Respiratory-related evoked potential and upper airway transmural pressure change by using the negative expiratory pressure (NEP) device

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Abstract

Objective: Several studies have previously shown respiratory related evoked potentials (RREP) in humans elicited by mechanical stimuli applied on upper airways (UA). According to us, heterogeneous findings, concerning latencies and amplitudes, have been reported because of the different timing of stimuli application during the respiratory cycle and/or features of pressure stimuli. Therefore we evaluated the cortical response evoked by transmural pressure changes at the mouth induced by a negative expiratory pressure (NEP) device.

Methods: RREP were recorded in 22 healthy non-obese, non-snoring volunteers. The subjects were studied awake in seated position during quiet breathing. Three different pressure levels were applied, in a random order, 200 ms after the beginning of expiration. Cortical electrical responses were recorded from scalp electrodes at Fz, Cz, and Pz scalp location (international 10–20 system) referenced to the linked earlobes.

Results: RREP responses consisted of two negative (N45, N120) and two positive (P22, P85) waves. There was no significant effect of pressure or electrode on component latencies. The P22 wave (PRESSURE: F(df2,42)=6.66, P<0.01), the N45 wave (PRESSURE: F(df2,42)=16.51, P<0.001), and the P85 wave (PRESSURE: F(df2,42)=15.15, P<0.001) increased significantly theyr amplitude with increasing from pressure stimuli 1 to 10 cmH2O.

Conclusions: The present results suggest that the UA NEP application in humans is a reliable way of evoking cortical responses. The experimental features that we described allow us to minimize the confounding factors in evaluating RREPs. The NEP device appears to be a useful tool for investigation of the neurobiology of UA sensation in humans.

Introduction

Psychophysical studies on respiratory load sensations have demonstrated that the detection and magnitude estimation of respiratory loads is similar to other muscle systems (Killian et al., 1981, Stubbing et al., 1981, Tack et al., 1981). The fact that humans are consciuosly aware of breathing against mechanical loads suggests activation of neurons in the cerebral cortex and that this activation should be measurable. Using evoked-potential techniques, several studies have shown the activation of cortical neurons in humans induced by mechanical stimuli applied on upper airways (UA). More recently it has also been shown that airway pressure changes can be consciously perceived (Williams et al., 1988). Davenport et al. (1986) first recorded respiratory related evoked potentials (RREPs) to inspiratory occlusions and observed that the latency was inversely related to the respiratory drive. Revelette and Davenport (1990) demonstrated that a midinspiratory occlusions resulted in RREPs shorter in latency and larger in amplitude than those obtained to occlusions presented at the start of inspiration. An increase in RREP amplitude related to the magnitude increase of inspiratory pressure at the mouth was observed by means of resistive loads at the mouth (Knafelc and Davenport, 1997). RREPs have been also obtained without occlusion maneuver, by means of a negative pressure applied at the mouth in early inspiration (Strobel and Daudenspeck, 1993). These authors showed that amplitude varied directly, and component latencies inversely, as a function of pulse magnitude. More recently Hammond et al. (1999) elicited RREP using positive pressure generated by an expiratory occlusion. These controversial reported results may be explained by differences in timing of stimuli application during the respiratory cycle and/or features of pressure stimuli. Although different stimuli have been used by these authors, an upper airway transmural pressure change was determined in all these studies.

Due to physiological changes during the respiratory cycle the expiratory phase is characterized by a neural drive relatively constant within experimental session and across subjects. Valta et al. (1994) developed a device that allows the application of negative expiratory pressure (NEP) at the mouth during a tidal expiration. The NEP device, firstly employed to analyze the airway flow limitation in patient with respiratory disease, has also been successfully used to study genioglossus muscle reflex activity in awake humans (Tantucci et al., 1998). The stimuli delivered have a very steep pressure increase (i.e. 7 ms) with a square wave shape highly reproducible in rise time and pressure values. In addition the NEP device acts without added resistive load or occlusion maneuver. These experimental features allow minimization of the confounding factors in evaluating respiratory-related potentials elicited by transmural pressure changes.

We therefore evaluated, in awake healthy humans during quiet breathing, the cortical response to transmural pressure changes at the mouth by using a NEP device.

Section snippets

Subjects

We studied 22 healthy volunteers (age range 27–47 years, 12 men and 10 women). Subjects met the following inclusion criteria: (1) no obesity; (2) no history of neurologic, cardiac or pulmonary diseases; (3) no habitual snoring, confirmed by bed partner; (4) no daytime sleepiness. After a description of the protocol informed consent was obtained before testing. The study was approved by the local institutional committee.

NEP device

Flow (V′) was measured with a Hans Rudolph pneumotachograph with a ±2.6 l/s

Results

All the subjects recruited successfully completed the scheduled experimental protocol. Pressure pulses resulted in reliable reproducible changes in Pm. The actual range values of NEP at the mouth during −1, −5, and −10 cmH2O runs were −1.0, −0.5; −4.5, 5.5; and −9.5, 10.5; respectively.

The pressure at the mouth profile as well as cortical responses evoked by NEP are plotted on the same time scale in Fig. 1. For descriptive purpose we consider the waveform at Cz. The onset of the early response

Discussion

Due to physiological changes in neural drive during the respiratory cycle, the timing of pressure stimuli application to upper airways appears to be relevant in evaluating cortical evoked potentials. It has been observed that the neural drive is greater during inspiration than during expiration. Actually, the electromyographic findings of upper airway (UA) muscles, obtained in awake humans during quiet breathing, have shown an EMG pattern characterized by an inspiratory increase followed by an

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