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Biomedical subjects

J A Daubenspeck

Publications and source records attributed to J A Daubenspeck.

At least 19 recordsLinked to original sources

Effect of perception of mechanical loading on human respiratory pattern regulation.

We applied external flow resistive (R) and elastic (E) mechanical loads over the entire respiratory cycle to five normal subjects by using a pseudorandom loading protocol. Loads ranged in magnitude from imperceptible (R0/E0) through just perceptible (R1/E1) to large (R2/E2) and resulted in respiratory pattern responses that were due to reflex responses alone (R0/E0) or to a combination of reflex responses and behavioral reactions to the perception of impeded breathing (R1/E1 and R2/E2). Pattern regulation dynamics were estimated from the computed impulse responses of tidal volume and inspiratory and expiratory durations. We anticipated that emergence of behavioral contributions would be marked by increased variability in response strategies and by increased nonlinearity in the observed responses. Regarding the immediate pattern response to loading, there was a tendency for increased qualitative variation across subjects as the load size increased, but the within-subject variability (coefficient of variation) was unaffected. We found no evidence for increased nonlinearity as loads became perceptible. The emergence of behavioral control in some instances seemed to be marked by reduction of complexity of the impulse response to one dominated by the zeroth-order lag, leading to dynamically simpler responses compared to control.

Adult

Immediate diaphragmatic electromyogram responses to imperceptible mechanical loads in conscious humans.

We used an esophageal electrode to measure the amplitude and neural inspiratory and expiratory (N TE) timing responses of crural diaphragmatic electrical activity in response to flow-resistive (R) and elastic (E) loads at or below the threshold for conscious detection, applied pseudorandomly to the oral airway of eight normal subjects. We observed a rapid first-breath neural reflex that modified respiratory timing such that N TE lengthened significantly in response to R loads in six of eight subjects and shortened in response to E loading in six of seven subjects. The prolongation of N TE with R loading resulted primarily from lengthening the portion of N TE during which phasic activity in the diaphragm is absent (TE NDIA), whereas E loading shortened N TE mainly by reducing TE NDIA. Most subjects responded to both types of loading by decreasing mean tonic diaphragmatic activity, the average level of muscle activity that exists when no phasic changes are occurring, as well as its variability. The observed timing responses are consistent in direction with optimally adaptive pattern regulation, whereas the modulation of tonic activity may be useful in neural regulation of end-expiratory lung volume.

Adult

Time course of laryngeal aperture response to expiratory resistance loading in humans.

Expiratory laryngeal restriction in normal humans is augmented immediately following expiratory flow resistance loading applied to the mouth. The time course of this increased narrowing reflects the dynamics of the physiological stimuli that govern laryngeal control during expiration. Lung volume, expiratory airflow and upper airway pressure are possible factors influencing the larynx, and a comparison of their dynamics with those observed for laryngeal narrowing during control and loaded expirations ought to indicate the possible contribution of each source. We examined the dynamics of lung volume, airflow and laryngeal aperture subsequent to single breath applications of small flow resistance loads (2 and 5 cm H2O.L-1.sec) in 3 subjects using video image analysis techniques to define accurately the laryngeal aperture variation with time. The earliest deviation of the loaded expired volume time course from the control trajectory lagged the earliest occurrence of a significant increase in laryngeal narrowing with the larger load. Augmented laryngeal narrowing occurred simultaneously with deviation of the expired flow from the control trajectory. The responses to the smaller load were noisier, but were consistent with the hypothesis that information other than lung volume modulates the early laryngeal response to these loads, and receptors responding to the rate of change of lung volume (airflow) and/or upper airway pressure may be involved.

Adult

Selective reflex activation of the genioglossus in humans.

In anesthetized or decerebrate animals, negative pressure applied to the upper airway selectively activates the hypoglossal nerve compared with the phrenic nerve. Conversely, positive pressure reduces hypoglossal nerve activity out of proportion to any change in the phrenic neurogram. We have tested the hypothesis that analogous pressure changes applied to awake humans would selectively inhibit or activate genioglossal electromyographic (EMGge) activity relative to diaphragmatic electromyographic activity (EMGdi). We studied seven normal subjects in a head-out body plethysmograph. Pressure at the mouth was either atmospheric, +10 cmH2O, or -10 cmH2O, and lung volume was held constant by applying an identical pressure to the body surface. Thus the transmural pressure distorting the respiratory system was applied only to the upper airway. Subjects breathed CO2-enriched (2-3%) room air to stimulate phasic respiratory EMGge activity. We found that -10 cmH2O pressure applied selectively to the upper airway resulted in a 49% enhancement of peak-integrated EMGge activity, but EMGdi activity remained at control levels. Positive pressure did not result in any changes in EMGge or EMGdi activity. Neither pressure resulted in significant changes in the magnitude or pattern of ventilation. We conclude that reflex mechanisms maintaining upper airway patency are demonstrable in awake humans and probably have an important role in moment-to-moment modulation of upper airway muscle activity in normal awake humans.

Adolescent

Targeted inspiratory muscle training improves respiratory muscle function and reduces dyspnea in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To examine the effects of targeted inspiratory muscle training on respiratory muscle function, clinical ratings of dyspnea, and perception of resistive loads in symptomatic patients with chronic obstructive pulmonary disease. DESIGN: Randomized, placebo-controlled trial with an 8-week treatment period. SETTING: Outpatient pulmonary clinic and pulmonary function laboratory. PARTICIPANTS: We studied 19 patients with moderate to severe chronic obstructive pulmonary disease, assigning 10 patients to an experimental group and 9 to a control group. INTERVENTIONS: Patients in both groups trained for 15 minutes twice each day using a device that provided breath-to-breath visual feedback of training intensity. Patients in the experimental group trained at six increasing levels of inspiratory resistance, whereas the patients in the control group trained at a constant, nominal level of resistance. MEASUREMENTS AND RESULTS: Although there was no statistically discernible difference in the effects of targeted muscle training on the mean difference in maximal inspiratory pressures between the two groups (9.83 cm H2O; 95% CI, -7.37 to 27.03), patients in the experimental group did show a significant increase in inspiratory muscle strength (15.03 cm H2O; P = 0.01). Experimental subjects also had decreased dyspnea after 8 weeks of training compared with control subjects (P = 0.003). Improvements in physiologic values and in dyspnea ratings were correlated. The perception of added resistive loads was not affected by inspiratory muscle training. CONCLUSIONS: Targeted inspiratory muscle training may enhance respiratory muscle function and reduce dyspnea in symptomatic patients with moderate to severe chronic obstructive pulmonary disease.

Aged

Human breathing pattern responses to loading with increased background impedance.

We determined the influence of the background level of mechanical impedance on the respiratory responses to very small mechanical loads, at or below the threshold for conscious perception. We used a pseudorandom load application technique to estimate the immediate pattern responses from the zeroth lag of the cross correlation between the load application sequence and the respiratory pattern components of tidal volume (VT), inspiratory and expiratory time (TI and TE), and the instantaneous respiratory frequency (f), minute ventilation (VI), and mean inspiratory flow (VT/TI). Elevation of the background resistance served to reduce the TI and TE responses to small perturbations in resistance from those in the control background state, which resulted in generally smaller perturbations of f, VI, and VT/TI. Elevation of the background elastance, however, served to initiate a TI reduction not seen in the control state but did not appreciably affect the rest of the pattern responses to the load perturbations. Thus the neural reflexes involved in breath-by-breath pattern regulation are modulated by the background level of the respiratory impedance, as well as by the type and size of the load perturbation.

Adult

Diaphragmatic electromyography using a multiple electrode array.

We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line.

Action Potentials

Measurement of respiratory sensation in interstitial lung disease. Evaluation of clinical dyspnea ratings and magnitude scaling.

To evaluate measurements of respiratory sensation in ILD, we compared ratings of breathlessness from three clinical scales with the perceived magnitude of added elastic loads in 20 symptomatic ILD patients. Dyspnea ratings were obtained by two independent observers for each clinical method. Perceived magnitude of four elastic loads was selected from the Borg category scale; these estimates were summarized using the psychophysical power function equation. Ten age-matched healthy subjects also scaled the magnitude of added elastic loads. Dyspnea ratings from the three clinical scales were significantly interrelated. Mean exponents for mouth pressure developed during elastic loading were similar in the patient and control groups. Dyspnea ratings and exponents for elastic loads were not significantly correlated in ILD patients. Of the physiologic parameters examined, Dsb and gas exchange during exercise correlated significantly with clinical dyspnea ratings; none correlated with the exponent for added elastic loads. These data demonstrate that clinical dyspnea ratings provide valid measures of breathlessness in patients with ILD which are independent of the perception of respiratory loads.

Dyspnea

An inexpensive servo-respirator based upon regulation of a shunt resistance.

We have designed and built an inexpensive servo-respirator for use in investigations of respiratory control in small animals. The device uses a butterfly valve to alter the resistance of an outflow shunt from a manifold that connects the animal's tracheal cannula to a pressure source. Tracheal pressure is regulated in response to a command provided by a suitably processed neural signal, often the integrated phrenic neurogram. As the valve opens, tracheal pressure approaches atmospheric; as it closes, tracheal pressure approaches the source pressure. An electronic controller circuit was developed to permit experimental procedures that include withholding volume delivery while maintaining a desired level of positive end-expiratory pressure. The device is able to track the neural command signal satisfactorily, and its performance appears to be limited primarily by the constraints applied by the respiratory system mechanics.

Airway Resistance

Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease.

To investigate the hypothesis that clinical methods and psychophysical testing provide different information about breathlessness, we compared dyspnea ratings from a modified Medical Research Council (MRC) scale, the Oxygen-Cost Diagram (OCD), and the Baseline Dyspnea Index (BDI) with the perceived magnitude of added loads in 24 patients with obstructive airway disease (OAD) who experienced dyspnea on exertion. Age of the patients was 55.8 +/- 13.7 yr (mean +/- SD), FEV1 was 1.77 +/- 0.81 L, and FEV1/FVC ratio was 52.6 +/- 10.5%. Dyspnea ratings were obtained for each clinical method by 2 independent observers; estimates of the magnitude of 5 resistive loads (10 to 85 cm H2O/L/s) were obtained using the Borg category scale (0 to 10). For comparative purposes, 12 age-matched (48.9 +/- 13.5 yr) healthy subjects were also studied. Clinical ratings of dyspnea obtained in patients for MRC (range, 0 to 4), OCD (range, 23 to 98), and BDI (range, 0.5 to 12.0) were all highly interrelated (rs = 0.79, -0.83, and -0.71; p less than 0.001 for all comparisons). Exponents of the psychophysical power function for resistive breathing loads were similar for patients with OAD (0.57 +/- 0.27) and control subjects (0.63 +/- 0.18) (p = NS). Clinical dyspnea scores were significantly correlated with both FEV1 and FVC; however, neither dyspnea ratings nor lung function were significantly related to the exponent for added breathing loads in the patient group. These comparisons indicate that in patients with symptomatic OAD, clinical methods for rating dyspnea are interrelated and are correlated with lung function, but are independent of perception of resistive breathing loads.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of non-REM sleep upon respiratory drive and the respiratory pump in humans.

We observed that ventilation fell and end-tidal CO2 rose in the change from wakefulness to non-REM (NREM) sleep in 4 normal human subjects studied on two nights each. We hypothesized that the observed ventilatory depression was due to effects of sleep both upon the central respiratory neural output and upon the mechanical respiratory pump. Both the central controller response to CO2, as measured by diaphragmatic and intercostal EMG activity, and the ability of the respiratory pump in effecting ventilation in response to diaphragmatic or intercostal activation, as measured by the relationship between the EMG activities and minute ventilation, are reduced in NREM sleep. We describe a general method of apportioning the separate effects of sleep, or other factors, upon the central respiratory controller, the respiratory mechanical pump, and the metabolic rate, in determining the total observed increase in end-tidal CO2.

Adult

Differential depression of hypoglossal nerve activity by alcohol. Protection by pretreatment with medroxyprogesterone acetate.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

Action Potentials

A noninvasive intraoral electromyographic electrode for genioglossus muscle.

We have developed an intraoral bipolar surface electrode for the genioglossus muscle. The electrode, made from an athletic mouthguard and dental impression material, was fitted to the lower teeth. Electrode wires, bared at the tip, were positioned on the bottom of the mouthpiece to lie in contact with the superior surface of the genioglossus just behind the teeth. The electromyographic activity of the genioglossus, simultaneously obtained from the surface electrode and conventional intramuscular electrodes, was compared during quiet breathing, CO2 rebreathing, and a variety of tongue movements. The two types of electrodes recorded similar patterns of muscle activity, and spectral analyses of the signals revealed similar and highly coherent frequency spectra. We conclude that the surface electrode satisfactorily reflects the bioelectrical activity of the genioglossus. The mouthpiece electrode has the further advantage that quantitative comparisons can be made among recordings made in different experimental sessions, since the fit of the mouthpiece to the teeth assures a constant relationship of the electrode to the genioglossus muscle.

Adult

Expiratory pattern and laryngeal responses to single-breath expiratory resistance loads.

Responses of expiratory duration (TE) and laryngeal aperture to small flow resistance loads (2 and 5 cm H2O/LPS) applied to single expirations were measured using repeated applications in four subjects during quiet breathing. All subjects significantly prolonged TE in response to the higher load and 3 of the 4 showed that same response to the lower load, which was not perceived by these subjects. These same 3 subjects showed a narrowed laryngeal aperture in response to loading such that their expiratory impedance must have been greater than the increase provided by the load alone. The effect of such a loading response was to slow the expiratory volume decay so that a small but significant increase in the halftime for volume decay was observed. The prolongation of TE seen with loading could be due to the alteration of volume-related feedback consequent to the increased expiratory impedance. This may serve a role in regulation of expiratory muscle function.

Adult

Immediate human breathing pattern responses to loads near the perceptual threshold.

Breathing pattern responses to small mechanical loads added pseudorandomly to the external airway of human subjects were measured using flow-resistive and elastic loads above and below the threshold for detectability of some subjects. The zeroth lag of the computed cross-correlations between the loading sequence and the various aspects of the breathing pattern response was used as an index of the immediate response to loading. All subjects showed an immediate reduction in tidal volume (VT) and expiratory duration (TE) in response to elastic loading, but inspiratory duration (TI) responded variably. Respiratory frequency (f) was increased, and minute ventilation (V) and mean inspiratory flow (VT/TI) decreased immediately in all subjects. Resistance loading, on the other hand, tended to prolong TI and TE immediately such that f fell. VT responses were variable, and both V and VT/TI fell. The responses to imperceptible loads reflect mainly the action of neural reflexes and characteristics intrinsic to the respiratory muscles and configuration of the chest and abdomen. A mathematical simulation was used to show that the TE responses in particular may indicate the action of subconscious neural reflexes.

Differential Threshold