Respiratory Stimulation for Cough Using a 12-Channel Neuroprosthetic Platform with Intramuscular Mapping and Permaloc® Electrodes: Acute Studies in Adult Canines

<p><em>Objective:</em><strong> </strong>Optimal methods of combined abdominal, upper-thoracic<em> </em>and diaphragm muscles stimulation for cough were studied using a 12-Channel Neuroprosthetic Platform and intramuscular Mapping and Permaloc^®electrodes<em>.</em></p><p><em>Methods: </em>Large respiratory volumes were induced in six, adult, respiratory-apneic canines. Optimal abdominal stimulation used three or four bilateral sets of Mapping electrodes just dorsal to the abdominal lateral line, upper-thoracic optimization included two or three sets of these electrodes implanted ventral to the axilla, and diaphragm stimulation used two bilateral sets of Permaloc^®implanted lateral to the central tendon. Combined muscle stimulation tests followed testing in individual muscles and included brief periods of tracheal tube clamping as a model of glottal closure to increase flow. For upper-thorax stimulation a safety factor was determined, to avoid the induction of heart arrhythmia, as the ratio of the highest total current with 12 sets of electrodes in the upper-thorax that did not induce arrhythmia, or the maximal current of 1,200 mA, to the optimized total current for a maximal inspiration.</p><p><em>Results:</em><strong> </strong>Maximal abdominal expiration was 257<span style="text-decoration: underline;">+</span>31 ml, upper-thorax inspiration was 409<span style="text-decoration: underline;">+</span>91 (n = 6) ml, and diaphragm stimulation was 377 ± 39 ml (n = 6). Combined muscles stimulation was additive; upper-thorax followed immediately by abdominal stimulation increased the volume to 673 ± 118 while further adding the diaphragm resulted in 914 ± 77 ml. Peak flow was significantly increased for combined extradiaphragmatic stimulation from 1,582 ± 205 ml/s by the glottal closure maneuver to1,217 ± 189 ml/s (n =6). Safety from heart arrhythmia for upper-thorax stimulation was 5 for one animal where arrhythmia occurred and great than 16.4 ± 0.9 for four other animals with no arrhythmia.</p>

Differential effects of respiratory and electrical stimulation-induced dilator muscle contraction on mechanical properties of the pharynx in the pig

Respiratory stimulation (RS) during sleep often fails to discontinue flow limitation, whereas electrical stimulation (ES) of the hypoglossus (HG) nerve frequently prevents obstruction. The present work compares the effects of RS and HG-ES on pharyngeal mechanics and the relative contribution of tongue muscles and thoracic forces to pharyngeal patency. We determined the pressure-area relationship of the collapsible segment of the pharynx in anesthetized pigs under the following three conditions: baseline (BL), RS induced by partial obstruction of the tracheostomy tube, and HG-ES. Parameters were obtained also after transection of the neck muscles and the trachea (NMT) and after additional bilateral HG transection (HGT). In addition, we measured the force produced by in situ isolated geniohyoid (GH) during RS and HG-ES. Intense RS was recognized by large negative intrathoracic pressures and triggered high phasic genioglossus and GH EMG activity. GH contraction produced during maximal RS less than a quarter of the force obtained during HG-ES. The major finding of the study was that RS and ES differed in the mechanism by which they stabilized the pharynx: RS lowered the pressure-area slope, i.e., reduced pharyngeal compliance (14.1 ± 2.9 to 9.2 ± 1.9 mm2/cmH2O, P < 0.01). HG-ES shifted the slope toward lower pressures, i.e., lowered the calculated extraluminal pressure (17.4 ± 5.8 to 9.2 ± 7.4 cmH2O, P < 0.01). Changes during RS and HG-ES were not affected by NMT, but the effect of RS decreased significantly after HGT. In conclusion, HG-ES and RS affect the pharyngeal site of collapse differently. Tongue muscle contraction contributes to pharyngeal stiffening during RS.

The role of central vasopressin receptors in the modulation of autonomic cardiovascular controls: a spectral analysis study

Although it has been suggested that vasopressin (VP) acts within the central nervous system to modulate autonomic cardiovascular controls, the mechanisms involved are not understood. Using nonpeptide, selective V1a, V1b, and V2 antagonists, in conscious rats, we assessed the roles of central VP receptors, under basal conditions, after the central application of exogenous VP, and after immobilization, on cardiovascular short-term variability. Equidistant sampling of blood pressure (BP) and heart rate (HR) at 20 Hz allowed direct spectral analysis in very-low frequency (VLF-BP), low-frequency (LF-BP), and high-frequency (HF-BP) blood pressure domains. The effect of VP antagonists and of exogenous VP on body temperature (Tb) was also investigated. Under basal conditions, V1a antagonist increased HF-BP and Tb, and this was prevented by metamizol. V1b antagonist enhanced HF-BP without affecting Tb, and V2 antagonist increased VLF-BP variability which could be prevented by quinapril. Immobilization increased BP, LF-BP, HF-BP, and HF-HR variability. V1a antagonist prevented BP and HR variability changes induced by immobilization and potentiated tachycardia. V1b antagonist prevented BP but not HR variability changes, whereas V2 antagonist had no effect. Exogenous VP increased systolic arterial pressure (SAP) and HF-SAP variability, and this was prevented by V1a and V1b but not V2 antagonist pretreatment. Our results suggest that, under basal conditions, VP, by stimulation of V1a, V1b, and cognate V2 receptors, buffers BP variability, mostly due to thermoregulation. Immobilization and exogenous VP, by stimulation of V1a or V1b, but not V2 receptors, increases BP variability, revealing cardiorespiratory adjustment to stress and respiratory stimulation, respectively.

Effect of positional changes of anatomic structures on upper airway dilating muscle shortening during electro- and chemostimulation

Positional changes of anatomic structures surrounding the upper airway are known to affect pharyngeal mechanics and collapsibility. We hypothesized that these alterations also affect the ability of the upper airway dilator muscles to enlarge the pharynx by altering their ability to shorten when activated. Using sonomicrometry, we evaluated in seven anesthetized dogs the effects of changes in tracheal and head position on the length of the genioglossus (GG) and the geniohyoid (GH) and the effects of these positional changes on the magnitude of shortening of the two muscles in response to electro- (ES) and chemostimulation (CS). Caudal traction of the trachea lengthened the GG and GH in all dogs, whereas cranial displacement of the trachea and flexion of the head to a vertical position shortened the muscles. Compared with the magnitude of ES-induced shortening in the neutral position, ES-induced shortening of the GG was 144.7 ± 14.6, 49.3 ± 4.3, and 33.5 ± 11.6% during caudal and cranial displacement of the trachea and during head flexion, respectively. Similar effects of the positional changes were found for the GH, as well as for both muscles during respiratory stimulation with Pco2 of 90 Torr at the end of CO2 rebreathing, although inspiratory muscle shortening during CS reached only one-quarter to one-third of the magnitude observed during ES. We conclude that positional alterations of anatomic structures in the neck have a dramatic effect on the magnitude of shortening of the activated GG and GH, which may reduce substantially their ability to protect pharyngeal patency.

Determinants of Fatal Apnea Responses to Acid Stimulation of the Larynx in Piglets

Objectives: This study explores the physiological determinants of laryngeal chemoreflex (LCR) response severity under hypoxic conditions. Methods: Thirty-four piglets underwent hypoxic laryngeal stimulation. Physiologic data were collected, and responses were graded as mild, moderate, or profound. Results: Prestimulation hypoxia caused respiratory depression and carbon dioxide retention in profound responders and respiratory stimulation in mild and moderate responders (p < .05). Resumption of respiration occurred in all animals when the Paco2 rose by a mean ± SD of 15.1 ± 6.5 mm Hg (p > .05). There was a significant difference between mild, moderate, and severe responders in change in arterial Pao2 and hydrogenated hemoglobin saturation during the LCR-induced response (p < .001 for both). Conclusions: Resumption of respiration is associated with accumulation of arterial Paco2. The respiratory response to hypoxia predicts the severity of the LCR response. The severity of the LCR-induced response is associated with changes in arterial Pao2 and hydrogenated hemoglobin saturation during the LCR-inducedapnea.

Glycine at hypoglossal motor nucleus: genioglossus activity, CO2 responses, and the additive effects of GABA

There is evidence for glycine and GABAA-receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo, and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. This study tests the hypotheses that glycine at the hypoglossal motor nucleus (HMN) will suppress genioglossus (GG) muscle activity, even in the presence of hypercapnic respiratory stimulation, and the effects of glycine will be blocked by strychnine. We also determined whether coapplication of glycine and muscimol (GABAA- receptor agonist) to the HMN is additive in suppressing GG activity. Twenty-four urethane-anesthetized, tracheotomized, and vagotomized rats were studied. Diaphragm and GG activities, the electroencephalogram, and blood pressure were recorded. Microdialysis probes were implanted into the HMN for delivery of artificial cerebrospinal fluid (control), glycine (0.0001–10 mM), or muscimol (0.1 μM). Increasing glycine at the HMN produced graded suppression of GG activity ( P < 0.001), although the GG still responded to stimulation with 7% inspired CO2( P = 0.002). Strychnine (0.1 mM) reversed the glycine-mediated suppression of GG activity, whereas combined glycine and muscimol were additive in GG muscle suppression. It remains to be determined whether the recruitment of such glycine and GABA mechanisms explains the periods of major GG suppression in behaviors such as rapid eye movement sleep.