Title: Effect of ventilatory loads on respiratory mechanics and dyspnea
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Title: Effect of ventilatory loads on respiratory mechanics and dyspnea
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Creator: Knafelc, Marie E
Copyright Date: 1992
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EFFECT OF VENTILATORY LOADS ON
RESPIRATORY MECHANICS AND DYSPNEA













By

MARIE E. KNAFELC


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA


1992


















TABLE OF CONTENTS



ACKNOWLEDGEMENT .................. ................... iv


ABSTRACT .................. ................... ......... v


INTRODUCTION ................... ................... .... 1


REVIEW OF THE LITERATURE ................... ............ 3


Mechanical Effects of Ventilatory Loads . ... .. . .. .. .. 3
Mechanical Changes and Perception of Ventilatory Loads . .. .. .. 6
Perception of aVentilatoryLoad ................... ....... 9
Neural Paths for the Perception of a Ventilatory Load . ... . 13
Hypothesis ........., ......................... 17

MEDTHOD ........., ............................... 18


Subjects ........., ........................... 18
Protocol ........., ........................... 18
Respiratory Related Evoked Potentials .. . ... .. .. .. 18
Analysis ........., ................... 23

RESULTS AND DISCUSSION .........,, .................. 25


Results ........., ............................ 25
Study 1 ........., ....................... 25
Study 2 ........., ...................... 26
Study 3 ..................................,,,. 28
Discussion ........., ......................... 40
Summary Statement .........,, ................ 40
Relationship Between Load Application Timing and
Magnitude Estimation ...................... 40
RREP and Resistive Loads ................... ...... 42

RREP, Pdi, and Magnitude Estimation . .. .. .. .. .. 44
Model for Behavioral Compensation to a Respiratory
Load .................................... 47











SUMMARY AND CONCLUSIONS ................... ........... 51


Summary ................... ................... .... 51
Conclusions ................... ................... .. 51


APPENDIX SUBJECT DATA IN RESPONSE TO A RESISTIVE LOAD .. 53


REFERENCE LIST ................... ................... ... 56


BIOGRAPHICAL SKETCH ................... ................ 64













ACKNOWLEDGEMENTS


I would like to thank the members of my committee for their patience in
developing a doctoral program that satisfied my professional needs and fulfilled the
requirements of the graduate school.
I have a special thanks for my mentor, Dr. Paul W. Davenport. Through his
guidance, I learned the techniques for investigating the perception of ventilatory
loads, and more importantly, he taught me the philosophy of science in the proud
tradition of his mentor; specifically, how to ask questions and enjoy finding the
answers. As he expressed in the photograph he presented me after my defense,
there's always another mountain to climb such a beautiful sight.
Finally, I thank my God who directs my paths and gives me strength as 1
yield myself into His hands.













Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Philosophy

EFFECT OF VENTILATORY LOADS ON
RESPIRATORY MECHANICS AND DYSPNEA

By

Marie E. Knafelc

August 1992


Chairperson: James E. Graves
Major Department: Health and Human Performance

The purpose of this study was to determine the relationship between

resistive load magnitude and the transdiaphragmatic pressure (Pdi), the P1

amplitude of the respiratory related evoked potential (RREP), and the magnitude

estimation (ME) of the load. A series of 3 experiments was performed. The first

study determined the effect of the timing of an inspiratory interruption on the ME

of a resistive load. Five different resistances were randomly presented at either the

onset of inspiration or during midinspiration. The subject reported the ME for the

load using a modified Borg scale. The second study determined if the RREP P1

amplitude changed with inspiratory resistive loads. The subject's RREPs were

recorded in response to 3 different resistive loads and a control breath. The loads

and control breaths were presented in random order using a latin square design.








The third experiment followed the same protocol as the second study. In addition

to measuring the RREP, the Pdi, and ME for the load were recorded. The log-log

plot of the group averaged data from the first study showed that the timing of the

load presentation did not affect the subject's sensitivity to the load. In the second

and third study, the group mean patterns of the RREP P1 amplitude, Pdi, and ME

significantly increased with increases in the resistive load. A log-log plot of the

group averaged P1 amplitudes and Pdi showed a direct linear relationship with

ME. The power functions observed for Cz-C3 and Cz-C4 P1 amplitudes and Pdi

to ME were 1.3, 1.8, and 1.8, respectively. Pdi had a direct linear relationship with

Cz-C3 and Cz-C4 with the power functions of 1.4 and 1.0. These results were

consistent with the hypothesis that the magnitude of the respiratory load sensation

was related to Pdi and the P1 amplitude of the RREP.













INTRODUCTION


It is well known that humans can perceive ventilatory loads and modify their

breathing pattern in response to that load. Zechman and Davenport (1978)

reported temporal differences in the detection of resistive and elastic loads that

were related to the pattern of sensory information unique to an elastic or resistive

inspiratory load. In addition, Zechman, Wiley, and Davenport (1981) showed that

humans used the information's temporal pattern for the detection and

discrimination between those loads.

Subsequent experiments attempted to elucidate the afferents responsible for

load detection. The study by Zechman, Muza, Davenport, Wiley, and Shelton

(1985) suggested that the diaphragm's afferents monitoring the changes in

diaphragmatic tension, as represented by the transdiaphragmatic pressure (Pdi),

mediated the response. They reported a correlation between the load detection

latency and the Pdi

Davenport, Friedman, Thompson, and Franzen (1986) demonstrated, in

humans, respiratory related neurogenic activity within the somatosensory region

of the cerebral cortex during a momentary inspiratory occlusion. Their results

demonstrated a respiratory load dependent activation of the somatosensory cortex

similar to the evoked responses obtained by mechanical stimulation of afferents in










the hand and ankle. However, the relationship of the respiratory related evoked

potential (RREP) to the perception of a ventilatory load was not determined.

The purpose of this study was to determine the relationship between the

resistive load magnitude and the transdiaphragmatic pressure and P1 amplitude

of the RREP.













REVIEW OF THE LITERATURE


Mechanical Effects of Ventilatory Loads


Cain and Otis (1949) demonstrated a decrease in minute ventilation when

breathing against a continuous resistive load. At low inspiratory resistance,

breathing frequency (f) is decreased, and at high resistive loads, f and tidal volume

(VT) are decreased (Dressendorfer, Wade, & Bernauer, 1977). The reduction in

f and VT is accompanied by a decrease in the inspiratory flow (VT/TI) due to a

prolongation of the inspiratory time (TI) (Daubenspeck, 1981) associated with a

prolonged and decreased rate of rise in the diaphragm's electromyogram (EMGdi)

(Lopata, Onal, & Ginzburg, 1983). When breathing against inspiratory elastic

loads, similar changes in the breathing pattern are observed except there is a

greater decrease in VT to cause the decrease in flow (Poon, 1989b).

When breathing against a resistance, there is a load-compensatory reflex

whose primary function is to stabilize the rib cage (Shannon & Zechman, 1972).

The rib cage and abdominal muscles are recruited and perform more mechanical

work than previously estimated as ventilation is increased (Goldman, Grimby, &

Mead, 1976). This interaction between the diaphragm and rib cage muscles

results in changes in the transdiaphragmatic pressure (Pdi) that are greater than










the changes in EMGdi (Ginzburg, Lopata, & Onal, 1989). Thus the role of the rib

cage muscles is to place the diaphragm, the primary pump for ventilation, at the

optimal position on its length-tension curve for pressure development (Grimby,

Goldman, & Mead, 1976). Any change from that optimal position results in a

decrease in inspiratory muscle performance (Eldridge & Vaughn, 1977).

Pdi is greater for an inspiratory resistive load compared to the same EMGdi

response for an unloaded breath (Lopata et al., 1983). Therefore, maximum

power, force, and velocity is achieved by the appropriate recruitment of the various

muscle groups due to the arrangement of the inspiratory musculature (Macklem,

Macklem, & DeTroyer, 1983). Fatigue of the rib cage muscles results in the

subject's inability to sustain a target mouth pressure because the mean maximum

diaphragmatic pressure does not decrease during exhausting inspiratory loads

(Hershenson, Kikuchi, Tzelepis, & McCool, 1989). Thus the activation of the rib

cage muscles, which work synergistically with the diaphragm, ensures chest wall

stability (DiMarco, Supinski, & Budzinska, 1989) so that the diaphragm can

effectively pump air.

A common factor in the ventilatory response to added resistance is the

algebraic difference between peak inspiratory and peak expiratory pressure of 100

cmH20 (Cerretelli, Sikand, & Farhi, 1969). The reduction of the peak inspiratory

pressure while maintaining the same breathing frequency is accomplished by

increasing the inspiratory duration (Jones, Killian, Summers, & Jones, 1985).










These observations suggest that detecting and modulating pressure changes are

important aspects of load compensation.

Otis, Fenn, and Rahn (1950) demonstrated that breathing pattern is adjusted

to minimize the work of breathing. Work is the product of the force applied to an

object and the resultant displacement of that object. For the respiratory system,

force is equivalent to the pressure that generates an airflow, and displacement is

the volume of air moved for that amount of pressure. The purpose for altering a

breath is to reduce the amount of pressure generated or limit the tidal volume that

will lower the work of the respiratory apparatus. Mcllroy and Christie (1954)

considered that an increase in respiratory work may be an important factor in

limiting a person's maximal breathing capacity. However, a person's ventilatory

response becomes less dependent upon the calculated work of breathing when

exercising at high work rates and breathing against a resistive load, (Demedts &

Anthonisen, 1973).

The increase in the oxygen consumption rate attributed to breathing against

a ventilatory load is associated with the respiratory muscles' contractile machinery

(Campbell, Westlake, & Cherniak, 1959; Shannon & Zechman, 1972). This oxygen

cost for ventilation is reflected by the amount of tension developed by the

diaphragm as a function of time, rather than pleural pressure or the work of

breathing (Field, Sanci, & Grassino, 1984). Furthermore, there is a volume-

dependent oxygen cost for the pressure generated by the inspiratory muscles

(Dodd, Collet, & Engel, 1988). These studies suggest that changes in the










ventilatory pattern and recruitment of the rib cage muscles to maintain

diaphragmatic efficiency are related to the pressure generation necessary to

maintain an adequate tidal volume (Ginzburg, Lopata, & Onal, 1989).

Zechman, Hall, and Hull (1957) applied resistive loads to each phase of

ventilation. They reported that an expiratory resistive load caused a greater

reduction in flow and f than an inspiratory load. Neither Pdi nor the EMGdi were

significantly altered during the expiratory resistive load (Barnett & Rasmussen,

1988). During inspiratory flow-resistive loading, changes in the Pdi predominate

over changes in force generated by all the inspiratory muscles. Therefore

increases in Pdi during loaded breathing results in changes in the breathing pattern

to accommodate the increased load (Lopata et al., 1983). These studies suggest

that the diaphragm's afferents mediate the compensatory ventilatory response.

Changes in breathing pattern must be a balance between the mechanical

work performed by the respiratory apparatus and the chemical drive (Hof, West,

Younes, 1986; Poon, 1989a). It appears that the diaphragm and its ability to

generate pressure for a given lung volume are the factors involved with the

immediate response to a ventilatory load and possibly to the perception of the

load.


Mechanical Chanqes and Perception of Ventilatory Loads


Inspiration against an increase in mechanical load elicits a sensation of

breathlessness. Campbell, Freedman, Smith, and Taylor (1961) suggested that










detection of elastic loads was correlated to changes in volume (length) and

pressure (tension). When breathing against a nonelastic load, a dynamic

component also is involved along with length-tension appropriateness (Bennett,

Jayson, Rubenstein, & Campbell, 1962). Furthermore, the ability to distinguish

between the two types of loads implies the capability to differentiate the mechanical

pattern differences (Campbell, Bennett, & Rubenstein, 1963; Zechman, Wiley, &

Davenport, 1981). The respiratory muscles and the costovertebral joints have

mechanoreceptors that can provide the sensory information needed for load

related afferent coding of pump mechanics and detection (Campbell & Howell,

1962).

The perceived magnitude of an inspiratory load is directly related to the

force generated by the respiratory muscles and indirectly to the load itself

(Stubbing, Ramsdale, Killian, & Campbell, 1983). Thus the respiratory related

afferents monitoring breathing probably detect a change in breathing pattern rather

than the awareness of the ventilatory stimuli resulting in the perception of the load

(West, Ellis, & Campbell, 1975).

The mechanoreceptors in the respiratory apparatus are exquisitely sensitive

to the mechanical parameters related to ventilation. Small changes in tidal volume

can be perceived regardless of inspiratory time, initial tidal volume, or posture,

which suggests that pressure, as a function of volume, may provide a signal for

volume perception (Fogarty, Murphy, Heyer, & Fishman, 1978). To sense tidal

volumes accurately, there must be afferent information related to both lung volume










and respiratory muscle tension (Wolkove, Altose, Kelsen, Kondapalli, & Cherniak,

1981), which comes from receptors affected by respiratory muscle contraction

(Stubbing, Killian, & Campbell, 1981).

Elastic and resistive loads can be sensed and distinguished from one

another suggesting that load related changes in breathing patterns are generated

by afferents in the respiratory apparatus (Zechman et al., 1981). The ability to

separate between the two types of loads depends upon the temporal patterning

of the sensory information, with resistive load detection being flow dependent, and

elastic load detection being volume dependent (Zechman & Davenport, 1978).

Detecting flow changes early during an inspiration along with volume

information contribute to load perception and load differentiation (Killian, Mahutte,

Howell, & Campbell, 1980). Together, tidal volume, flow rate, and their related

muscular effort may contribute to the sensation elicited by loaded breathing (Killian,

Mahutte, & Campbell, 1981). Without specifying the particular afferents, it can be

concluded that resistive load detection relies on flow-related sensory information,

and elastic load detection relies on volume-related sensory information (Burki,

1981). The perception of the load is directly related to the inspiratory muscle force

and its duration within the breath to which the load is applied (Killian, Bucens, &

Campbell, 1982). The same respiratory muscle afferents related to force

generation are used to estimate the magnitude of both inspiratory and expiratory

loads (Muza, McDonald, & Zechman, 1984).










It has been suggested that awareness of the efferent motor commands may

contribute to the estimation of respiratory loads (Gandevia, Killian, & Campbell,

1981). And awareness of both efferent inspiratory and expiratory motor

commands has been implicated in the perception of breathlessness (Chonan,

Altose, & Cherniack, 1990). Thus the body may utilize the magnitude of sensory

information and the efferent motor command to the respiratory pump to estimate

the size of the load (Killian, Gandevia, Summers, & Campbell, 1984).

However, the extent of the contribution of efferent information to respiratory

sensation is unclear. An increase in diaphragmatic activation does not accompany

the increased perception of respiratory effort during fatiguing diaphragmatic

exercise (Ward, Eidelman, Stubbing, Bellemare, & Macklem, 1988). But the

outgoing command may not be restricted to the diaphragm. Instead, there also

may be an increased awareness of the recruitment of the accessory muscles of

respiration that contribute to the sensation of dyspnea (Breslin, Garoutte, Kohiman-

Carrieri, & Celli, 1990). From these reports, the perception of a ventilatory load

probably depends on several mechanisms involved in the regulation of breathing

(Chonan, Mulholland, Leitner, Altose, & Cherniack, 1990) with maintenance of

diaphragmatic function playing a major role.


Perception of a Ventilatory Load


Psychophysics is a methodology that relates the subjective interpretation of

sensory information to a physical stimulus. The classical studies by Weber in 1846










reported that the perceived intensity of a stimulus is a constant fraction of the

background intensity (Weber's fraction). This relationship means that the subject

detects a change in stimulus level as a function of the background stimulus.

Because of the intersubject variability of their internal ventilatory loads, the Weber

fraction provides a better index of load detection.

Threshold measurements of load detection are the difference between

control breaths, which include the internal resistive and elastic loads and the

minimal resistance of the breathing circuit, and the loaded breath. Wiley and

Zechman (1966) reported that perception of airflow resistance was constant when

expressed in terms of a ratio of added resistance over the initial background

resistance. The Weber fraction rises sharply when resistances were added to low

background resistances, a finding similar to other sensory modalities (Stubbing,

Killian, & Campbell, 1983).

Zechman et al. (1981) demonstrated that normal subjects cannot

discriminate between resistive and elastic loads that are near their detection

threshold. Only when those loads were increased to 4-5 times above the threshold

level was the subject able to accurately discriminate between the load types. In

addition, Zechman and Davenport (1978) reported temporal differences in

detection of elastic and resistive loads. Therefore, discrimination between resistive

and elastic loads depends upon the magnitude of the stimulus and the temporal

patterning of that information.










Subjects can also provide a report of the perceived magnitude of a stimulus,

which when plotted against the stimulus intensity demonstrates a relationship

between perception and the stimulus. Stevens (1957) proposed that this

relationship was a logarithmic function for sensory modalities and was linear when

plotted on a log-log scale. The slope of this line represented the relative sensitivity

of the subject to the applied stimulus, Steven's power function (Stevens, 1970).

Power functions provide information regarding the sensory processing of the

stimulus, although the coefficients' value is highly dependent upon experimental

conditions (Harver & Mahler, 1990). Specifically, the power function governs the

growth of neuroelectric events involved with sensing a stimulus (Stevens, 1970).

Skeletal muscle mechanoreceptors follow Steven's power function and can

contribute to perception of a mechanical load (Roland & Ladegaard-Pedersen,

1977).

The respiratory muscles have a power function of 1.6 relating magnitude

estimation to added inspiratory work (Gamberale, Holmer, Kindblom, & Nordstrom,

1978). This exponent is characteristic of the power function of other large skeletal

muscle groups (Stevens & Mack, 1959). Hence, similar afferent information is

used to detect ventilatory loads as any other skeletal muscle groups.

Magnitude estimation can be obtained by different techniques. Category

scales provide nominal data, which are verbal in nature, and are the simplest form

of response variable (Marks, 1982). They are advantageous because they provide

references for the subject to use when making a judgement. Ratio scales have the










subject relate his or her perception of the physical stimulus in direct proportion to

their subjective intensity of the stimulus. These scales avoid the problem of

category scales, but they do not provide a means to make direct comparisons

between individuals. Borg (1982) proposed a category scale with ratio properties,

the modified Borg scale, which combines the 2 scales and has been used for

evaluating breathing difficulties.

Cross-modal comparisons provide a consistent scale of apparent force

derived from different scaling procedures. For example, since the power function

of apparent heaviness of a weight is the same as the apparent force of a handgrip,

one sensory modality can be used as a comparison procedure for another

modality (Stevens & Mack, 1959). In essence, "equal stimulus ratios produce

equal sensation ratios," (Stevens, 1970). The benefit of this technique is it can be

used as an alternative to numerical scales.

Using cross-modality techniques, in particular the hand grip response to a

breathing load, Zechman et al. (1981) graphically demonstrated that subjects could

mimic with handgrip, the pattern of resistive and elastic load detection. The hand

grip response to a resistive load traced the changes in inspiratory flow rate;

whereas, elastic loads followed the changes in inspiratory volume. It was

concluded that resistive load detection was flow dependent, and elastic load

detection was volume dependent.

Steven's power function can be used to evaluate the relationship between

the intensity of the physical stimulus on the sensory apparatus and the perceived










sensation for that sensory modality. Similar power functions for the perception of

tidal volume and inspiratory flow suggest that they are sensed by the same

physiological mechanism (Stubbing et al., 1981). Based on the evaluation of the

power function, it was proposed that the magnitude estimation of added inspiratory

and expiratory loads used similar muscle receptors and neural processing (Muza

et al., 1984, Chonan et al., 1990). And magnitude estimation of ventilatory loads

was directly related to the inspiratory force and its duration (Killian et al., 1982).

In summary, the perception of a ventilatory load utilizes sensory modalities

similar of those of other large muscle groups (Gamberale et al., 1978). The

temporal relationship of the intensity of that sensory information related to the force

or pressure generated is used to detect and discriminate loads to breathing

(Zechman & Davenport, 1978).


Neural Paths for the Percep~tion of a Ventilatory Load


The compensatory response to a ventilatory load involves processing

afferent information which results in a motor response. Bennett et al. (1962)

recorded the mechanical changes that occurred with added nonelastic loads.

They proposed that receptors in the chest wall mediated the sensation of breathing

against a load. Davis (1967) compared patients with upper spinal cord lesions to

normal controls and concluded that the somatic receptors, possibly the thoracic

joint receptors, contributed to the ability to detect a resistive load.










However, with anesthesia of the vagi, Guz, Noble, Widdicombe, Trenchard,

Mushin, and Makey (1966) suggested that vagal afferents were responsible for the

sensation of dyspnea during a breath-hold maneuver, though detection and

perception of elastic loads were unaffected. The vagus carries afferent fibers of

pain and touch from the mucosa of the posterior soft palate to the trachea (Clark,

1975), bronchi, bronchioles, and the alveolar interstitium (Paintal, 1977). Patients

with a cervical transaction at the C3 level were able to detect a resistive load

though their background resistance was not taken into account (Noble, Frankel,

Else, & Guz, 1971). Transection of the spinal cord at this level essentially

deafferents the chest wall and diaphragm. Noble, Frankel, Else, and Guz (1972)

reported that patients with cervical lesions from C3 down to C6 had normal

sensations to resistive loads and concluded that chest wall and diaphragmatic

mechanoreceptors were not essential for load detection. Furthermore, increases

in inspiratory volumes do occur with vagally mediated augmentation of phrenic

nerve activity (Pack, DeLaney, & Fishman, 1981).

Conclusions from a patient population do not necessarily apply to the

normal population. When the afferents of the chest wall were blocked with spinal

anesthesia to the T1 level (Eisele, Trenchard, Burki, & Guz, 1968) along with

anesthesia of the upper and lower airways (Bakers & Tenney, 1970), it became

evident that in normal subjects the diaphragm was the main site for load detection

(Chaudhary & Burki, 1978). Specifically, the diaphragm's mechanoreceptors are










responsible for the perception and for the magnitude estimation of resistive and

elastic loads (Burki, Davenport, Safdar, & Zechman, 1983).

Changes in diaphragmatic tension, represented by the Pdi, may provide the

sensory information about the inspiratory load (Zechman, Muza, Davenport, Wiley,

& Shelton, 1985). Even during normal breathing, the diaphragm's

mechanoreceptors modulate the central respiratory activity of the diaphragm (Oyer,

Knuth, Ward, & Bartlett, 1989). Furthermore, the diaphragm contains several

different receptors that transduce muscle length and provide the central nervous

system with proprioceptive information (Holt, Dalziel, & Davenport, 1991).

The diaphragm is innervated by motor and sensory fibers of the phrenic

nerve. Davenport, Thompson, Reep, and Freed (1985) stimulated a cat's phrenic

nerve and elicited a cortical response. The cortical evoked potential was

recorded in the cat somatosensory cortex. This activity demonstrated a fast

conducting pathway for the diaphragm's afferents to the somatosensory region of

the cerebral cortex.

The cortical evoked potential in humans has a waveform consisting of 4

components; an initial positive complex, followed by a negative, positive, and then

negative deflection. The first positive complex (Pl) may represent an early

cognitive potential related to the thalamocortical projection to the somatosensory

cortex (Desmedt, Huy, & Bourguet, 1983). The P1 amplitude of the CEP may be

related to the neural response to the stimulus intensity (Franzen & Offenloch,

1969). The neurogenic activity related to an inspiratory occlusion was recorded










with electrodes placed over the human somatosensory cortex (Davenport,

Friedman, Thompson, & Franzen, 1986). The peak P1 latency of the respiratory

related evoked potential (RREP), which be recorded bilaterally, includes the time

from when the subject generates the stimulus during an inspiratory occlusion till

it reaches the somatosensory cortex (Revelette & Davenport, 1990).

For a ventilatory response to a load to occur, the sensory information must

be followed by a motor response. When inspiration is occluded and the mouth

pressure is recorded at 0.1 sec after the occlusion, an index of the overall motor

output from the respiratory center can be obtained (W~hitelaw, Derenne, & Milic-

Emili, 1975). Measuring the mouth pressure within 0.1 and 0.15 sec of an

occlusion (PO.1 ) eliminates any artifact from a reflexive augmentation of the breath

and closely parallels the changes in phrenic nerve activity (Evanich, Lopata, &

Lourenco, 1976).

The phrenic nerve efferents provide the motor innervation of the diaphragm,

and the diaphragmatic electromyogram (EMGdi) is a measure of phrenic nerve

activity. Lopata, Onal, Evanich, and Lourenco (1980) found differences between

the PO.1 and the EMGdi and suggested that conscious factors caused the

additional force generation by the recruitment of accessory muscles during flow

resistive breathing. This conscious awareness of the motor command may

contribute to the perception of the load (Gandevia et al., 1981).

The efferent copy theory suggests that a central collateral discharge to the

sensory cortex causes the sensation of effort (Killian & Campbell, 1990). In










concept, a copy of the motor drive to the pump is made in the higher brain centers

and serves as the template for comparison with the sensory feedback from the

respiratory apparatus. When the load sufficiently alters the diaphragm's function,

the pattern of sensory feedback is changed to a level that elicits an error signal

from the comparator system. This error signal then leads to the detection of the

load and subsequent behavioral compensation. In essence, the motor drive to the

respiratory apparatus facilitates load sensation, and perception of the load alters

the motor drive.

The control of ventilation is often considered a brainstem function.

However, the afferents projecting to the somatosensory cortex and the efferents

from the motor cortex stimulating the human diaphragm (Gandevia & Rothwell,

1987) can provide a behavioral component to ventilation (Murphy, Mier, Adams,

& Guz, 1990).

Behavioral compensation and detection of a ventilatory load involve cortical

control. The evidence to date strongly suggests that the diaphragm's

mechanoreceptors subserve that response.




Hypothesis


The magnitude of the respiratory load sensation is related to the

transdiaphragmatic pressure and the P1 amplitude of the respiratory related

evoked potential.













METrHOD


Subjects


Adult subjects free of any known pulmonary or neurological disease were

recruited to participate in this study. Each subject was informed of the general

nature of the study and signed a statement of consent. The Institutional Review

Board, J. Hillis Miller Health Center, University of Florida reviewed and approved

the protocol. The subjects used in the water study had their forced vital capacity

(FVC), peak expiratory flow, and forced expiratory volume in 1 second (FEV1)

measured prior to the study to ensure that the subject's pulmonary parameters

were within 80% of the predicted values.



Protocol


Respiratory Related Evoked Potentials

The subject was read a standard set of instructions prior to the start of the

experiment.

Three experiments were performed evaluating the effect of inspiratory

resistive loads on the RREP and magnitude estimation (ME). The first study

investigated the effect of timing of the interruption on the ME of graded inspiratory










loads. Previous studies demonstrated that midinspiratory occlusions resulted in

a larger RREP compared to an onset inspiratory occlusion (Revelette & Davenport,

1990).

Five men and 4 women, whose average age was 26 years with no history

of pulmonary disease, participated in the first protocol. Five magnitudes of

inspiratory resistance (R), (2, 5, 9, 13, and 21 cmH20/L/sec) were presented

either at the onset of an inspiration or at midinspiration. The subject was seated

comfortably in a lounge chair and respired through a mouthpiece connected to a

nonrebreathing valve. The response variable, ME, was obtained by using a hand-

held meter with a modified Borg scale (Borg, 1982). An inspiratory load was

presented after 3 to 6 uninterrupted breaths. The subject was visually cued for the

loaded breath with a light on the meter. The load magnitudes were randomized

in a complete repeated measures design. A minimum of 10 presentations for each

load magnitude was performed. The experimental session was divided into 2

trials with 5 presentations of each load in each trial.

The second experiment evaluated the effect of different inspiratory

resistance magnitudes on the RREP P1 amplitude. Four women and 2 men,

whose average age was 24 years with no history of pulmonary disease,

participated in this protocol. Surface cup electrodes were placed at the scalp

positions Cz, C3, and C4 (according to the International 10/20 system). The

ground was attached to the left earlobe. All the surface impedances were checked

and adjusted until the impedances were below 3 kohms. The scalp electrodes










were connected to a multiplexer, and the signals (G2 positive) were filtered (0.3 Hz

- 3 kHz) and amplified X200,000 (Grass Instruments, model 12 Neurodata

Acquisition System, Quincy, MA).

The subject wore a nose clip and breathed through a mouthpiece

connected to a nonrebreathing valve. Care was taken to suspend the valve to

eliminate the need for the subject to bite the mouthpiece yet maintain an airtight

seal. The inspiratory port was connected to a resistive loading manifold with three

resistive loads: 2, 9, and 21 cmH20/L/sec. The manifold was hidden from the

subject's view. Mouth pressure (P,), measured in cmH20, was recorded from

a port in the center of the valve. Pm was displayed on an oscilloscope and used

for timing the interruption. A balloon occluder was inflated to block the unloaded

port and channel the inspiratory airflow through the port for the added load. The

balloon pressure was used to trigger the signal average. All loads were presented

at midinspiration. Three to 6 unoccluded breaths proceeded the loaded breath.

The subject was given a series of detectable loads prior to the experimental

trial to provide them with a standard opportunity to experience the load sensation

when known loads were added. The subjects were seated in a recliner and

instructed to relax all postural and facial muscles and to breathe as normally as

possible. The subject listened to music of his or her choice to prevent artifacts

related to auditory cues. The subjects were also asked to close their eyes to

reduce visual distractions.










Respiratory related evoked potentials (RREP) were generated by storing 500

msec electroencephalogram (EEG) activity using a data acquisition system

(Cambridge Electronic Design Limited, Model CED 1401). The digitalized sample

was stored on computer disc for subsequent analysis. The loads were presented

in blocks of 5 and delivered randomly using a changeover design to control for

confounding factors. Each load was presented a total of 80 times in 4

experimental trials. Sixty to 80 occlusions were averaged using a computer

averaging program (SIGAVG, Cambridge Electronic Design Limited). The control

breaths were also averaged and subsequently subtracted from the averaged

resistive load responses to remove artifacts. The peak P1 amplitude was

measured in volts.

The third experiment followed a protocol similar to that of the

second experiment. In addition to recording the RREP (grounded to the

right ear) and Pm, the esophageal pressure (Pes), gastric pressure (Pga),

transdiaphragmatic pressure (Pdi), which were measured in cmH20, and ME were

also recorded. Thirteen men and 2 women, who were experienced divers with no

history of pulmonary disease, participated in this study. The average age was 36

years. The test apparatus is represented in figure 1.

Two thin-walled latex balloons (length of 10 cm, and a diameter of 3.5 cm)

placed over a polyethylene catheter (i.d., 0.14 cm; o.d. 0.19 cm) were connected

to differential pressure transducers (Micro Switch 14PC), which were calibrated

with a water manometer. A topical anaesthetic (Citacaine 2%) was applied to the





Response Meter

Figure 3-1 Test apparatus used in the third study.


oropharynx before each experiment to reduce the gag reflex, and the balloon was

lubricated with 2% viscous xylocaine. Pg, was measured by advancing a balloon

transnasally down the esophagus until there was a sharp rise in pressure during

a sniff indicating the balloon entered the stomach (Wanke, Schenz, Zwick, Popp,

Ritschka, & Flicker, 1990). The gastric balloon was filled with the appropriate

amount of air for the balloon to prevent its collapse. Pes was measured with an

identical latex balloon placed in the middle third of the esophagus. During

calibration, Pg, and Pes sensitivities were adjusted to zero and Pdi was








23

determined electronically by the difference between Pga and Pes pressures (Milic-

Emili, Mead, Turner, & Glauser, 1964; Agostoni, Sant'Ambrogio, Del Portillo

Carrasco, 1960).

Resistive loads and control breaths were presented using the same protocol

for the presentations as performed in the second experiment. Along with the

RREPs, Pg,, Pes' Pdi, and Pm were recorded with the data acquisition system.

After presentation of each block of 5, the subject indicated their ME for the load

using a hand-held meter with a modified Borg scale (Borg, 1982).




Analysis


For the first study, an analysis of variance (ANOVA) compared the

differences between the ME for the different presentations and resistive loads. A

paired t-test was used to detect the differences in the reported ME for each load

presented at the onset of inspiration and at midinspiration. A linear regression was

performed on the log-transformed data. The relationship of ME to R was plotted

on a log-log graph.

In the second study, after the ANOVA detected differences in the P1

amplitude for the R, a paired t-test was performed.

In the third study, the magnitudes of Pdi, Pdi slope, Pm' es,, and Pg, were

referenced to the peak P1 amplitude. The slope was determined for the linear










portion of the Pdi wave at the onset of the load. Pdi, Pdi slope, Pm= es,, and Pga
are the differences between the control breath and the loaded breath.

An ANOVA compared the differences of the RREP peak P1 amplitude

(uvolts), Pdi (cmH20), the slope of Pdi (cmH20/sec), Pm (cmH20), and Pes

(cmH20), and Pga (cmH20) obtained at the three resistances (cmH20/L/sec).
Where significant differences were found, a paired t-test was performed to

determine differences within the groups of response variables and R.

After a log10 transformation of the group averaged data, a correlation

matrix between resistance, Pi amplitude, Pdi, Pdi slope, Pm, and Pes was

produced using the Pearson Correlation Coefficient. The various relationships

were plotted on a log-log graph, and a linear regression performed.

ME was analyzed against resistance using the Friedman two-way ANOVA.

When significant differences were found, a Wilcoxon matched-pairs signed rank

test was performed. This test was used to test for significant differences in P1

amplitudes, Pdi, Pdi slope, Pm, and Pes and ME. A correlation matrix was

produced with a Spearman rank correlation coefficient. The relationships were

graphed on a log-log plot, and a linear regression performed on the log-

transformed data.

A significance level of a=.05 was set for the analyses in all experiments.














RESULTS AND DISCUSSION


Results


Study 1

Progressive increases in the magnitude of inspiratory resistive loads resulted

in an increase in the perceived magnitude of the load regardless of the timing of

the presentation. The subjects generally estimated the midinspiratory

presentations to be of lessor absolute magnitude than those presented at the

onset of the breath. A paired t-test found significant differences for the

intermediate loads of 5, 9, and 13 cmH20/L/sec (p <.015). The group averaged

data is shown in table 4-1.



Table 4-1 Group averaged ME for inspiratory resistive loads (n= 9).

Resistance (cmH20/L/sec)
2 5 9 13 21
Onset 1.39 3.70 5.59 6.45 7.43
& SEM 0.34 0.66 0.79 0.80 0.77


Midinspiratory 1.18 2.46 4.13 4.85 5.82
& SEM 0.30 0.48 0.70 0.80 0.85








26

A log-log plot of the group averaged ME for each condition showed a linear

relationship between the load magnitude and the load perception for both types

of presentations, figure 4-1. The group averaged response to the resistive loads

becomes curvilinear at the higher loads. No significant differences were found

between the slopes of the linear regression of the log-transformed data obtained

for the two presentations. These relationships are described by the following

equations:

onset ME = -0.0482 + 0.7500 R (R2= 0.9409)

midinspiratory ME = -0.1791 + 0.7532 R (R2=0.9718)



Study 2

The RREP P1 peak amplitude occurs within 50 to 60 msec of the

interruption. The group mean P1 amplitude increased significantly with the

increase in the resistive load, table 4-2. The RREP from one subject is illustrated

in figure 4-2.



Table 4-2 Group averaged P1 amplitude (rt SEM) for inspiratory resistive
loads (n =6).

Resistance CzC 4Cz-C4 P1

(cmH20/L/sec) (pvolts) voltst)
2 1.58 & 0.58 1.36 &t 0.27
9 2.51 & 0.50 2.43 & 0.58
21 3.66 & 0.67 3.09 & 0.46











Onset
Midinspiratory















10 104
Resistance (crnH20/L/sec)

Figure 1 Effect of timing of the inspiratory interruption on the magnitude estimation
of the resistive load (group average +t SEM, n= 9).


The log-log plot of the group averaged P1 amplitudes against resistance

demonstrated a linear relationship represented in figure 4-3. The regression of the

group averaged log-transformed data is described by the following equations:

Cz-C3 P1 = 0.0855 + 0.3514 (R2 = 0.9895)

Cz-C4 P1 = 0.0312 + 0.3545 (R2 = 0.9945)



Study 3

In the third experiment, only 10 subjects were used in the analyses.

Subjects were excluded if any response variable was not interpretable. The













O er w
6o

$--' a
E

rd"i 0g


X1 I 'P
O er we

ds
O c




" a ~ q I




C1.L





o I t I















Cz-C4













10 100

Resistance (emH20/L/sec)

Figure 4-3 Group averaged P1 amplitude (t SEM) in response to an inspiratory
resistive load (n =6).


following criteria was used for exclusion: when the Pdi was negative, it was

assumed to reflect an inappropriate Pes due to an esophageal peristaltic

contraction; a wandering EEG baseline that made it difficult to assess the peak P1

amplitude without bias. Subject data is presented in the appendix.

The RREP P1 amplitudes, Pm, Pes' Pdi, Pdi slope, and ME significantly

increased with the increase in the inspiratory resistive load. The resultant changes

in the RREP, Pdi, Pes, and Pm within one subject are illustrated in figure 4-4.

There were significant differences between the reported ME for the recorded

levels of P1 amplitudes, Pm, Pes' Pdi, and Pdi slope. There were no significant


















L.



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33

changes in Pga for the different resistive loads. The log-log plot of the group

averaged Pdi, es,, and Pm against the resistive load demonstrated linear

relationships, figure 4-5. The relationship of the log-transformed data can be

described by the following equations:

Pm = -0.1212 + 0.2690 R (R2 = 0.9946)

Pes = -0.6254 + 0.2043 R (R2 = 0.9996)

Pdi = -0.7559 + 0.2271 R (R2 = 0.9996)


Pmi


Resistance (emH20/L/sec)

Figure 4-5 Group averaged Pdi, Pes, and Pm (+ SEM) in response to
inspiratory resistive loads (n =10).


There was no difference in the relationship between Pdi and Pdi slope to

resistance:








Pdi slope = 0.7648 + 0.2237 R (R2 = 0.9994) 34

The relationship of the group averaged P1 amplitudes to resistance is

illustrated in a log-log plot, figure 4-6. The linear relationships of the log-

transformed data can be described by the following equations:

Cz-C3 = 0.1304 + 0.3268 R (R2 = 0.9997)

Cz-C4 = 0.1461 + 0.2151 R (R2 = 0.9592)





















Resistance (cmH20/L/sec)
Figure 4-6 Group averaged P1 amplitude (+ SEM) in response to inspiratory
resistive loads (n = 10).


The subjects used in the third study were experienced divers. After the

experiment, a number of subjects stated that the loads experienced during this

protocol were much less than the ventilatory loads experienced during diving

operations. The log-log plot of the group averaged ME showed a linear





35

relationship to resistance, figure 4-7. The linear regression of the log-transformed

data is:

ME = 0.1389 + 0.4149 R (R2 = 0.9854)

There was a high correlation between all the response variables and R.


1 10 100

Resistance (cmH20/L/sec)

Figure 4-7 Group averaged magnitude estimation (+ SEM) of inspiratory
resistive loads (n =10).


The perceived magnitude of an added resistive load can be described by

Steven's power law. The slope of the linear regression equation of the log-

transformed data relates the psychological magnitude to the physical magnitude.

ME has a direct linear relationship with the P,, Pes, Pdi, I'di slope, and the P1

amplitudes. The relationships for Pm' es,, and Pdi is represented in figure 4-8.

























Pdi [Pas] Pm


0.1 1 10

Pressure (cmH20)
Figure 4-8 Group averaged Pm, Pes, and Pdi (a SEM) measured for the
magnitude estimation (a SEM) of the inspiratory resistive load (n= 10).


The linear regressions of the log-transformed data for those response variables are

described by the following equations:

ME = 0.3253 + 1.5478 Pm (R2 = 0.9977)

ME = 1.4107 + 2.0348 Pes (R2 = 0.9898)

ME = 1.5174 + 1.8224 Pdi (R2 = 0.9804)

There was no difference in the coefficient obtained for Pdi slope and Pdi as they

are related to the ME of the load: ME = -1.1841 + 1.8596 Pdi slope (R2 = 0.9908)

The ME of the load is linearly related to the P1 amplitudes and are illustrated

in figure 4-9. The linear relationships of the log-transformed data are described by








































0.1 1 10

P1 Amplitude (pvolts)

Figure 4-9 P1 amplitude (a SEM) measured for the magnitude estimation (a
SEM) of an inspiratory resistive load (n = 10).


This study demonstrated a linear relationship between the P1 amplitude and

Pm, figure 4-10. The following equations describe the linear relationship of the

group averaged log-transformed response variables of P1 amplitudes to Pm:

Cz-C3 P1 = 0.0177 + 1.2067 Pm (R2 = 0.9919)


the following equations:

ME = 0.3050 + 1.2667 Cz-C3 (R2 = 0.9801)

ME = -0.1014 + 1.8037 Cz-C4 (R2 = 0.9898)

There was a high correlation between ME and Pm' es, Pdi, Pdi slope, and the P1


amplitudes.


Cz-C4


Cz-C3





1 __


=0.2448 + 0.7833 Pm (R2 0.9254)


Cz-C4 P1


Cz-C4


1 10

Pm (cmH20)
of mouth pressure (a SEM) to the RREP P1 amplitude


Figure 4-10 Relationship
(at SEM), (n = 10).


The relationship of P, to the P1 amplitude is the result of the relationship

of Pm to the driving pressure of the respiratory apparatus. The relationship of the

log-transformed data found in this study was:

Pm = 0.7731 + 1.1827 Pdi (R2 = 0.9915)

Pdi is linearly related to the P1 amplitude. There were no real differences

between the coefficients for Pdi and Pdi slope. The log-transformed data

demonstrated linear relationships which can be described by the following

equations:









































Cz-C3 P1 = 0.9574 + 1.4392 Pdi (R2 = 0.9999)

Cz-C4 P1 = 0.8641 + 0.9508 Pdi (R2 = 0.9665)

Cz-C3 P1 = -1.2463 + 1.4595 Pdi slope (R2 = 0.9982)

Cz-C4 P1 = -0.5841 + 0.9561 Pdi slope (R2 = 0.9486)

The log-log graph of Pdi versus the P1 amplitudes is shown in figure 4-11.


czr-c4

Cz-C3


Pdi (cmH20)
Figure 4-11 Relationship of the transdiaphragmatic pressure
RREP P1 amplitude (a SEM), (n= 10).


(aI SEM) to the


The relationships of the log-transformed Pdi, Pes, and Pm to the RREP P1

amplitude are similar and can be described as follows:

Cz-C3 P1 = 0.9574 + 1.4392 Pdi (R2 = 0.9999)

Cz-C3 P1 = 0.8692 + 1.5981 Pes (R2 = 0.9986)










Cz-C3 P1 = 0.0177 + 0.2067 Pm (R2 = 0.9919)

Cz-C4 P1 = 0.8641 + 0.9508 Pdi (R2 = 0.9665)

Cz-C4 P1 = 0.8023 + 1.0480 Pes (R2 = 0.9509)

Cz-C4 P1 = 0.2448 + 0.7833 Pm (R2 = 0.9254)




Discussion




Summary Statement

The results of these studies demonstrated a direct linear relationship

between the perceived magnitude of an inspiratory resistive load and cortical

neural activity, the RREP, and the transdiaphragmatic pressure.



Relationship, Between Load Application Timing and Magnitude Estimation

Resistive load detection occurs early during an inspiration, and the temporal

pattern of pressure development plays a major role in load discrimination

(Zechman et al., 1981). Thus the subject is more sensitive to the resistive load

presented at the beginning of inspiration and, therefore, the perceived magnitude

of the resistance was greater when the load was presented at the onset of

inspiration.

The differences in the absolute ME reported between the two presentations

may be due to an interaction with volume during a midinspiratory load. Elastic










loads are detected later during an inspiration when volume information is the

greatest (Campbell et al., 1963; Zechman et al., 1981). Perception of a resistance

is flow dependent, and peak flow occurs near the middle of a breath (Zechman et

al., 1981, Burki, 1981). Hence, the subject has a reduced awareness of a resistive

load during midinspiration where flow information is maximal yet inflation has

occurred .

Steven's power law describes the relationship of the perceived psychological

magnitude to the physical magnitude of the stimulus (Stevens, 1970). Resistive

loads presented at the onset of inspiration have a linear relationship with a power

function of 0.75. This power function is consistent with the power function of 0.80

for the reported ME in young adults for inspiratory resistive loads that ranged

between 1.2 to 50 cmH20/L/sec (Killian et al., 1981). The power function in the

third study was 0.41, which is consistent with previous studies on older individuals

and patients with obstructive airway disease (Harver & Mahler, 1990). Though the

subjects had no evidence of pulmonary disease, their exposure to continuous

ventilatory loads as divers may have altered their perception of breathing loads.

The power function describing the increase in sensation to the

midinspiratory resistive load was 0.7532. This power function is the same as that

observed for the ME of a resistive load presented at the onset of inspiration. This

suggests that similar sensory modalities are utilized regardless of the timing of the

presentation. Therefore, precise timing of an interruption is not necessary for

evaluating the neurological events associated with load perception.








42

The results of the first study suggest that the sensitivity of detecting resistive

loads is the same whether the resistance is applied at the onset of inspiration or

at midinspiration. However, intermediate resistances applied at midinspiration are

perceived to be of lessor magnitude than when the same load is presented at the

onset of the breath.



RREP and Resistive Loads

The second study, using midinspiratory occlusions, demonstrated that the

RREP P1 amplitudes increased as the resistive load increased. The characteristics

of the respiratory related evoked potentials are similar to other somatosensory

evoked potentials (Davenport et al., 1986). The P1 wave of an evoked potential

is believed to represent the initial activation of the somatosensory cortex by a

stimulus (Desmedt et al., 1983), and the P1 amplitude is related to the magnitude

of the stimulation by a power function (Franzen & Offenloch, 1969). In the case

of the RREP, the subject generates the stimulus by inspiring against a restricted

airway. The magnitude of the resistive load encountered is directly related to the

peak P1 amplitude.

In the third experiment, the change in the P1 amplitude in response to a

resistive load was different between the cerebral hemispheres. These results are

in contrast to the results found in the second experiment. The apparent difference

probably represents a range of values (0.2 to 0.35) that can be used to describe

the relationship of the P1 amplitude to R, which became evident with the larger







43
sample size used in the third experiment. Figure 4-12 represents the progressive
increase in the P1 amplitude in one subject in response to an increase in
resistance.


Control


Cz -C3


C C4


] 2 uv


2 cmH201Llsec

-i-~~J--- ] 2 uv rJ"
P1 1?
9 cmH20Llsec

12/-CL~~ ] 2 uv i"-
P1
21 cmH201Llsec

~-,T 2 uv ~/~-
P P1
Figure 4-12 One subject's signal averaged RREP in response to inspiratory
resistive loads. The control breath was subtracted from the loaded breath.


Revelette and Davenport (1990) reported that a midinspiratory occlusion

resulted in a larger RREP and P1 amplitude. However, the subjects perceived the
load presented at the onset of a breath to be greater than the load presented at
midinspiration. The interaction between tidal volume and flow may result in
additional afferent information which may contribute to the larger RREP recorded










during a midinspiratory occlusion.

The results of the second and third study further suggests that the RREP

is a cortical evoked potential that have similar characteristics in response to varying

degrees of stimulation. The source of the afferent information responsible for

eliciting the RREP probably arise from the respiratory muscle afferents (Eisele et

al., 1968; Stubbing et al, 1981; Zechman et al., 1985).



RREP. Pd,: and Magnitude Estimation

The third experiment demonstrated the relationship of the RREP to the

respiratory apparatus and its ability to generate a driving pressure. The specific

afferents that are stimulated during an inspiratory interruption are unknown.

However, afferents from the mouth, chest wall, and the diaphragm can facilitate the

perception of a respiratory load (Bennett et al., 1961; Burki, et al., 1983; Campbell

et al., 1961; Chaudhary & Burki, 1978; Davis, 1967; Eisele et al, 1968; Guz et al.,

1966; Taguchi, Kikuchi, Hida, Iwase, Satoh, Chonan, & Takishima, 1991; Paintal,

1977).

Mechanoreceptors in the mouth and pharynx may be activated by rapid

changes in Pm and may contribute to the RREP.

Despite the relationship, the afferents stimulated with mouth pressure may

not contribute to the RREP. Davenport, Holt, and Hill (1990) reported that the

increases in mouth pressure as a result of CO2 stimulation did not increase the

magnitude of the P1 amplitude during an inspiratory occlusion. In addition, they










reported large disparities between the P1 latency of the RREP and that P1 latency

of tactile stimulation to the face or tongue. They concluded that the afferents in

the mouth and pharynx may not mediate the RREP.

During quiet breathing, Pdi is the sum of the decrease in Pes, which reflects

pleural pressure, and any increase in Pg, that may have occurred. Grimby et al.

(1976) suggested that the diaphragm works in concert with the rib cage muscles

such that any change in Pdi is equal to the changes in the chest wall pressures

and pleural pressures. Hence, Pdi also reflects the driving pressure of the chest
wall.

Pdi is the best measure of the force produced by the contraction of the

diaphragm (Moxham, Morris, Spiro, Edwards, & Green, 1981). There is a close

relationship between Pdi and Pes, and the proportion of Pdi attributable to Pes can

vary depending upon the breathing pattern of the individual (Field et al., 1984).

This study found similar responses of Pdi and Pes to the resistive loads because

there was no significant change in Pga-

Several factors can affect the measurement of Pdi. The position of the

relaxed diaphragm, and thus its position on its length-tension curve, depends upon

the subject's lung volume (Agostoni & Rahn, 1960; Road & Leevers, 1988). This

factor did not influence the measurements in this experiment because all the

subjects were at rest and breathing at their functional residual capacity.

Furthermore, there can be a strong recruitment of accessory muscles during

forceful inspiratory maneuvers resulting in a low Pdi (DeTroyer & Estenne, 1981).










Because the resistive loads were presented only momentarily, it is doubtful that the

Pdi measurement was significantly affected. The P1 amplitude response appears
to be closely associated to Pdi. However, further studies are necessary before a

causal relationship can be ascribed.

The perceived magnitude of added breathing loads is directly related to the

inspiratory muscle force and indirectly related to the added load (Killian et al.,

1982). Specifically, the rate and temporal pattern of Pdi augmentation precedes

load detection and increases in response to graded elastic or resistive inspiratory

loads (Zechman et al., 1985). This experiment documented an increase in Pdi and

its rate of change in response to a resistive load. Thus sensing load induced

changes in Pdi may play a role in inspiratory load detection.

The similarities in the power function for Pdi and Pes is not surprising since

they are directly related to each other in this experiment. Pm is related to the P1

amplitude because mouth pressure is a function of the respiratory system's driving

pressure. The difference between Pm and Pdi or Pes is due to the amount of
mouth stimulation that occurred while inspiring against a load.

The RREP P1 amplitude is linearly related to the driving pressure of the

respiratory apparatus and is correlated to the ME of the resistive load. Previous

studies strongly suggested that detection in diaphragmatic tension, as reflected by

pressure changes within the respiratory system, contributes to respiratory

sensation (Bakers & Tenney, 1970; Zechman et al., 1985). This study found that

the psychophysical and neurophysical events are described by the same power










function suggesting a basic relationship between Pdi, the RREP P1 amplitude, and

the ME of the resistive load. Though the principal afferents responsible for the

RREP are not known, they probably are associated with the diaphragm and chest

wall. Further studies using selective nerve blocks are necessary to delineate the

role of the various afferents that combine to form the P1 amplitude.



Model for Behavorial Compensation to a Respiratory Load

Pressure as a function of volume provides information on load perception

(Fogarty et al., 1978), and the ability to sense volume requires information about

muscular tension (Wolkove et al., 1981). The monitoring of pressure and volume

changes can be performed by the mechanoreceptors affected by muscular

contraction (Stubbing et al., 1981). Specifically, these afferents monitor the

changes in the Pdi, which predominate over the force generated by all the

inspiratory muscles, and implies that the sensing Pdi is important in load

compensation (Lopata et al., 1983). Pdi can be sensed by receptors located in the

diaphragm (Burki et al., 1983; Holt et al., 1991), and any change in Pdi that elicits

a sensation can be related to the behavioral compensation for the load (Zechman

et al., 1985).

Within the phrenic nerve are the respiratory related efferents from the

diaphragm. These fibers project to the somatosensory cortex (Davenport et al.,

1985). By using scalp electrodes, a RREP can be recorded in response to an

inspiratory interruption in the sensory cortex region referenced by Cz-C3 and Cz-










C4 (Davenport et al., 1986). The P1 amplitude may represent the early cognitive

potential which is related to the stimulus intensity.

The RREP found in humans may represent the summation of many afferents

related to the respiratory apparatus. An occlusion occurring at the onset of

inspiration produces a larger RREP P1 amplitude than the resultant peak from a

midinspiratory occlusion (Revelette & Davenport, 1990). However, the subjects

perceived the load presented at the onset of a breath to be greater than the load

presented at midinspiration. This suggests the interaction between tidal volume

and the perceived magnitude of the load. The additional afferent information may

attribute to the larger RREP recorded though the same neurophysical mechanism

is responsible for the evoked potential.

With the presentation of graded midinspiratory interruptions, a series of

events were recorded. There was an increase in the Pdi magnitude and its rate

of change (Pdi slope). These responses were linearly related and strongly

correlated with the increase in the RREP's P1 amplitudes. This pattern is the same

as other cortical evoked potentials in response to increases in stimulus intensity

(Franzen & Offenloch, 1969). The peak amplitudes in turn were strongly correlated

to the perception of the load.

Mechanoreceptors associated with the respiratory muscles synapse in the

somatosensory cortex. They are stimulated by ventilation and increase their output

magnitude with increasing resistive loads. Processing of that afferent input results

in the ME of the load. An overview of the neural path for behavioal load










compensation is illustrated in figure 4-13.




MECHANO- SOMATOSENSORY MOTOR MAGNITUDE
RECE TOR OERE OTX AWRNS ETMTO




RESPIRATORYRESPIRATORY L&l FLOW CAIA
AMU SCL MUSCLES Av VOLUME LOAD



Figure 4-13 Neural path for the behavorial compensation to respiratory loads.


Exactly how the information is processed within the cortex is unknown.

Steven's power function suggests that the low power function that describes the

P1 amplitudes and Pdi to R implies a mechanism of nonlinearity to allow sensing

of a wide range of input and the processing capacity of the central nervous

system. The power functions greater than 1, P1 amplitude and Pdi to ME,

suggests an expander function (Stevens, 1970).

Exactly what information, the absolute magnitude of Pdi or Pdi slope, is

processed is unknown. The amount of diaphragmatic tension generated over time

reflects the oxygen cost of ventilation (Field et al., 1984), and the temporal

patterning of afferent information is important in load discrimination (Zechman &

Davenport, 1978). In this study, the relationship of Pdi and Pdi slope to load

perception was the same. Therefore, perceiving the rate of change in Pdi may










factor in the ME of a load in addition to the amount of force generated.

When a ventilatory load is added to the respiratory apparatus, there is a

resultant change in flow and volume produced by the muscles. The alterations in

tension, reflected by pressure, the rate of pressure change, Pdi slope, which may

be related to flow, and volume are detected by the respiratory muscles' afferents,

particularly the diaphragmatic mechanoreceptors. These afferents project to the

somatosensory cortex which result in a motor response to the load, as well as the

perception of the load. The magnitude of the efferent response may also

contribute to the awareness of the ventilatory load.

Behavorial load compensation relies upon the sensory information from the

respiratory apparatus. The diaphragm's afferents synapse within the

somatosensory cortex and respond in the same manner as other sensory

modality's evoked potential. Cortical mapping studies are necessary to determine

what part of the cortex is then stimulated to produce a ventilatory response and

perception of the load.













SUMMARY AND CONCLUSIONS


Summary


Humans can perceive and estimate the magnitude of ventilatory loads by

mechanisms not clearly understood. Pdi represents the driving pressure of the

lungs and chest wall, and as inspiratory resistance increases, Pdi increases in

response to the load. A respiratory related evoked potential can be recorded over

the somatosensory cortex, and its P1 amplitude increases with increases in a

resistive load. There is a direct linear relationship between Pdi and the P1

amplitude, which in turn is directly related to the magnitude estimation of the load.

In conclusion, the magnitude of the respiratory load sensation is related to the

transdiaphragmatic pressure and the P1 amplitude of the respiratory related

evoked potential.


Conclusions




1. The magnitude estimation of inspiratory resistive loads have the same slope

on a log-log relationship for both onset and midinspiratory presentations, which








52

indicates that the time of the load presentation does not affect the subject's

sensitivity to the load.

2. Subjects generally estimated the midinspiratory loads to be of lessor

absolute magnitude than loads presented at the onset of the breath. This

suggests an interaction between the tidal volume and the perceived magnitude of

the load.

3. There was a direct linear relationship between the magnitude of inspiratory

resistance and the RREP P1 amplitude.

4. Transdiaphragmatic pressure and its slope is directly related to the P1

amplitude which in turn is correlated to the perception of the ventilatory load.














APPENDIX
SUBJECT DATA IN RESPONSE TO A RESISTIVE LOAD



2 cmH20/L/sec


Subject Cz-C3 Cz-C4 Pdi Slope Pm Pes Pga ME
1 1.494 2.329 0.111 4.979 0.693 -0.190 0.058 1.27
2 0.429 1.445 0.115 6.212 0.665 -0.258 0.124 2.30
3 1.535 1.477 0.178 10.736 0.699 -0.321 0.094 0.48
4 1.711 1.348 0.187 5.152 0.812 -0.222 0.058 2.68
5 1.391 3.050 0.306 7.840 0.943 -0.359 0.085 2.78
6 0.729 1.119 0.214 6.784 0.595 -0.308 0.079 1.22
7 0.249 1.658 0.261 6.050 0.940 -0.289 0.015 1.55
8 0.548 1.089 0.222 6.629 1.242 -0.266 0.075 0.81
9 0.571 1.714 0.316 9.591 1.172 -0.354 0.057 1.23
10 0.656 1.377 0.149 3.777 1.267 -0.159 0.035 3.59
Mean 0.931 1.661 0.206 6.775 0.903 -0. 272 0.062 1.79
& S.D. 0.539 0.602 0.073 2.120 0.251 0.067 0.031 0.99















Subject Cz-C3 Cz-C4 Pdi Slope Pm Pes Pga ME
1 2.430 3.879 0.197 8.806 1.099 -0.231 0.024 4.62

2 0.911 1.791 0.142 9.657 1.077 -0.320 0.144 2.88

3 2.332 2.321 0.313 11.910 1.044 -0.436 0.106 0.97
4 2.022 1.547 0.271 10.726 0.998 -0.338 0.090 5.47

5 1.695 3.149 0.494 13.225 1.334 -0.535 0.080 6.70

6 0.897 1.532 0. 275 7.213 1.028 -0.371 0.103 2.19
7 2.475 1.727 0.321 6.347 1.541 -0.342 0.019 3.05

8 0.679 1.529 0.294 8.166 1.920 -0.415 0.179 1.81

9 0.759 1.801 0.402 15.640 1.599 -0.472 0.117 2.73
10 0.872 1.867 0.164 4.146 2.393 -0.275 0.123 6.28

Mean 1.507 2.114 0.287 9.583 1.403 -0.373 0.098 3.67
-5 S.D. 0.756 0.792 0.107 3.415 0.464 0.092 0.049 1.97


9 cmH20/L/sec















Subject Cz-C3 Cz-C4 Pdi Slope Pm Pes Pga ME
1 3.240 4.857 0.279 9.164 1.181 -0.282 0.002 5.69

2 1.320 2.182 0.161 10.237 1.358 -0.338 0.162 2.81

3 2.705 3.224 0.345 15.264 1.144 -0.438 0.108 1.36

4 2.500 2.102 0.327 11.337 1.169 -0.473 0.121 8.14

5 2.314 3.080 0.559 14.626 1.511 -0.641 0.116 7.00

6 1.230 2.846 0.299 7.494 1.187 -0.453 0.133 3.13

7 3.302 2.832 0.354 10.715 1.718 -0.482 0.024 3.97

8 0.722 2.460 0.253 8.550 2.417 -0.327 0.137 2.52

9 1.300 1.875 0.557 18.392 2.133 -0.554 0.156 3.83

10 1.493 2.546 0.382 8.608 3.049 -0.410 0.066 8.16

Mean 2.013 2.800 0.352 11.439 1.687 -0.440 0.103 4.66

+ S.D. 0.914 0.834 0.125 3.531 0.649 0.108 0.055 2.43


21 cmH20/L/sec














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BIOGRAPHICAL SKETCH


I graduated from Gannon University, Erie, PA, in 1974 with a B.S in biology,

and Temple University School of Medicine, Philadelphia, PA, in 1980 with an M.D.

I was commissioned as an active duty naval officer upon graduation from medical

school. The first year of my graduate medical education in family practice was

performed at the Naval Hospital, Pensacola, FL. My subsequent training was in

undersea medicine, which involved the practice of general and diving medicine.

I am a member of the Underwater and Hyperbaric Medical Society and am

licensed to practice medicine in Pennsylvania and Florida. Prior to attendance at

the University of Florida, I was stationed at the Navy Experimental Diving Unit

(NEDU), Panama City, FL, and my duties involved the design and testing of

underwater breathing apparatus and their effect on the diver's breathing and work

performance. I will be returning to NEDU as the assistant senior medical officer

upon completion of my studies.








I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of D ctor of Philosophy.



JaeE. Graves, Chair
Assistant Professor of Exercise and
Sport Sciences

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.



Paul W. Davenport
Associate Professor of Physiology

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.



Scott K. Powers
Professor of Exercise and Sport Sciences

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doct ~f Philosophy.



Michael Pollock
Professor of Exercise and Sports Sciences

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.



teDodd
Associate Professor of Exercise and
Sport Sciences








I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of D ctor of Philosophy.



JameS E. Graves, Chair
Assistant Professor of Exercise and
Sport Sciences

I certify that I have read this study and th-at in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.



Paul W. Davenport
Associate Professor of Physiology

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.



Scott K. Powers
Professor of Exercise and Sport Sciences

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doct ~f Philosophy.



Michael Pollock
Professor of Exercise and Sports Sciences

I certify that I have read this study and that in my opinion it conforms to
acceptable standards of scholarly presentation and is fully adequate, in scope and
quality, as a dissertation for the degree of Doctor of Philosophy.


Steplyth Dodd
Associate Professor of Exercise and
Sport Sciences









This dissertation was submitted to the Graduate Faculty of teCollege of
Health and Human Performance and to the Graddat ho and accepted
as partial fulfillment of the requirements for the g ofD r*fPilosophy.

August 1992
De~an, Coll ge of
Health and Human Performance



Dean, Graduate School




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