EXPLORATORY STUDIES OF PHYSIOLOGICAL

COMPONENTS OF MOTION SICKNESS

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National Aeronautics and

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Ames Research Center

Moffett Field, California 94035

ARC275a (F«b81)
Enclosure III:

Project #2: Exploratory Studies of Physiological Components of

Motion Sickness

A Pilot Study of Cardiopulmonary Function Differences in

High and Low Motion Sickness Susceptibles.
PROGRESS REPORT

Project #2: Exploratory Studies of Physiological Components of Motion

Sickness: Cardiopulmonary Differences Between High and

Low Susceptibles.

Prepared by: Karen Naifeh, Ph.D./ Assoc. Professor, Pulmonary Physiology,

University of California at San Francisco.

Funding for this project was delayed, and only arrived in June. We

have therefore spent the last four months obtaining equipment and setting up

the project. The following is a report on a pilot study conducted in order to

evaluate new measures of dynamic cardiopulmonary function and begin to use

them to examine possible differences between high and low motion sickness

susceptible subjects. In a previous study (1) we demonstrated a strong

autonomic nervous system response to motion sickness, with significant changes

in heart rate (HR), finger pulse volume (FPV), which is a relative measure of

peripheral vascular resistance, respiratory rate (RR) and basal skin

resistance (BSR). The heart rate response was the strongest of these, and

differences in heart rate response emerged between susceptibility groups even

in the first two minutes of the motion sickness test. We therefore designed

the present project in order (l)to provide a more comprehensive examination of

cardiovascular autonomic response to motion sickness and (2) to determine

whether differences in cardiopulmonary function exist in high and low
PAGE 2

susceptible groups of subjects. This pilot study was performed in order to

develop new measurement techniques, test equipment for its ability to provide

accurately new measures of interest and to test the adequacy of these new

measures in differentiating between susceptibility groups.

In order to gain a more comprehensive view of dynamic cardiovascular

responses during motion sickness we have added the measures of stroke volume,

cardiac output, myocardial contractility, pre-systolic and systolic timing

intervals (all obtained by impedance cardiography); blood pressure; and total

peripheral resistance as calculated from cardiac output and blood pressure

measures. In order to assess the interaction of the respiratory and

cardiovascular systems we have added the measures of tidal volume, and rib

cage and abdominal compartmental volumes. We obtained all measures during

resting baseline conditions and during two different types of stressors which

are known to affect the cardiovascular system. These were the Valsalva

maneuver and mental arithmetic. In order to gain some notion as to whether

differences in these measures might be associated with differences in motion

sickness susceptibility, we studied subjects who had previously been

categorized as either high or low motion sickness susceptible in a standard

Coriolis (CSSI) motion sickness test.

METHODS

Subjects were six healthy males 35 to 55 years of age, three of whom

were high and three of whom were low motion sickness susceptibles.

The following impedance derived variables were obtained from a

Minnesota Impedance Cardiograph with associated microcomputer: stroke volune

(SV), cardiac index (CI) which is cardiac output adjusted for body surface
PAGE 3

area, cardiac contractility (CC), pre-ejection period (PEP) which is the

period of systole before the aortic valve opens, and ventricular ejection time

(VET) which is the period of systole during which the left ventricle is

actually ejecting blood into the aorta. For these measures, subjects were

fitted with four circumferential mylar tape bands, two around the neck and two

mid-chest; a microphone for monitoring heart sounds, and a precordial ECG. The

microcomputer automatically calculated all five impedance-related variables

for heart beats selected by the experimenter, and stored the data on cassette

tape. The microprocessor required a minimum of 8 seconds to calculate data

from each beat selected; another beat could not be selected until calculations

were completed. Blood pressure was recorded twice per minute from an automatic

cuff system (Narco Biosystems) worn on the left arm. Systolic and diastolic

pressures were derived from Karotkoff sounds picked up by microphone and

recorded, along with cuff pressure, on strip chart.

Respiratory tidal volume, and rib cage and abdominal compartmental

volumes were recorded using a Respitrace inductance plethysmography system

(Ambulatory Monitoring, Inc), calibrated by spirometry prior to each session.

A computer program for performing the calibrations, assessing the accuracy of

calibration and collecting the data was developed in this laboratory for the

project. Heart rate, respiratory rate, finger pulse volume, toe pulse volume

.and basal skin resistance were also measured as in previous studies in this

laboratory in order to compare the new measures with these older ones.

For the resting baseline session subjects sat in a reclining chair for

thirty minutes. One-minute means were computed for each variable for the

thirty minutes of the session. For the task session, a ten minute resting

baseline was recorded, following which subjects performed a Valsalva maneuver.
PAGE 4

For this, subjects held their breath in mid-inspiration, contracting abdominal

muscles against a closed glottis for 30 sec., then relaxed for a two minute

recovery period. A second Valsalva maneuver and recovery were then performed.

For the mental arithmetic condition subjects subtracted serial 17's from 500,

repeating each answer verbally, for a period of three minutes. Approximately

ten to twenty trials were carried out during the three-minute period,

depending on the mathmatical prowess of the subject. A mean for each

variable was calculated for each minute of the task session.

RESULTS

The impedance cardiography system and the Respitrace inductance

plethysmography system were found to be virtually incompatible when used

together. The frequency oscillator of the Respitrace system created large

artifacts in the impedance cardiography system which often could not be

eliminated. We did find that interrupting the mylar tape bands around the

chest so that they no longer formed a completely closed loop removed the

artifact in some individuals without degrading the impedance signal, but it

did not consistently allow us to obtain clean data from both systems. In those

instances in which it was impossible to obtain both impedance and respiratory

data, we chose to eliminate respiratory measurements. Since our N is small for

this pilot study, we did not analyze the respiratory data obtained from those

individuals whose data was artifact free. In order to overcome this

incompatibility problem we have decided to use the new piezo-electric strain

gauge system developed by this laboratory for the SL-3 flight to obtain the

pulmonary measures in our formal study. It measures pulmonary volumes using a
PAGE 5

different principle which is compatible with the impedance cardiography

system. Our software for obtaining respiratory data should require only minor

modifications in order to be used with the new transducers.

Our assessment of the impedance cardiography system is that it

provides relatively accurate data on a wide range of dynamic cardiovascular

variables and appears to be sensitive even to rapid changes in these

variables. It is therefore well suited to our purposes in the formal study.

The microprocessor designed to work with it we found to be largely unsuited to

our purposes. With the microprocessor one can obtain data from one heart beat

at a minimum of 8-sec. intervals. Thus much data is lost from the intervening

beats, especially when rapid changes in the cardiovascular system are

occurring. In the formal study, therefore, we shall tag time periods of

interst during experimental runs and obtain impedance data from all beats

of interest off-line from tape recorded data using our own software.

In spite of the above equipment limitations, valuable data were

gathered. Mean values for all variables across the resting baseline condition

for each subject are presented in Table 1. The values for all impedance

variables fall within accepted normal values as measured by classical

techniques (2).

Correlations were run between ANS variables for both the task and

baseline sessions in order to compare old and new measures of autonomic

function. Results are presented in Table 2. In general, the higher the

correlation between two measures having some relation to each other, the more

likely they are measuring identical phenomena. Thus although there is clearly

overlap, the relatively moderate correlations between old and new measures

indicates that we are measuring new aspects of autonomic function with the
PAGE 6

addition of these new variables. We were especially interested in how total

peripheral resistance (TPR), which takes into account all vascular beds,

compares with finger pulse volume (FPV), a very localized measure of relative

vascular resistance. Although relatively highly correlated under resting

conditions (r=-0.51), there is still a considerable amount of variance in TPR

which is not accounted for by FPV, and the correlation is much lower under

dynamic conditions (i.e., the presence of stressors). These latter measures

are of particular importance because vascular resistance is controlled solely

by the sympathetic arm of the ANS and may therefore be a means of dissecting

sympathetic and parasympathetic components of motion sickness. Cardiac

contractility, which is a measure of how forcefully the heart contracts

independently of ventricular filling, is also apparently solely under SNS

control. However, it is a cardiac measure, whereas peripheral resistance is a

vascular measure; the two may show differential effects depending on the

stimulus and the status of the cardiovascular system.

Next, possible differences between susceptibility groups were assessed

using analysis of variance. A three-way ANOVA (Epoch X Susceptibility X ANS

variable) was performed on the baseline data, where Epoch was each of three

consecutive ten-minute periods of the baseline session and Susceptibility was

"high" and "low". Results revealed no significant difference between

susceptibility groups on any measure, nor was there a significant change in

any variable across the session. It appears, therefore, that susceptibility

groups cannot be differentiated under resting conditions by any of the

physiologic variables we have measured.

A similar ANOVA (task X susceptibility X ANS variable) was performed

on data from the task session, where "task" was valsalva maneuver, valsalva
PAGE 7

recovery and math. There was a highly significant effect of Task (p<0.0001)

and of Susceptibility (p<0.003). Individual ANOVA's run susequently on each

separate variable revealed a significant effect of Task on stroke volume

(p<0.025), cardiac contractility (p<0.02), basal skin resistance (p<0.006)f

and finger pulse volume (p<0.025). There was a trend toward a significant

effect of Task on pre-ejection period and toe pulse volume (p<0.10). These

findings verify that the tasks administered did indeed produce changes in

dynamic cardiovascular function.

There was a significant effect of Susceptibility on stroke volume

(p<0.005) and cardiac contractility (p<0.05). Additionally, there was a

significant Task by Susceptibitlity interaction for stroke volume (p<0.007)

and BSR (p<0.01), and a trend toward significance for total peripheral

resistance (TPR) (p<0.08). Figures 1-5 present plots of all variables having

significant changes related to susceptibility.

As indicated by Figs. 1 and 2, two of the original measures, finger

pulse volume and BSR, were significantly different between susceptibility

groups. The difference in BSR appears to be attributable to the fact that the

low susceptibility group had a much higher resting BSR prior to the tasks than

did the high susceptibility group, possibly because they were more relaxed.

Paradoxically, heart rate, the measure snowing the strongest between group

difference in our original motion sickness study, was not different during

these non-motion sickness stressors. Three of our new cardiodynamic measures

did demonstrate differences, however. Although any conclusions we draw from

this small study must be very tentative, our findings may indicate that low

motion sickness susceptible subjects have a more flexible autonomic nervous

system, able to respond in either direction and return rapidly, whereas high
PAGE 8

suscptible subjects may not respond readily to more minor stressors, as the

ones in this pilot study certainly were, but respond more extremely to severe

stressors such as motion sickness itself. A larger study should help to

elucidate these issues. In summary, it appears that motion sickness

susceptibility groups can possibly be differentiated using simple, brief

stressors and measurments of cardiodynamic function. Further studies are

necessary to verify these findings; nevertheless, these results are

sufficiently promising to merit a formal study.

PROTOCOL FOR FORMAL STUDY

In the formal study, fifteen subjects previously determined to be high

and fifteen determined to be low motion sickness susceptible will participate.

They will undergo the following: two days of resting baseline, two sessions

with CSSI tests performed in the Rotating Room, and two sessions with

psychophysiologic stressors - Valsalva maneuver, cold pressor test, and 30

degree head-up tilt. We have decided to delete the mental arithmetic task

because mental arithmetic stress varies considerably across subjects and is

subject to movement artifact. Cold pressor has been added in its place.

Head-up tilt has been added as an additional pure physiologic stressor.

Measures taken during all sessions will be the old measures of HR, RR,

FPV, and BSR, plus the new measures of stroke volume, cardiac output, cardiac

contractility, systolic timing intervals, blood pressure, and transcutaneous

carbon dioxide tension (Pco2). Total peripheral resistance will be calculated

from blood pressure and cardiac output data. Estimates of rib cage and

abdominal compartmental volumes and tidal volume will be made from

piezo-electric strain gauges calibrated by spirometry. Pco2 will be included
PAGE 9

as a further monitor of ventilation, as ventilation and Pco2 are reciprocal as

long as metabolic rate is constant (3). Transcutaneous Pco2 has been shown to

accurately reflect arterial Pco2 in healthy subjects (4). Ihe transcutaneous

electrode heats the skin to 43 degrees C to provide arterialization of

capillary blood. Ihe output of the device is electronically adjusted to

reflect gas tensions at normal body temperature of 37 degrees C and to

compensate for skin metabolism of C02.

Our first priority will be to develop the software to obtain the

impedance cardiography measures and to make any modifications in our

respiratory volume software necessary to enable us to obtain volume data with

the piezo-electric strain gauge transducers. We will also attempt to modify

existing equipment to obtain EEC measures which, along with transcutaneous

Pco2, will provide information on Sopite Syndrome, the drowsiness and lethargy

often associated with motion sickness.
PAGE 10

REFERENCES

1. Cowings P, Suter S, Tbscano W, Kamiya J and Naifeh K. General autonomic

components of motion sickness. Psychophysiology (submitted).

2. Kubicek WG, Karnegis JN, Patterson RP, Witsoe DA, and Matson RH.

Development and evaluation of an impedance cardiac output system.

Aerospace Med 37:1208-1212, 1966.

3. Mitchell RA and Berger AJ. Neural regulation of respiration. Am Rev

Respir Pis vol.III, 1975, pp.206-224.

4. Hazinski TA and Severinghaus JW. Transcutaneous analysis of arterial

Pco2. Med Instrum 16:150, 1982.
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and new autonomic measures.

PEP

(sec)

FPV

TPV

HR

BSR

0

0

0

0

.60*

.21

.33*

.19

VET

(sec)

-0.73*

0.01

-0.66*

0.01

SV

(ml)

0.

-0.

0.

-0.

16

26

32*

44*

CI

(Vmin)

0.11

-0.51*

0.50*

-0.32*

CC SYS

(mmHg)

0.52*

0.27

0.37*

-0.14

0.01

0.24

0.02

0.29

DIAS TPR

(mmHg)

-0.

-0.

-0.

0.

42*

03

24

26

-0.51*

0.51*

-0.72*

0.11

*=significant at p<0.05

Table 3. Task session: Correlations between old and

new autonomic measures.

PEP

(sec)

FPV

TPV

HR

BSR

-0.

-0.

0.

0.

15

11

21

01

VET

(sec)

0.

0.

-0.

0.

02

23

37*

27

SV

(ml)

0.13

0.05

0.25

0.25

CI

(L/min)

0.22

-0.11

0.48*

0.04

CC SYS

(mmHg)

0.62*

0.29

0.41*

0.20

0

0

0

-0

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.38*

.15

DIAS

(mmHg)

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0.13

-0.12

-0.18

TPR

-0.20

0.21

-0.38*

-0.12

^significant at p<0.05
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