilateral magnetic phrenic nerve stimulation using differently shaped coils: implications for stimulation-assisted mechanical ventilation.

BACKGROUND: Rapid magnetic stimulation (RMS) of the phrenic nerves may serve to attenuate diaphragm atrophy during mechanical ventilation. With different coil shapes and stimulation location, inspiratory responses and side-effects may differ. This study aimed to compare the inspiratory and sensory responses of three different RMS-coils either used bilaterally on the neck or on the chest, and to determine if ventilation over 10 min can be achieved without muscle fatigue and coils overheating. METHODS: Healthy participants underwent bilateral anterior 1-s RMS on the neck (RMSBAMPS) (N = 14) with three different pairs of magnetic coils (parabolic, D-shape, butterfly) at 15, 20, 25 and 30 Hz stimulator-frequency and 20% stimulator-output with + 10% increments. The D-shape coil with individual optimal stimulation settings was then used to ventilate participants (N = 11) for up to 10 min. Anterior RMS on the chest (RMSaMS) (N = 8) was conducted on an optional visit. Airflow was assessed via pneumotach and transdiaphragmatic pressure via oesophageal and gastric balloon catheters. Perception of air hunger, pain, discomfort and paresthesia were measured with a numerical scale. RESULTS: Inspiration was induced via RMSBAMPS in 86% of participants with all coils and via RMSaMS in only one participant with the parabolic coil. All coils produced similar inspiratory and sensory responses during RMSBAMPS with the butterfly coil needing higher stimulator-output, which resulted in significantly larger discomfort ratings at maximal inspiratory responses. Ten of 11 participants achieved 10 min of ventilation without decreases in minute ventilation (15.7 ± 4.6 L/min). CONCLUSIONS: RMSBAMPS was more effective than RMSaMS, and could temporarily ventilate humans seemingly without development of muscular fatigue. Trial registration This study was registered on clinicaltrials.gov (NCT04176744).

Ultrafast ultrasound coupled with cervical magnetic stimulation for non-invasive and non-volitional assessment of diaphragm contractility.

KEY POINTS: Twitch transdiaphragmatic pressure elicited by cervical magnetic stimulation of the phrenic nerves is a fully non-volitional method for assessing diaphragm contractility in humans, yet it requires invasive procedures such as oesophageal and gastric catheter balloons.  Ultrafast ultrasound enables a very high frame rate allowing the capture of transient events, such as muscle contraction elicited by nerve stimulation (twitch). Whether indices derived from ultrafast ultrasound can be used as an alternative to the invasive measurement of twitch transdiaphragmatic pressure is unknown.  Our findings demonstrate that maximal diaphragm tissue velocity assessed using ultrafast ultrasound following cervical magnetic stimulation is reliable, sensitive to change in cervical magnetic stimulation intensity, and correlates to twitch transdiaphragmatic pressure.  This approach provides a novel fully non-invasive and non-volitional tool for the assessment of diaphragm contractility in humans. ABSTRACT: Measuring twitch transdiaphragmatic pressure (Pdi,tw ) elicited by cervical magnetic stimulation (CMS) is considered as a reference method for the standardized evaluation of diaphragm function. Yet, the measurement of Pdi requires invasive oesophageal and gastric catheter-balloons. Ultrafast ultrasound is a non-invasive imaging technique enabling frame rates high enough to capture transient events such as evoked muscle contractions. This study investigated relationships between indices derived from ultrafast ultrasound and Pdi,tw , and how these indices might be used to estimate Pdi,tw . CMS was performed in 13 healthy volunteers from 30% to 100% of maximal stimulator intensity in units of 10% in a randomized order. Pdi,tw was measured and the right hemidiaphragm was imaged using a custom ultrafast ultrasound sequence with 1 kHz framerate. Maximal diaphragm axial velocity (Vdi ,max ) and diaphragm thickening fraction (TFdi,tw ) were computed. Intra-session reliability was assessed. Repeated-measures correlation (R) and Spearman correlation coefficients (ρ) were used to assess relationships between variables. Intra-session reliability was strong for Pdi,tw and Vdi,max and moderate for TFdi,tw . Vdi,max correlated with Pdi,tw in all subjects (0.64 < ρ < 1.00, R = 0.75; all P < 0.05). TFdi,tw correlated with Pdi,tw in eight subjects only (0.85 < ρ < 0.93, R = 0.69; all P < 0.05). Coupling ultrafast ultrasound and CMS shows promise for the non-invasive and fully non-volitional assessment of diaphragm contractility. This approach opens up the prospect of both diagnosis and follow-up of diaphragm contractility in clinical populations.

Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot-Marie-Tooth disease 1A.

Diaphragm weakness in Charcot-Marie-Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT-NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH2 O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH2 O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6-2.2] vs 2.5 [2.1-3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH2 O; all P < .05). DTR inversely correlated with the CMT-NSv2 score (r = -.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.

The nature of respiratory muscle weakness in patients with late-onset Pompe disease.

Late-onset Pompe disease (LOPD) causes myopathy of skeletal and respiratory muscles, and phrenic nerve pathology putatively contributes to diaphragm weakness. The aim of this study was to investigate neural contributions to diaphragm dysfunction, usefulness of diaphragm ultrasound, and involvement of expiratory abdominal muscles in LOPD. Thirteen patients with LOPD (7 male, 51±17 years) and 13 age- and gender-matched controls underwent respiratory muscle strength testing, ultrasound evaluation of diaphragm excursion and thickness, cortical and cervical magnetic stimulation (MS) of the diaphragm with simultaneous recording of surface electromyogram and twitch transdiaphragmatic pressure (twPdi; n = 6), and MS of the abdominal muscles with recording of twitch gastric pressure (twPgas; n = 6). The following parameters were significantly reduced in LOPD patients versus controls: forced vital capacity (p<0.01), maximum inspiratory and expiratory pressure (both p<0.001), diaphragm excursion velocity (p<0.05), diaphragm thickening ratio (1.8 ±â€¯0.4 vs. 2.6 ±â€¯0.6, p<0.01), twPdi following cervical MS (12.0 ±â€¯6.2 vs. 19.4 ±â€¯4.8 cmH2O, p<0.05), and twPgas following abdominal muscle stimulation (8.8 ±â€¯8.1 vs. 34.6 ±â€¯17.1 cmH2O, p<0.01). Diaphragm motor evoked potentials and compound muscle action potentials showed no between-group differences. In conclusion, phrenic nerve involvement in LOPD could not be electrophysiologically confirmed. Ultrasound supports assessment of diaphragm function. Abdominal expiratory muscles are functionally involved in LOPD.

Assessment of Central Drive to the Diaphragm by Twitch Interpolation: Normal Values, Theoretical Considerations, and Future Directions.

BACKGROUND: The twitch interpolation technique is a promising tool for assessing central drive to the diaphragm. It is used to quantify the degree of voluntary diaphragm activation during predefined breathing maneuvers. OBJECTIVES: This study was designed to (a) determine reference values for the level of voluntary activation of the diaphragm using the twitch occlusion technique in healthy adults and (b) explore the association between central drive to the diaphragm and volitional tests of respiratory muscle strength. METHODS: Twenty-seven healthy volunteers aged 26 ± 14 years (18 male) were enrolled. Twitch transdiaphragmatic pressure (Pdi) was determined at relaxed functional residual capacity in response to cervical magnetic stimulation (CMS) of the phrenic nerves. The subjects were then instructed to gradually increase voluntary activation of the diaphragm, and the effects of superimposed magnetic stimuli on voluntary Pdi were assessed. RESULTS: The twitch Pdi amplitude following CMS linearly decreased with increasing inspiratory effort. The resulting diaphragm voluntary activation index (DVAI) during maximal voluntary contraction was 75 ± 15% irrespective of gender or age. Twitch duration, half relaxation time, and area under the curve of superimposed Pdi deflections did not show a linear but an exponential association with increasing voluntary activation of the diaphragm. More than 2/3 of the decrease in the above values was evident after 1/3 of voluntary diaphragm contraction. Forced vital capacity (FVC) was inversely correlated with the DVAI. CONCLUSIONS: Twitch interpolation allows for assessment of central drive to the diaphragm. The maximum DVAI is independent of gender or age, and significantly related to FVC but not to maximum inspiratory pressure or Pdi as direct measures of diaphragm strength.

The Effects of Phrenic Nerve Degeneration by Axotomy and Crush on the Electrical Activities of Diaphragm Muscles of Rats.

The aim of this study was to investigate the effect of axotomy and crush-related degeneration on the electrical activities of diaphragm muscle strips of experimental rats. In the present study, twenty-one male Wistar-albino rats were used and divided into three groups. The animals in the first group were not crushed or axotomized and served as controls. Phrenic nerves of the rats in the second and third groups were crushed or axotomized in the diaphragm muscle. Resting membrane potential (RMP) was decreased significantly in both crush and axotomy of diaphragm muscle strips of experimental rats (p < 0.05). Depolarization time (T DEP) and half-repolarization (1/2 RT) time were significantly prolonged in crush and axotomy rats (p < 0.05). Crushing or axotomizing the phrenic nerves may produce electrical activities in the diaphragm muscle of the rat by depolarization time and half-repolarization time prolonged in crush and axotomy rats.

Morfofisiologia da inervação do diafragma de ovinos / Morphophysiology of diaphragm innervation in sheep

Thirty diaphragms of sheep of Santa Inês breed were studied regarding their origin, division and arrangement of the right and left phrenic nerves (Fde), and the participation of other nerves in the innervation of the diaphragm. By fixing and dissecting pieces, it was found that phrenic nerves (F) frequently come from the ventral branches of the 5th (C5) and 6th (C6) cervical spinal nerves (Ec), at right (46.67 percent) and at left (43.33 percent). The F often form a lumbocostal trunk, sternal branches at right (40.00 percent) and lumbar, costal and esternal branches at left (36.68 percent). The lumbar branches of F innervate frequently at left (96.67 percent) the homolateral pillar of the diaphragma, and at right (50.00 percent) they give fillets to Vena cava caudalis. The costal branches of the F innervate at left (90.00 percent) and at right (76.66 percent) the dorsal and ventral regions of the pars costalis. The sternal branches of the F innervate at right (100.00 percent) and at left (83.33 percent) the pars sternalis and the ventral region of the pars costalis at the same side. The intercostal nerves (VII to XII pairs, 63.33 percent) contribute to innervate the diaphragm of Santa Inês sheep.

Foram estudados em 30 diafragmas de ovinos da raça Santa Inês, a origem, a divisão e a distribuição dos nervos frênicos direito e esquerdo (Fde) e a participação de outros nervos na inervação do diafragma. Mediante fixação e dissecação das peças foi observado que os nervos frênicos (F) originam-se a partir dos ramos ventrais do 5º (C5) e 6º (C6) nervos espinhais cervicais (Ec) tanto à direita (46,67 por cento) como à esquerda (43,33 por cento). Os F finalizam em tronco lombocostal e ramo esternal à direita (40,00 por cento) e em ramo lombar, costal e esternal à esquerda (36,68 por cento). Os ramos lombares dos F inervam à esquerda (96,67 por cento) o pilar homolateral do diafragma e, à direita (50,00 por cento) fornecem filetes à veia caudal. Os ramos costais dos F ramificam à esquerda (90,00 por cento) e à direita (76,67 por cento) as regiões dorsal e ventral da pars costalis. Os ramos esternais dos F inervam à direita (100,00 por cento) e à esquerda (83,33 por cento) a pars sternalis e a região ventral da pars costalis do mesmo lado. Os nervos intercostais (VIII ao XII pares, 63,33 por cento) contribuem na inervação do diafragma de ovinos da raça Santa Inês.

Branching and distribution of the phrenic nerves in the diaphragm of Brazilian Northeast asses (Asinus asinus) / Ramificação e distribuição dos nervos frênicos no diafragma de jumentos do Nordeste brasileiro (Asinus asinus)

The results obtained from the study of 30 diaphragms of adult asses {Asinus asinus), extracted from 15 male and 15 female animals from the Brazilian Northeastern region, allowed us to reach the following conclusions: 1) The phrenic nerves more frequently result in a lumbocostal trunk and sternal branch, either right (76.7%) or left (53.3%); symmetric disposition was registered in some pieces (43.3%); 2) The lumbar branches are destined to the corresponding crura (pars lumbalis); the right branches give small branches to the medial left crus (3.3%), to the right dorsal foliole (6.7%) and to the left dorsal foliole (3.3%), and the leftones also give small branches to the medial right crus (3.3%) to the left dorsal foliole (13.3%) and to the ventral foliole (6.7%);3) The costal branches are distributed to the dorsal region of the pars costalis of each respective side, either right or left, to the right side of the ventral region (3.3%) and to the right dorsal foliole (3.3%), and the left one to the left dorsal foliole (10.0%); 4) The sternal branches are destined to the pars sternalis and ventral region of the pars costalis at the same side; at the right side, they give small branches to the vena cava caudalis (3.3%), or to the ventral foliole (3.3%).

Mediante fixação e dissecação, foram examinadas, em 30 diafragmas de jumentos do Nordeste brasileiro (Asinusasinus), sendo 15 de machos e 15 de fêmeas, adultos, a ramificação e a distribuição dos nervos frênicos direito e esquerdo, tendo-se observado que: 1) Os nervos frênicos resolvem-se mais freqüentemente em tronco lombocostal e ramo esternal, tanto à direita (76,7%) como à esquerda (53,3%), com disposição simétrica em parte dos casos (43,3%); 2) Os ramos lombares destinam-se aos pilares correspondentes {pars lumbalis), cedendo ainda, da direita, filete nervoso ao pilar mediai esquerdo (3,3%), folíolo dorsal direito (6,7%) e folíolo ventral (3,3%) e, o da esquerda, filete nervoso ao pilar mediai direito (53,3%), folíolo dorsal esquerdo (13,3%) ou folíolo ventral (6,7%); 3) Os ramos costais distribuem-se à região dorsal da pars costatis do lado correspondente, tanto à direita como à esquerda e, ainda, à região ventral (3,3%) à direita, ao folíolo dorsal direito (3,3%) e, à esquerda, ao folíolo dorsal esquerdo (10,0%); 4) Os ramos esternais distribuem-se, do mesmo lado, à pars sternalis e região ventral da pars costalis, emitindo, ainda à direita, filete nervoso para a veia cava caudal (3,3%) ou para o folíolo ventral (3,3%).