Negative Pressure Stimuli Research Articles

Drive versus Pressure Contributions to Genioglossus Activity in Obstructive Sleep Apnea.

Rationale: Loss of pharyngeal dilator muscle activity is a key determinant of respiratory events in obstructive sleep apnea (OSA). After the withdrawal of wakefulness stimuli to the genioglossus at sleep onset, mechanoreceptor negative pressure and chemoreceptor ventilatory drive feedback govern genioglossus activation during sleep, but the relative contributions of drive and pressure stimuli to genioglossus activity across progressive obstructive events remain unclear. We recently showed that drive typically falls during events, whereas negative pressures increase, providing a means to assess their individual contributions to the time course of genioglossus activity. Objectives: For the first time, we critically test whether the loss of drive could explain the loss of genioglossus activity observed within events in OSA. Methods: We examined the time course of genioglossus activity (EMGgg; intramuscular electromyography), ventilatory drive (intraesophageal diaphragm electromyography), and esophageal pressure during spontaneous respiratory events (using the ensemble-average method) in 42 patients with OSA (apnea-hypopnea index 5-91 events/h). Results: Multivariable regression demonstrated that the falling-then-rising time course of EMGgg may be well explained by falling-then-rising drive and rising negative pressure stimuli (model R = 0.91 [0.88-0.98] [95% confidence interval]). Overall, EMGgg was 2.9-fold (0.47-∞) more closely associated with drive than pressure stimuli (ratio of standardized coefficients, βdrive:βpressure; ∞ denotes absent pressure contribution). However, individual patient results were heterogeneous: approximately one-half (n = 22 of 42) exhibited drive-dominant responses (i.e., βdrive:βpressure > 2:1), and one-quarter (n = 11 of 42) exhibited pressure-dominant EMGgg responses (i.e., βdrive:βpressure < 1:2). Patients exhibiting more drive-dominant EMGgg responses experienced greater event-related EMGgg declines (12.9 [4.8-21.0] %baseline/standard deviation of βdrive:βpressure; P = 0.004, adjusted analysis). Conclusions: Loss of genioglossus activity precipitating events in patients with OSA is strongly associated with a contemporaneous loss of drive and is greatest in those whose activity tracks drive rather than pressure stimuli. These findings were upheld for events without prior arousal. Responding to falling drive rather than rising negative pressure during events may be deleterious; future therapeutic strategies whose aim is to sustain genioglossus activity by preferentially enhancing responses to rising pressure rather than falling drive are of interest.

Sensory detection of threshold intensity resistive loads in severe obstructive sleep apnoea

Respiratory related evoked potentials (RREPs) were used to investigate whether sensory detection of small mid-inspiratory resistive loads (≈1.2–6.2 cmH2OL−1s), delivered during wakefulness, was impaired in obstructive sleep apnoea (OSA). It was reasoned that impaired detection of minor airway patency challenge may lead to difficult-to-remedy further collapse. There was a significant reduction in OSA (n=16) vs. control (n=17) participants in the slope of the relationship between the P1 RREP component amplitude, which reflects arrival of somatosensory information at the cortex, and stimulus intensity, expressed as change in epiglottic pressure (mean [95% confidence intervals]: −0.50 [−0.97, −0.03] vs. −1.78 [−2.54, −1.02]; P=0.004), suggesting a reduction in sensitivity to small respiratory loads. However there was no significant difference in sensitivity after background Pepi was taken into account (P=0.268). Additionally, there were no significant group differences in the threshold of the P1 amplitude/stimulus intensity relationship, or in the P1 latency. These results indicate a reduced sensitivity to detection of small upper airway negative pressure stimuli in OSA related to a reduction in mechanoreceptor activation (likely related to increased airway resistance in OSA vs. controls; P=0.002) rather than defective mechanosensory function.

Sensory Transduction in Human Teeth with Inflamed Pulps

The effects of pulpal inflammation on the sensitivity of dentin to cold (5°C) and negative hydrostatic pressure (−300 mm Hg) stimuli in man were compared, since recent evidence suggests that these stimuli excite different classes of sensory receptors. Dentin was exposed in premolars in 14 participants aged 15-25 years. Stimuli were applied to etched dentin immediately after cavity preparation and after the cavity had been filled with gutta percha for 7 days. This treatment increased significantly the intensity of pain produced by cold, and at the same time decreased that evoked by negative pressure stimuli. Pulpal blood flow was increased in the treated teeth, indicating that their pulps were inflamed. It is concluded that the sensory receptors responsible for the response to cold were probably sensitive to some change other than an outward flow of fluid in dentinal tubules, which would be caused by both forms of stimulus.

Electrophysiological observations on the effects of potassium ions on the response of intradental nerves to dentinal tubular flow in the cat

Objective To determine the effects of K + on the sensitivity of sensory receptors in teeth to fluid flow through dentine. Methods Evoked discharges were recorded from intradental nerves in anaesthetised cats during the application of 5 s hydrostatic pressure stimuli to exposed dentine through either normal Ringer's or Ringer's containing up to 255 mmol/l K +. The stimuli ranged between −500 and +500 mm Hg. Results The number of impulses evoked by a positive pressure stimulus increased, and the latency of the response decreased, as either the pressure or the K + concentration of the Ringer's was increased. The response to a negative pressure stimulus applied 2 s after a positive pressure pulse of equal but opposite amplitude decreased as either the intensity of the stimulus or the K + concentration of the Ringer's was increased. Conclusions Potassium ions that were transported into the dentine and pulp by bulk flow during the application of positive pressure stimuli increased the sensitivity of the receptors to inward tubular flow but decreased their sensitivity to outward flow.

A secondary reflex suppression phase is present in genioglossus but not tensor palatini in response to negative upper airway pressure.

On the basis of recent reports, the genioglossus (GG) negative-pressure reflex consists initially of excitation followed by a secondary state-dependent suppression phase. The mechanistic origin and functional role of GG suppression is unknown but has been hypothesized to arise from transient inhibition of respiratory active neurons as a protective reflex to prevent aspiration, as observed in other respiratory muscles (e.g., diaphragm) during airway occlusion. Unlike GG, tensor palatini (TP) is a tonic muscle with minimal respiratory phasic activation during relaxed breathing, although both muscles are important in preserving pharyngeal patency. This study aimed to compare GG vs. TP reflex responses to the same negative-pressure stimulus. We hypothesized that reflex suppression would be present in GG, but not TP. Intramuscular GG and TP EMGs were recorded in 12 awake, healthy subjects (6 female). Reflex responses were generated via 250-ms pulses of negative upper airway pressure (approximately -16 cmH2O mask pressure) delivered in early inspiration. GG and TP demonstrated reflex activation in response to negative pressure (peak latency 31+/-4 vs. 31+/-6 ms and peak amplitude 318+/-55 vs. 314+/-26% baseline, respectively). A secondary suppression phase was present in 8 of 12 subjects for GG (nadir latency 54+/-7 ms, nadir amplitude 64+/-6% baseline), but not in any subject for TP. These data provide further support for the presence of excitatory and inhibitory components of GG (phasic muscle) in response to brief upper airway negative-pressure pulses. Conversely, no reflex suppression below baseline was present in TP (tonic muscle) in response to the same stimuli. These differential responses support the hypothesis that GG reflex suppression may be mediated via inhibition of respiratory-related premotor input.

Venous blood redistribution alters the accuracy of Omron HEM-705CP.

Validation procedures of automated blood pressure measuring devices are carried out at rest only. We aimed to determine whether venous blood redistribution affects the accuracy of the OMRON HEM-705CP (Osc). Lower body negative pressure stimulus (-40 mmHg) (LBNP) was used to simulate changes of body position. Fifty-four young healthy volunteers had their blood pressure (BP) measured simultaneously by Osc and mercury sphygmomanometer (HgS) at rest (at 3 and 5 min) and during LBNP (at 7 and 9 min). Differences (delta) between HgS and Osc for systolic and diastolic BP (SBP and DBP) were calculated. The deltaSBP obtained in minute 9 (deltaSBP-9) was bigger than the one taken in minute 5(deltaSBP-5) (-2.89+/- 4.3 versus -1.35+/-5.2 mmHg, P<0.02). The rest of the deltaSBP values and all the deltaDBP values were constant at rest and during venous blood redistribution caused by LBNP. We calculated the fall in SBP separately for HgS and Osc by subtracting SBP-9 from SBP-5 for each patient. The fall measured by Osc was bigger than by HgS (-5.87+/-4.0 versus -4.3+/-4.5 mmHg; P<0.02). When graded according to British Hypertension Society protocol, Osc remained in the class of recommendation (A or B) for every minute of the procedure. Even if an oscillometric device passes various validation tests, they do not give sufficient information about its accuracy during venous blood redistribution. This knowledge is of particular importance when BP regulation abnormalities occurring during changes in body position are diagnosed with the oscillometric method.

Voltage-Induced Activation of Mechanosensitive Cation Channels of Leech Neurons

The voltage dependence of stretch-activated cation channels in leech central neurons was studied in cell-free configurations of the patch-clamp technique. We established that stretch-activated channels excised from identified cell bodies of desheathed ganglia, as well as from neurons in culture, were slowly and reversibly activated by depolarizing membrane potentials. Negative pressure stimuli, applied to the patch pipette during a slow periodical modulation of membrane potential, enhanced channel activity, whereas positive pressures depressed it. Voltage-induced channel activation was observed, with soft glass pipettes, both in inside-out and outside-out membrane patches, at negative and positive reference potentials, respectively. The results presented in this study demonstrate that membrane depolarization induces slow activation of stretch-activated channels of leech central neurons. This phenomenon is similar to that found in Xenopus oocytes, however, some peculiar features of the voltage dependence in leech stretch-activated channels indicate that specific membrane-glass interactions might not necessarily be involved. Moreover, following depolarization, stretch-activated channels in membrane patches from neurons in culture exhibited significantly shorter delay to activation (sec) than their counterparts from neurons of freshly isolated ganglia (hundreds of sec).

Central and reflex neural control of genioglossus in subjects who underwent laryngectomy

Inspiratory activation of the genioglossus (GG) may occur by central drive or as a reflex to negative airway pressure. To distinguish between these, we studied seven laryngectomy patients who breathe via tracheal stomas. Negative pressure stimuli (-15 and -25 cmH2O for 500 ms) were applied 1) at functional residual capacity and 2) during early inspiration via (i) the upper airway (UA) and (ii) the tracheal stoma. Intraoral surface GG electromyogram was quantified, as described previously (R. L. Horner, J. A. Innes, K. Murphy, and A. Guz, J. Physiol. Lond. 436: 15-29, 1991). Phasic GG activity was also measured from an integrated electromyogram during spontaneous and inspiratory loaded breathing. Reflex GG activation occurred with negative UA pressure both at functional residual capacity and during inspiration (P < 0.001), but pressure stimuli at the stoma caused no significant activation (P = 0.07). Phasic inspiratory activation occurred in four patients at rest and in all seven patients during inspiratory loading (P < 0.02). These patients demonstrate 1) reflex activation of the GG by negative UA pressure without airflow or respiratory effort and 2) central inspiratory GG activation that is not mediated by negative airway pressure.

Reflex vasopressin and renin modulation by cardiac receptors in humans.

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory function of hyoid muscles and hyoid arch.

The position of the hyoid arch suggests that it supports soft tissue surrounding the upper airway (UA) and can act to maintain UA patency. We also suspected that muscles inserting on the hyoid arch might show respiratory patterns of activity that could be affected by respiratory stimuli. To test these possibilities, we moved the hyoid arch ventrally in six anesthetized dogs either by traction on it or by stimulation of hyoid muscles. UA resistance was decreased 73 +/- (SE) 6% and 72 +/- 6% by traction and stimulation during expiration and 57 +/- 15% and 52 +/- 8% during inspiration. Moving averages of the geniohyoid (GH) and thyrohyoid (TH) obtained in six other dogs breathing 100% O2 showed phasic respiratory activity while the sternohyoid (SH) showed phasic respiratory activity in only two of these animals and no activity in four. With progressive hypercapnia, GH and TH increased as did SH when activity was already present. Airway occlusion at end expiration augmented and prolonged inspiratory activity in the hyoid muscles but did not elicit SH activity if not already present. Occlusion at end inspiration suppressed phasic activity in hyoid muscles for as long as in the diaphragm. After vagotomy activity increased and became almost exclusively inspiratory. Activity appeared in SH when not previously present. Duration and amplitude of hyoid muscle activity were increased with negative UA pressure and augmented breaths. We conclude that the hyoid arch and muscles can strongly affect UA flow resistance. Hyoid muscles show responses to chemical, vagal, and negative pressure stimuli similar to other UA muscles.

Effect of upper airway negative pressure on respiratory timing

The effects of upper airway negative pressure on respiratory timing and respiratory muscle activity were investigated in 13 urethane-pentobarbital anesthetized adult rabbits. Diaphragm and upper airway muscle EMGs were recorded with fine electrodes. The upper airway was converted into a closed system and negative pressure changes were made at will with a syringe attached to a laryngeal cannula. Both inspiratory and expiratory durations (Ti and Te) were prolonged during the negative pressure trials. Maximal prolongation occurred on the first experimental breath for Te and on second breath for Ti. Decreased effects were seen during maintained negative pressures. Peak diaphragm EMG and average slope of diaphragm EMG decreased during these trials. Diaphragmatic apnea (Te ⪖ 5 sec) occurred in 15% of trials. In some of these trials apnea lasted as long as the negative pressure stimulus whereas in others spontaneous breathing resumed after a period of apnea. Phasic upper airway muscle activity occurred during diaphragmatic apnea in most of these trials. The superior laryngeal nerve section markedly reduced the effects of negative pressure, indicating that its afferents primarily mediate this response. Our results suggest that upper airway negative pressure acts centrally on both inspiratory and expiratory timing as well as on the motor output of thoracic and upper airway respiratory muscles.