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Journal of Neurophysiology Dec 2021Phrenic afferents project to brainstem areas responsible for cardiorespiratory control and the mid-cervical spinal cord containing the phrenic motor nucleus. Our purpose...
Phrenic afferents project to brainstem areas responsible for cardiorespiratory control and the mid-cervical spinal cord containing the phrenic motor nucleus. Our purpose was to quantify the impact of small- and large-diameter phrenic afferent activation on phrenic motor output. Anesthetized and ventilated rats received unilateral phrenic nerve stimulation while contralateral phrenic motor output and blood pressure were recorded. Twelve currents of 40-Hz inspiratory-triggered stimulation were delivered (20 s on, 5 min off) to establish current response curves. Stimulation pulse width was varied to preferentially activate large-diameter phrenic afferents (narrow pulse width) and recruit small-diameter fibers (wide pulse width). Contralateral phrenic amplitude was elevated immediately poststimulation at currents above 35 µA for wide and 70 µA for narrow pulse stimulation when compared with animals not receiving stimulation (time controls). Wide pulse width stimulation also increased phrenic burst frequency at currents ≥35 µA, caused a transient decrease in mean arterial blood pressure at currents ≥50 µA, and resulted in a small change in heart rate at 300 µA. Unilateral dorsal rhizotomy attenuated stimulation-induced cardiorespiratory responses indicating that phrenic afferent activation is required. Additional analyses compared phrenic motor amplitude with output before stimulation and showed that episodic activation of phrenic afferents with narrow pulse stimulation can induce short-term plasticity. We conclude that the activation of phrenic afferents ) enhances contralateral phrenic motor amplitude when large-diameter afferents are activated, and ) when small-diameter fibers are recruited, the amplitude response is associated with changes in burst frequency and cardiovascular parameters. Acute, inspiratory-triggered stimulation of phrenic afferents increases contralateral phrenic motor amplitude in adult rats. When small-diameter afferents are recruited, the amplitude response is accompanied by an increase in phrenic burst frequency, a transient decrease in mean arterial blood pressure, and a slight increase in heart rate. Repeated episodes of large-diameter phrenic afferent activation may also be capable of inducing short-term plasticity.
Topics: Afferent Pathways; Animals; Arterial Pressure; Blood Gas Analysis; Electrophysiological Phenomena; Female; Heart Rate; Hemodynamics; Inhalation; Male; Neuronal Plasticity; Neurons, Afferent; Phrenic Nerve; Rats; Rats, Sprague-Dawley
PubMed: 34788165
DOI: 10.1152/jn.00433.2021 -
Europace : European Pacing,... Apr 2023This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during...
OBJECTIVE
This study aimed to evaluate the feasibility of real-time visualization and mapping of the right phrenic nerve (RPN) by using intracardiac echocardiography (ICE) during atrial fibrillation (AF) ablation.
BACKGROUND
RPN injury is a complication associated with the ablation of AF. Multiple approaches are currently being used to prevent and detect RPN injuries. However, none of these approaches can directly visualize the RPN in real-time during the ablation procedure.
METHODS AND RESULTS
The RPN was detected using ICE. The RPN and its adjacent structures were analysed. The relationship between the RPN's distance from the superior vena cava (SVC) and its pacing capture threshold was quantified. The safety of SVC isolation guided by the ICE-visualized RPN was evaluated. Thirty-eight people were enrolled in this study. The RPN was visualized by ICE in 92% of patients. It ran through the space between the SVC and the mediastinal pleura and had a 'straw'-like appearance upon ICE imaging. The course of the RPN was close to the SVC (minimum 1.0 ± 0.4 mm) and the right superior pulmonary vein (minimum 14.1 ± 7.3 mm). There was a positive linear correlation between the RPN's capture threshold and its distance from the SVC (Spearman's correlation coefficient = 0.728, < 0.001). SVC isolation was guided by the RPN; none of the patients developed an RPN injury.
CONCLUSIONS
RPN can be visualized by ICE in most patients, thus providing a novel approach for the real-time detection of RPN during AF ablation.
Topics: Humans; Atrial Fibrillation; Phrenic Nerve; Vena Cava, Superior; Catheter Ablation; Echocardiography; Pulmonary Veins
PubMed: 36857524
DOI: 10.1093/europace/euad012 -
Respiratory Care May 2023Mechanical ventilation is widely used in ICU patients as a lifesaving intervention. Diaphragmatic atrophy and thinning occur from lack of contractions of the diaphragm...
BACKGROUND
Mechanical ventilation is widely used in ICU patients as a lifesaving intervention. Diaphragmatic atrophy and thinning occur from lack of contractions of the diaphragm during mechanical ventilation. It may prolong weaning and increase the risk of respiratory complications. Noninvasive electromagnetic stimulation of the phrenic nerves may ameliorate the atrophy seen with ventilation. The objective of this study was to show that noninvasive repetitive electromagnetic stimulation is safe, feasible, and effective to stimulate the phrenic nerves in both awake individuals and anesthetized patients.
METHODS
A single-center study with 10 subjects overall, 5 awake volunteers and 5 anesthetized subjects. We used a prototype electromagnetic, noninvasive, simultaneous bilateral phrenic nerve stimulation device in both groups. In the awake volunteers, we assessed time-to-first capture of the phrenic nerves and safety measures, such as pain, discomfort, dental paresthesia, and skin irritation. In the anesthetized subjects, time-to-first capture as well as tidal volumes and airway pressures at 20%, 30%, and 40% stimulation intensity were assessed.
RESULTS
Diaphragmatic capture was achieved in all the subjects within a median (range) of 1 min (1 min to 9 min 21 s) for the awake subjects and 30 s (20 s to 1 min 15 s) for the anesthetized subjects. There were no adverse or severe adverse events in either group, nor any dental paresthesia, skin irritation, or subjective pain in the stimulated area. Tidal volumes increased in all the subjects in response to simultaneous bilateral phrenic nerve stimulation and increased gradually with increasing stimulation intensity. Airway pressures corresponded to spontaneous breathing of ∼2 cm HO.
CONCLUSIONS
Noninvasive phrenic nerve stimulation can be safely performed in awake and anesthetized individuals. It was feasible and effective in stimulating the diaphragm by induction of physiologic and scalable tidal volumes with minimum positive airway pressures.
Topics: Humans; Phrenic Nerve; Feasibility Studies; Paresthesia; Respiration, Artificial; Diaphragm; Pain
PubMed: 36878642
DOI: 10.4187/respcare.10568 -
ELife Dec 2022Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm...
Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.
Topics: Animals; Mice; Motor Neurons; Respiration; Interneurons; Respiratory Rate; Cadherins; Phrenic Nerve; Homeodomain Proteins
PubMed: 36583530
DOI: 10.7554/eLife.82116 -
Journal of Evolutionary Biochemistry... 2022The review addresses modern methods of electrical stimulation used to regulate the function of external respiration in humans. The methods include abdominal functional...
The review addresses modern methods of electrical stimulation used to regulate the function of external respiration in humans. The methods include abdominal functional stimulation of respiratory muscles, diaphragmatic stimulation, phrenic nerve stimulation, epidural and transcutaneous spinal cord stimulation. The physiological rationale of their application is described along with the examples of their use in clinical practice, including stimulation parameters and electrode placement diagrams for each of the methods. We analyze the effectiveness of each of the methods in patients with respiratory muscle paresis and the features of their use depending on the level of spinal cord injury. Special attention is paid to the method of epidural spinal cord stimulation because this technique is widely used in electrophysiological studies on animal models, providing deeper insight into the spinal levels of the functional control of external respiration. The review substantiates the great potential of using the method of transcutaneous electrical spinal cord stimulation both in fundamental studies of external respiration and in clinical practice.
PubMed: 36573159
DOI: 10.1134/S0022093022060175 -
Journal of Thoracic Disease Aug 2019There is a lack of consensus in the literature regarding phrenic nerve proximity to thoracic structures at the level of the diaphragm. This study was undertaken to...
BACKGROUND
There is a lack of consensus in the literature regarding phrenic nerve proximity to thoracic structures at the level of the diaphragm. This study was undertaken to provide thoracic surgeons data on phrenic nerve location in order to reduce iatrogenic injury during invasive surgery.
METHODS
Bilateral thoracic dissection was performed on 43 embalmed human cadavers (25 males; 18 females) and data was obtained from 33 left and 40 right phrenic nerves. The site of phrenic nerve penetration into the diaphragm was identified. Calipers were used to measure the distance from each phrenic nerve to the: inferior vena cava (IVC), descending aorta, esophagus, lateral thoracic wall and anterior thoracic wall.
RESULTS
Mean thoracic diameter of male cadavers was significantly greater than that of female cadavers (P value <0.0001). There was no statistically significant difference between the distances from each phrenic nerve to visceral structures between males and females, except regarding the distance from the right phrenic nerve to the anterior thoracic wall where males exhibited significantly greater distances (P value =0.0234).
CONCLUSIONS
This study provides important data on phrenic nerve proximity to intrathoracic structures in an effort to help reduce iatrogenic injury during procedures within the thoracic cavity. Although males had a significantly larger thoracic diameter than females, the only statistically significant difference showed that the right phrenic nerve is deeper in the thoracic cavity in males. As this nerve passes closer to visceral structures it may be more susceptible to damage from pathology in surrounding vessels. This may explain the increased incidence of right phrenic nerve damage due to aortic aneurysm in males reported in the literature.
PubMed: 31559049
DOI: 10.21037/jtd.2019.07.75 -
Respiratory Physiology & Neurobiology Apr 2023We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low...
We hypothesized that activation of phrenic afferents induces diaphragm motor plasticity. In anesthetized and spontaneously breathing rats we delivered 40 Hz, low threshold (twitch and 1.5X twitch threshold), inspiratory-triggered stimulation to the left hemidiaphragm for 30 min to activate ipsilateral phrenic afferents. Diaphragm amplitude ipsilateral and contralateral to stimulation were increased for 60 min following both currents compared to time controls not receiving stimulation. Diaphragm stimulation was repeated in laminectomy controls or following a unilateral C3-C6 dorsal rhizotomy to eliminate phrenic afferent volleys. Laminectomy controls expressed neuromuscular plasticity post-stimulation. In contrast, ipsilateral and contralateral diaphragm amplitude following dorsal rhizotomy was lower than laminectomy controls and no different than time controls, suggesting diaphragm motor plasticity was not induced post-rhizotomy. Our results indicate that diaphragm stimulation induces a novel form of plasticity in the phrenic motor system which requires phrenic afferent activation. Respiratory motor plasticity elicited by diaphragm stimulation may have value as a therapeutic strategy to improve diaphragm output in neuromuscular conditions.
Topics: Rats; Animals; Diaphragm; Thorax; Respiration; Phrenic Nerve; Electric Stimulation
PubMed: 36642318
DOI: 10.1016/j.resp.2023.104014 -
Physiological Reports Jan 2023Diaphragm muscle (DIAm) motor units comprise a phrenic motor neuron (PhMN), the phrenic nerve and the muscle fibers innervated, with the size of PhMNs and axons...
Diaphragm muscle (DIAm) motor units comprise a phrenic motor neuron (PhMN), the phrenic nerve and the muscle fibers innervated, with the size of PhMNs and axons characteristic of motor unit type. Smaller PhMNs and their axons comprise slow (type S) and fatigue-resistant (type FR) DIAm motor units, while larger PhMNs and their axons comprise more fatigable (type FF) motor units. With aging, we have shown a loss of larger PhMNs, consistent with selective atrophy of type IIx/IIb DIAm fibers and reduced maximum DIAm force. In the present study, we hypothesized that with aging there is a loss of larger myelinated phrenic α motor axons. Female and male young (6 months) and old (24 months) Fischer 344 rats were studied. PhMNs were retrogradely labeled by intrapleural injection of 488-conjugated CTB. The phrenic nerves were excised ~1 cm from the DIAm insertion and mounted in resin, and phrenic α motor axons were delineated based on size (i.e., >4 μm diameters). In older rats, the number of larger PhMNs and larger phrenic α motor axons were reduced. There were no differences in non-α axons. In addition, there was evidence of demyelination of larger phrenic α motor axons in older rats. Together, these findings are consistent with the selective age-related vulnerability of larger PhMNs and denervation of type FF motor units, which may underlie DIAm sarcopenia.
Topics: Rats; Male; Female; Animals; Aging; Motor Neurons; Rats, Inbred F344; Sarcopenia; Diaphragm; Axons; Fatigue
PubMed: 36695744
DOI: 10.14814/phy2.15587 -
Respiratory Medicine Case Reports 2019Bilateral phrenic nerve paralysis is a rare potentially life-threatening condition which is usually due to trauma (including surgery) or neurologic disease. We present a...
Bilateral phrenic nerve paralysis is a rare potentially life-threatening condition which is usually due to trauma (including surgery) or neurologic disease. We present a patient with apparent rapid onset bilateral phrenic nerve paralysis whose primary symptom was severe positional (supine) dyspnea with profound supine oxygen desaturation. Nerve conduction study abnormalities of the phrenic nerves and some left brachial plexus nerves suggested a diagnosis of ALS. He was treated with supportive night time ventilatory assistance (BiPAP) and over 4 years his condition recovered essentially completely. In retrospect the most likely diagnosis was a rare brachial plexopathy referred to as neuralgic amyotrophy.
PubMed: 31681533
DOI: 10.1016/j.rmcr.2019.100953 -
Journal of Neurophysiology Sep 2021Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by...
Plasticity is a hallmark of the respiratory neural control system. Phrenic long-term facilitation (pLTF) is one form of respiratory plasticity characterized by persistent increases in phrenic nerve activity following acute intermittent hypoxia (AIH). Although there is evidence that key steps in the cellular pathway giving rise to pLTF are localized within phrenic motor neurons (PMNs), the impact of AIH on the strength of breathing-related synaptic inputs to PMNs remains unclear. Furthermore, the functional impact of AIH is enhanced by repeated/daily exposure to AIH (dAIH). Here, we explored the effects of AIH versus 2 wk of dAIH preconditioning on spontaneous and evoked phrenic responses in anesthetized, paralyzed, and mechanically ventilated rats. Evoked phrenic potentials were elicited by respiratory cycle-triggered lateral funiculus stimulation at the C2 spinal level delivered before and 60 min post-AIH (or the equivalent in time controls). Charge-balanced biphasic pulses (100 μs/phase) of progressively increasing intensity (100-700 μA) were delivered during the inspiratory and expiratory phases of the respiratory cycle. Although robust pLTF (∼60% from baseline) was observed after a single exposure to moderate AIH (3 × 5 min; 5-min intervals), there was no effect on evoked phrenic responses, contrary to our initial hypothesis. However, in rats preconditioned with dAIH, baseline phrenic nerve activity and evoked responses were increased, suggesting that repeated exposure to AIH enhances functional synaptic strength when assessed using this technique. The impact of daily AIH preconditioning on synaptic inputs to PMNs raises interesting questions that require further exploration. Two weeks of daily acute intermittent hypoxia (dAIH) preconditioning enhanced stimulus-evoked phrenic responses to lateral funiculus stimulation (targeting respiratory bulbospinal projection to phrenic motor neurons). Furthermore, dAIH preconditioning enhanced baseline phrenic motor output responses to maximal chemoreflex activation in intact rats.
Topics: Animals; Evoked Potentials; Hypoxia; Male; Motor Neurons; Neuronal Plasticity; Phrenic Nerve; Rats; Rats, Sprague-Dawley
PubMed: 34260289
DOI: 10.1152/jn.00112.2021