Voluntary Respiration Research Articles

Ventral and dorsal cervical spinal cord electrical epidural stimulation facilitated respiration differently in the presence of opioids in human via different neural circuits

Opioid overdose is one of the leading causes of overdose related deaths in the United States of America, accounting for 70.6% of overdose fatalities in 2019 alone. A leading cause of death among opioid overdoses is respiratory depression. Epidural electrical stimulation (EES) emerges as a novel approach of facilitating rhythmic motor activities such as locomotion and respiration. Previous studies conducted in humans and rodent models demonstrated respiratory augmentations induced by EES delivered to the dorsal cervical spinal cord. Importantly, EES at the dorsal cervical spinal cord opposes opioid-induced respiratory depression in human. To reveal the mechanism underpins how cervical EES modulate the respiratory neural circuit, we conducted this comparative study between dorsal cervical EES to the ventral EES in patients with opioid-induced respiratory suppression or depression. We hypothesize that the ventral cervical EES activates the local motor neuronal pools while the dorsal EES recruits both sensory and motor cervical circuits as well as accesses supraspinal structures such as medulla. We recruited and consented 25 patients who underwent anterior (ventral) cervical spinal cord surgery and compared the effect of ventral cervical EES to to the effect of dorsal cervical ESS in a dataset that we collected from 18 patients undergoing cervical spinal surgery. In the 25 patients, the EES was deliver to the ventral surface of spinal cord ranging from cervical level 3 to 7 (C3 to C7) for no more than 90 seconds at the optimal intensity ranging from 0.5 mA to 5 mA with stimulation frequencies 5 Hz or 30 Hz. In both the dorsal and ventral EES groups, the subjects were anesthetized with low dose or high dose remifentanil that partially or completely depressed voluntary respiration. We observed three main differences between the dorsal and ventral cervical EEST in regulating respiration in the presence of remifentanil. First, dorsal cervical EES induced the resetting of inspiratory rhythm while ventral cervical EES did not. Second, dorsal but not ventral cervical EES induced longer lasting respiratory modulation after the stimulation stopped. Third, dorsal cervical EES induced both frequency and amplitude changes of respiration while ventral cervical EES modulated the amplitude of the respiration more significantly. These observations suggest that the dorsal and ventral cervical EES facilitate respiration via different neural circuits. This work was supported by the National Institute of Drug Abuse in the National Institutes of Health: R01 DA047637, Louis and Harold Price Foundation, H & H Evergreen Foundation, and J. Yang Family Foundation. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Voluntary Respiration Control: Signature Analysis by EEG.

The perception of voluntary respiratory consciousness is quite important in some situations, such as respiratory assistance and respiratory rehabilitation training, and the key signatures about voluntary respiration control may lie in the neural signals from brain manifested as electroencephalography (EEG). The present work aims to explore whether there exists correlation between voluntary respiration and scalp EEG. Evoke voluntary respiration of different intensities, while collecting EEG and respiration signal synchronously. Data from 11 participants were analyzed. Spectrum characteristics at low-frequency band were studied. Computation of EEG-respiration phase lock value (PLV) and EEG sample entropy were conducted as well. When breathing voluntarily, the 0-2 Hz band EEG power is significantly enhanced in frontal and right-parietal area. The distance between main peaks belonging to the two signals in 0-2 Hz spectrum graph tends to get smaller, while EEG-respiration PLV increases in frontal area. Besides, the sample entropy of EEG shows a trend of decreasing during voluntary respiration in both areas. There's a strong correlation between voluntary respiration and scalp EEG. Significance: The discoveries will provide guidelines for developing a voluntary respiratory consciousness identifying method and make it possible to monitor people's intention of respiration by noninvasive BCI.

Changing medical care for amyotrophic lateral sclerosis patients and cause of death - review of muscular dystrophy wards (1999-2013)

We analyzed the records of inpatients with amyotrophic lateral sclerosis (ALS) treated at 27 specialized institutions for muscular dystrophy in Japan from 1999 to 2013 registered in a database on October 1 of each year. The total number of ALS inpatients in 1999 was 29, then that showed rapid increases in 2006 and 2007, and reached 164 in 2013. Age regardless of year was predominantly greater than 50 years. In 1999, the respirator dependent rate was 68.9% and then increased to 92.7% in 2013, while the oral nutritional supply rate was 41.4% in 1999 and decreased to 10.4% in 2013. The number of deaths from 2000 to 2013 was 118. Cause of death was respiratory failure in 26 of 30 patients who maintained voluntary respiration at the time of death and in 5 of 6 with non-invasive ventilation. On the other hand, the main cause of death in patients with tracheostomy invasive ventilation was respiratory infection, which was noted in 26 of 82, while other causes varied. It is expected that the number of ALS patients admitted to specialized institutions with muscular dystrophy wards will continue to increase.

The phase-lock effect of voluntary respiration on detection of fearful faces

The phase-lock effect of voluntary respiration on detection of fearful faces

Ondine's curse: myth meets reality

Ondine's curse is one of the most enchanting mythical tales in the field of Medicine. The nymph Ondine was an immortal water spirit who became human after falling in love for a man, marrying him, and having a baby. In one of the versions of the tale, when she caught her husband sleeping with another woman, she cursed him to remain awake in order to control his own breathing. During the 19th century, the rare syndrome characterized by loss of autonomic breath control, while voluntary respiration remains intact, was cleverly named “Ondine's curse”. Nowadays, the term Ondine's curse is usually associated with congenital central hypoventilation syndrome; however, in medical literature, it also designates several respiratory disorders. Here, we present a review of the myth focused on history, arts and medicine.

A Novel Apprehension of the Primary Lung Meridian, Sinew Channel, Divergent Channel, Luo-Connecting Channel Acting as a Single Unit System to Serve Respiration Function Based on Modern Neurophysiology and Kinesiology

The TCM philosophy of a meridian and associated channels pertains to the specific function of one or more organs. We define the Lung Primary Meridian (LUM) together with the Lung Sinew (LUSC), Divergent (LUDC), Luo-connecting (LULCC) Channels as a system of routes plus some parts of the body (such as muscles) to fulfil respiration, as a main function under different situations. There is very limited information about the Lung associated channels in classical literature of TCM. With a clear focus on the function of respiration, we have carried out a detailed analysis of the biomedical consequence of stimulating the LUM, analysed the roles played by LUSC, LUDC, and LULCC. The updated LUM and LUDC include acupoints of other meridians, serving the same purpose of performing satisfactory respiration starting from checking the quality of the inflow through the nose. The LUSC includes the respiratory muscles (plus the associated connective tissues) extending to various parts of the body. The muscles of the limb (as part of the LUSC) embrace the nerves that provide routes for somatosensory reflexes and play the role of locomotion, providing voluntary respiration via the pectoralis muscles. The muscles of LUSC are bounded by stiff connective tissue layers, forming compartments, and are part of the pulley system for various body locomotions. Within a compartment, the interstitial fluid, blood, lymph flows must be potent to protect the associated nerves related to LUM; the healthy state of the LUSC also provides freedom of various types of locomotion. The LULCC exists because the vagus nerve has a part of it passing through the spinal cords all the way down to the sacrum domain, with exiting nerve innervating two-third of the large intestine. The crucial steps of our deductions are supported by experimental evidence based on modern neurophysiology and kinesiology. We discover that all the four channels stated above work as a unit system to allow respiration to be possible under various postures/conditions. The complexity of structures and processes is eased off by providing 29 figures and 13 tables for the relevant muscles and nerves. In addition to respiration, the Lung system in TCM context includes interaction of this system with the sweat gland and neuroendocrine system; such aspects will be left to another study.

Psychological Mediation of Dysfunction and Hyperfunction of Respiratory Regulation.

This research investigates the continuum between the dysfunction and the hyperfunction of breath regulation and presents the psychological mediation that supports or disrupts this regulation. The pilot study compared breathing regulation in patients with hyperventilation syndrome (HVS), free divers, and healthy volunteers. To examine the ability of voluntary respiration regulation, breath holding involving “easy-going” and “struggling” phases was used. Psychological mediation was assessed through (a) respiratory experience interviews, (b) anxiety levels, and (c) psycho-semantic techniques. Free divers have a bigger “positive breathing vocabulary” and can endure the conflict between the physiological need to inhale and the voluntary motivation to hold their breath for longer. The connection between emotions and negative breathing experience in patients with HVS leads to less breathing control.

Automatic and voluntary respiration failure induced by unilateral lateral-medurally infarction

Automatic and voluntary respiration failure induced by unilateral lateral-medurally infarction

Effects of voluntary respiration control on reaction time and subjective sleepiness

Effects of voluntary respiration control on reaction time and subjective sleepiness

Pearls & Oy-sters

Ondine's curse is an eponym that refers to central alveolar apnea/hypopnea observed among patients with acquired or congenital brainstem disorders. This condition results in loss of automatic and/or voluntary respiration with characteristic polysomnographic finding of impaired ventilator responses to hypercapnia and sleep apnea, which are more pronounced during non-REM sleep, less in REM sleep, and least during wakefulness.

Ascending tonic‐clonic seizure syndrome in a dog following inadvertent intrathecal use of ionic contrast agent

To describe the successful management of ascending tonic-clonic seizure syndrome in a dog after inadvertent intrathecal administration of ionic contrast material. A 7-year-old, 5.9 kg, male castrated Miniature Pinscher inadvertently received intrathecal ionic contrast material during a myelogram to investigate cervical pain. Ascending tonic-clonic muscle spasms quickly progressed to generalized seizure activity that was resistant to anticonvulsant medications. The dog developed complete respiratory arrest, which necessitated mechanical ventilatory support for 26 hours. Pneumonia developed and was treated successfully. After resolution of seizure activity and resumption of voluntary respiration, the dog remained tetraparetic for 16 days and was not able to walk on his own for 20 days post contrast injection. Despite a prolonged recovery, the patient survived and recovered normal neurologic function. Intrathecal administration of ionic contrast material resulting in ascending tonic-clonic seizure syndrome is rarely reported in the human and veterinary literature. No previous veterinary report has described successful treatment after prolonged respiratory arrest. In previous veterinary reports, patients recovered complete neurologic function within hours to days in contrast to this report in which the patient was tetraparetic for 16 days. This report demonstrates complete recovery from intrathecal ionic contrast administration is possible despite a high dose of contrast and a prolonged recovery.

Reliability of the Deep Abdominal Muscle Thickness Measurements Using Ultrasonography in Normal Subjects

[Purpose] This study was performed to investigate the changes of thickness and reliability of the measurements of lateral abdominal muscles during respiratory maneuvers using ultrasonography. [Subjects and Methods] Participants were 10 healthy male volunteers (26.4±2.7 years old). Ultrasound B-mode scanning was performed with the subjects lying supine and the probe was placed transversely midway between the costal inferior border and the crista iliaca. The muscle thickness of the external oblique (EO), internal oblique (IO), and transverses abdominal (TA) were measured under two conditions: resting expiration (Rex) and maximum expiratory effort (MEE). Percent thickness change was calculated as thickness MME — thickness Rex / thickness Rex×100%. Interclass correlation coefficients (ICC 1, 2) were used to estimate reliability. [Results] Muscle thickness during MME were significantly increased compared with that during Rex and the EO thickness was significantly decreased. Intraexaminer reliability estimates ranged from 0.97 to 0.82 for EO, 0.94 to 0.81 for IO and 0.67 to 0.86 for TA. [Conclusions] We conclude that the thickness of the lateral abdominal muscles is influenced by voluntary respiration, and the assessment of the thickness by means of ultrasonography is adequately reliable. This information may be useful for deciding exercise prescription.

Neuroanatomical correlates of olfactory performance

We investigated associations between olfactory function and gray matter thickness in 46 healthy young subjects by means of an automated technique for measuring cortical thickness. We used an extended version of the Sniffin' Sticks test to assess olfactory function, including odor threshold, concentration discrimination, quality discrimination, and odor identification. We observed a correlation between olfactory performance and cortical thickness of structures involved in earlier and later stages of chemosensory processing such as right medial orbitofrontal cortex, right insula, and adjacent cortex. Furthermore, we found significant bilateral correlations of olfactory performance with cortical thickness of areas around the central sulcus bilaterally, structures responsible for voluntary respiration and sniffing. In addition to expected general sex effects on cortical thickness, we observed areas, such as the entorhinal cortex, occipital cortex, intraparietal sulcus and insula (all in the right hemisphere), where the correlation between higher order olfactory functions and cortical thickness differed between women and men. These data demonstrate, for some neuroanatomical structures, a link between cortical thickness and olfactory function, in that thicker cortex is usually associated with better performance, but not always. This association between anatomy and olfactory performance suggests a possible biological explanation for the high degree of individual differences and sex effects observed in higher order olfactory tasks.

Acute Evaluation of Transthoracic Impedance Vectors Using ICD Leads

Minute ventilation (MV) has been proven to be very useful in rate responsive pacing. The aim of this study was to evaluate the feasibility of using implantable cardioverter-defibrillator (ICD) leads as part of the MV detection system. At implant in 10 patients, the transthoracic impedance was measured from tripolar ICD, tetrapolar ICD, and atrial lead vectors during normal, deep, and shallow voluntary respiration. MV and respiration rate (RespR) were simultaneously measured through a facemask with a pneumotachometer (Korr), and the correlations with impedance-based measurements were calculated. Air sensitivity was the change in impedance per change in respiratory tidal volume, ohms (Omega)/liter (L), and the signal-to-noise ratio (SNR) was the ratio of the respiratory and cardiac contraction components. The air sensitivity and SNR in tripolar ICD vector were 2.70 +/- 2.73 ohm/L and 2.19 +/- 1.31, respectively, and were not different from tetrapolar. The difference in RespR between tripolar ICD and Korr was 0.2 +/- 1.91 breaths/minute. The regressed correlation coefficient between impedance MV and Korr MV was 0.86 +/- 0.07 in tripolar ICD. The air sensitivity and SNR in tripolar and tetrapolar ICD lead vectors did not differ significantly and were in the range of the values in pacemaker leads currently used as MV sensors. The good correlations between impedance-based and Korr-based RespR and MV measurements imply that ICD leads may be used in MV sensor systems.

Transesophageal mediastinoscopy by submucosal endoscopy with mucosal flap safety valve technique

Indications for NOTES (natural orifice transluminal endoscopic surgery) studied so far are limited to intra-abdominal surgery. To determine the technical feasibility and the safety of transesophageal mediastinocosopy by using the submucosal endoscopy with mucosal flap safety valve (SEMF) technique. Two-week survival study with 4 porcine models. High-pressure carbon dioxide injection and balloon dissection created a large submucosal working space for insertion of a cap-fitted endoscope. The muscularis propria was resected inside the submucosal space, and the mediastinoscopy was performed by using the endoscope inserted via the myotomy site. The muscular defect was sealed with the overlying mucosal flap, and the mucosal entry site was closed with clips. Repeated endoscopy and necropsy were performed 2 weeks after the procedure. With the SEMF technique, the posterior mediastinum was successfully accessed in all animals. Three pigs survived 2 weeks without clinical complications, and the defects were completely sealed by the mucosal flap. One pig with proximal esophageal mediastinal entry managed under voluntary respiration was euthanized because of pleural injury. The SEMF technique provided safe entry into the mediastinum, with a protective submucosal tunnel that prevented mediastinal soiling. Mid to distal esophageal access is safer than the higher level access. Mechanical ventilation might allow safer respiratory support.

Automatic respiration in amyotrophic lateral sclerosis

Sirs: Several patients with pathologically proven amyotrophic lateral sclerosis (ALS) have been reported to run a benign course without need for a mechanical ventilator [5, 6, 9]. We observed autonomous breathing in a case of long-surviving ALS, and the effects of the metabolic control system on respiration were revealed. The patient in this report is a housewife with no family history of neuromuscular disease or consanguineous pedigree. She noticed difficulty in speech at age 53 years, followed by gradual muscular weakness in her upper and lower extremities. She was diagnosed as ALS based on the clinical and EMG findings. At age 56, her developing dyspnea led to a tracheostomy and mechanical ventilation control. Three months later, she was transferred to our hospital. At that time, she was alert and had no sensory deficits. Though her ocular movements were normal, there was both moderate weakness of her facial muscles together with marked tongue atrophy with fasciculation. Muscular atrophy and motor weakness were remarkable in the upper limbs and moderate in the lower limbs. Muscle stretch reflex was hyperactive in facial muscles, jaw jerk and lower extremities, but there was areflexia in the upper extremities. There was foot clonus but no Babinski’s reflex. In spite of being under mechanical ventilation when admitted to our hospital, spontaneous breathing with SpO2 of 97–98 % has been observed during these past three years since admission. Now, she is 60 years old and in a state of tetraplegia with marked facial muscle weakness. PTR and ATR are still hyperactive. She is alert, very intelligent, and communication is maintained via a computer-assisted communication system. Neuroimaging studies show normal finding. Her respiration states are minute volume of 3–4 l and PO2 92.7 Torr/PCO2 43.5 Torr without mechanical ventilator, but she cannot voluntarily control her breathing (Fig. 1A). Her attempt to hold her breath causes decreasing amplitude of her breathing while maintainig respiration rhythm, and her intention to hold her breathing merely increases the amplitude. Laughing causes irregular respiration rhythm and increases amplitude (Fig. 1B), and her cough reflex from tracheal stimulation is positive (Fig. 1C). She cannot speak via a tracheostomy tube equipped with a speech bulb. The hypercapnic response was measured by a modification of Read’s method [10], which was performed after obtaining the informed consent of the patient and her family. She rebreathed 5 % CO2 in oxygen from a 7 l anesthesia bag. The results revealed an augmentation of ventilation in response to the progressive increase of PtCO2 up to 55 Torr (Fig. 2). Breathing is controlled separately by the autonomic and voluntary pathways [1]. A discrete lesion in the central nervous system may cause a selective paralysis of one type of respiration, but spare the other. The respiratory findings in the present case are a loss of voluntary respiration but preservation of autonomous rhythm, metabolic control and evidence of activation in response to emotional stimuli. These findings have been reported in patients with lesions in the ventral pons [2, 3, 4, 8] and bilateral pyramidal tracts [7]. The reverse condition of an impaired autonomic but preserved volitional system is called central alveolar hypoventilation syndrome or Ondine’s curse [11, 12], which requires mechanical ventilation during sleep. Preservation of autonomous respiration suggests intact medullary respiratory neurons such as the ambiguous and retroambiguous nuclei of the vagus, and respiratory rhythm-generating neurons in the caudal ventral pons [1]. Also, this patient showed normal activity of CO2/H+ sensitive neurons which are located in the solitary nuclei and ventrolateral field of the caudal medulla oblongata [1]. The influence of emotional laughing on the autonomic respiration rhythm suggests the retained pathway of limbic cortex to these respiratory neurons [3, 8]. Descending bulbospinal respiratory pathways, which run in the anterior funiculus [1], and the anterior horn cell originating the phrenic nerve must be preserved to some degree to maintain spontaneous breathing. At the same time, a loss of volitional respiration indicates quite severe degeneration in the corticospinal tract, which is indicated by hyperactive tendon reflex in extremely weakened muscle. This case shows a peculiar symptom of impaired volitional but preserved autonomous respiration. To our knowledge, this is the first report of physiological study in ALS with a benign respiration course. Metabolic stimulation seems to be useful to reinforce the respiratory movement in such patients. LETTER TO THE EDITORS

椎骨動脈りゅうに対する直達術・血管内手術における術後中枢性呼吸機能不全についての検討

Vertebral aneurysm surgery and endovascular procedures carry a potential risk of postoperative respiratory disorders. This is because the respiratory centers, which are located in the reticular formation of the ponto-medullary junction, are supplied by perforators originating from the basilar artery (BA), the vertebral artery (VA) close to the VA union, the proximal posterior inferior cerebellar artery (PICA), and the proximal anterior inferior cerebellar artery (AICA). A retrospective study of 13 patients (7 men and 6 women, mean age 54.5 years, range 21-72 years) surgically treated for vertebral aneurysms during the past 4 years in our hospital was done to determine the relationship between treatment modality and postoperative central respiratory dysfunction. Among our patients, there were 4 saccular aneurysms, 8 dissecting aneurysms and 1 giant fusiform aneurysm; 8 aneurysms were located in the VA between the origin of the PICA and the VA union (including 2 cases whose PICAs were not confirmed by angiography); 4 aneurysms were in the VA-PICA junction; and 1 aneurysm was located in the PICA. Six aneurysms were treated by direct surgery: neck clipping was performed in 3 cases; proximal clipping of the VA at the site distal to the PICA was done in 1 case; trapping was done in 1 case; and trapping with an occipital artery-PICA anastomosis was done in 1 case. Seven aneurysms were treated by endovascular procedure with intra-aneurysmal coil embolization. Respiratory arrest occurred in 3 cases whose postoperative course was uneventful. Rerupture and medullary infarction were not confirmed by CT/MRI obtained immediately and a few days after the respiratory arrests. However, more than half of the intra-dural VA was occluded proximally from the VA union after the direct surgical/endovascular procedure, which included proximal clipping for a giant fusiform aneurysm in 1 case and coil embolization for dissecting aneurysms in 2 cases. The periods between surgery and respiratory arrest were 10 hours, 4 days, and 32 days, respectively, for the 3 patients. Voluntary respiration eventually resumed in 2 patients. In the surgical treatment of vertebral aneurysms, the possibility of respiratory complications should be kept in mind even though the early postoperative course may be uneventful. Postoperative respiratory failure can be reversed. Thus prompt diagnosis and treatment under close observation are mandatory, especially in cases with a high risk for postoperative central respiratory dysfunction.

小児でセボフルラン麻酔を行う時手術中は自発呼吸のみで維持可能か？

小児でセボフルラン麻酔を行う時手術中は自発呼吸のみで維持可能か？

Enhancement of parasympathetic cardiac activity during activation of muscle metaboreflex in humans.

We measured the changes in heart rate (HR) variability estimated from the standard deviation of the R-R intervals to evaluate cardiac parasympathetic tone noninvasively before and during activation of muscle metaboreflex induced by postexercise muscle ischemia. Eight healthy male subjects performed sustained handgrip at 50% maximal voluntary contraction followed by forearm occlusion. Mean arterial pressure, cardiac stroke volume, and ratio of cardiac preejection period to left ventricular ejection time (PEP/LVET) were also measured. During the 2-min occlusion after 60 s of handgrip with voluntary respiration, HR variability and mean arterial pressure were significantly increased from baseline (54.4 +/- 6.1 to 80.1 +/- 12.8 ms and 81 +/- 1 to 99 +/- 3 mmHg, respectively) and PEP/LVET was decreased from resting level of 0.404 +/- 0.022 to 0.363 +/- 0.036. During occlusion and recovery, HR did not change from baseline level in any experiment. There was no influence of occlusion itself or of cessation of exercise per se on any parameters. Although overall enhanced HR variability was seen, probably due to lower breathing frequency and larger tidal volume, similar results were also obtained from an experiment with controlled respiration, showing that the increase in HR variability was not due to the changes in tidal volume or breathing frequency during occlusion. In conclusion, the HR variability is increased during activation of the muscle metaboreflex induced by postexercise muscle ischemia in humans. This finding shows that the parasympathetic cardiac tone is enhanced during activation of the muscle metaboreflex in humans and balances enhanced cardiac sympathetic activity to result in an unchanged HR.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective Paralysis of Voluntary but Not Limbically Influenced Automatic Respiration

We describe a patient in whom a discrete infarction of the ventral basis pontis caused a complete loss of voluntary respiration, while automatic respiration remained intact. Respiratory excursions, quantified title volumes, and ventilatory response to carbon dioxide were normal, but the patient could not volitionally modify any respiratory parameters. Emotional stimuli producing laughter, crying, or anxiety appropriately modulated automatic respiration. This case established that pathways subserving limbic modulation of automatic respiration descend in the pontine tegmentum and/or lateral portion of the basis pontis spared by this lesion. Furthermore, descending limbic influences on automatic respiration are anatomically and functionally independent of the voluntary respiratory system.