Proceedings of the 22"dAnnual EMBS International Conference, July 23-28,2000, Chicago IL.
A comparative study of respiratory models
in control of ventilation
M.A. Maiianas', S.Romero' and P. Caminal'
Abstract - The aim of this work is to evaluate responses
and characteristics of three respiratory models (RSZ, RS2
and RS3) in the presence of the following stimuli: exercise,
hypercapnia and hypoxia. A comparative study among the
three closed-loop systems is performed in simulation: R S Z
has a controller to minimize the mechanical and chemical
work rate of breathing. RS2 and RS3 fit better to
physiological system with peripheral and central
components. The steady state response is evaluated at
different levels of stimulus by means of the variables:
ventilation, PaC0, and PaO,. In general, the stimulus and
variable that produces more differences among models are
exercise and ventilation, respectively. The best model to
indicate the homeostasis during the exercise is RSZ but it is
not possible to analyze hypoxia because there is no
feedback of PaOz. In the transient response, a settling time
of several seconds is found in RSI and a more realistic
value around some minutes is obtained in the other
models. Besides, whereas there are no overshoots in the
responses of RSl, they appear in P a 0 2 with RS2 and RS3
models because an exponential feedback of P a 0 2 is
considered. The influence of these time constants and
gains on the transient response is analyzed to obtain the
maximum values to keep the system stable. Finally, the
sensitivity of the system response with the dead space is
studied during exercise.
Keywords - Respiratory model, simulation, steady state,
transient response.
I. INTRODUCTION
The respiratory control system has been traditionally
modeled as a closed-loop system that adjusts the rate of
alveolar ventilation almost exactly to the demands of the body
so that the arterial CO2 pressure, PaC02, and arterial 0 2 data. Peripheral and central chemoreceptor, neural activity and
pressure, PaOz, remain practically constant. It is called
homeostasis and occurs even during severe exercise or other
types of respiratory stress [l]. As any closed loop system, the
behavior of respiratory system is defined by the continuous
interaction of controller and peripheral processes that are
being controlled.
The first quantitative model of chemical control of
respiration was [2]. This mathematical model has changed,
from the classical steady state description of Gray, through the
dynamic models of unidirectional ventilation [3], until the
model where the respiratory cycle is included [4]. Most of
them assume that the system is structured in different
intermediate processes. Every approach in the model implies a
separate law of the multi-tasking controller. However, these
control laws must be related each other, because they are
regulated by the same neural network which composes the
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respiratory controller. Three of these models have been chosen
to be studied in this work because of the variety in modeling
and control law [5][6][7]. Besides, they are complete
respiratory models and there is an exhaustive analysis of
chemical approach of respiratory control, i.e., the main
objective for these models is keep appropriate levels of
concentration of 0 2 and CO2 in the human body.
The respiratory system is non-linear, multivariable, with a
feedback dynamics and a delay that is permanently disturbed
by different physiological and pathological conditions. Control
of ventilation is automatic and normally involuntary in the
presence of different stimuli: from a change in metabolic
activity until a modification of external environment. Different
situations in control of ventilation are evaluated in this work:
moderate exercise, hypercapnia and hypoxia. The static and
dynamic ventilatory responses have been investigated by
means of simulation. The software used in this work is
Simulink v2.1 from MATLAB 5.1.O on PCWIN.
11. METHODS
ZLA Respiratory Models
The first analyzed model is [5] with chemical and neuro-
mechanical feedback. The expired ventilation, VE, proceeds
from an optimization approach to minimize chemical and
mechanical works in ventilation maintaining the homeostasis.
Its block diagram presents three important parts: chemical
plant (gas exchange process) and two blocks related to
chemical (chemoreceptor) and mechanical feedback and an
optimal controller. Although it is a static model, the chemical
plant is changed by the dynamic equations that appear in [XI.
The second model corresponds to [6] whose block diagram
fits better to physiological system with peripheral and central
components because all the parts proceed to experimental
respiratory muscle driving pressure are integrated in the
peripheral and central controllers whose mission is the
homeostasis.
The last model [7] is an extension of the second one. It
presents the same chemical plant but the chemoreceptors do
not act as controllers but perform their real physiological
function: get the PaC02 and Pa02 and send this information to
the controller located in the encephalic branch. The model
adds very important variables in the respiratory pattem
generation as tidal volume and constant inspiration and
'Department of Automatic Control
Biomedical Engineering Research Center (CREB)
Technical University of Catalonia (UPC)
Pau Gargallo 5,08028 Barcelona, Spain.
manYanas@creb.uoc.es
1601
 Proceedings of the 22ndAnnual EMBS International Conference, July 23-28,2000, Chicago IL.

expiration periods that determine the respiratory frequency. stimulus or situation is shown in Table 1 by means of the
In the chemical plant of last two models, there are more Percentile Root-mean-square Difference (PRD):
blocks and variables that indicate physiological processes than
the first one: gas concentrations in veins and arteries, gas
exchange in body tissue and brain, circulatory mixing and
circulation time from tissues to chemoreceptors. Comparing
the equations between [5] and [6][7], we can deduce the
following expressions: where x,(n) and x2(n) corresponds to the respiratory variable
from two models and N is the number of different levels of
simulated stimulus.

III.B Transient Response

where VCO, is whole-body metabolic CO2 production, VA is
The three dynamic models permit to evaluate the transient
alveolar ventilation, V, and V, are dead space ventilation and
response of the variables of interest in a selected situation of
volume, respectively, Vr is tidal volume, Q is cardiac output, exercise, hypercapnia or hypoxia. Whereas there are no
CvC02 and CaC02 are arterial and mixed venous blood CO2 overshoots in any response of model [5], they appear in Pa02
concentrations, respectively. in [6] and [7] because of the existence of an exponential
Furthermore, in the model [5] there is no feedback of Pa02 feedback of Pa02. Only in these lasit two models, Pa02 present
whereas in [6] and [7] it exists by means of peripheral a maximum overshoot around 300% with exercise.
chemoreceptor. Furthermore, a settling time (f50/0 of final value) of several
seconds is found in model [5] ancl a more realistic value of
II.B Stimuli some minutes is obtained in the other models. For example,
In this work, responses and characteristics of the three with a step from 0 % to 3% in PC02, the settling time for
respiratory models in the presence of the following stimuli are PaCO2 variable is 15 s, 525 s and 450 s in models [5], [6] and
evaluated moderate exercise, hypercapnia and hypoxia. [7], respectively.
In strenuous exercise, 0 2 consumption and CO2 production
can increase a lot. A value of $CO, 4 . 2 Vmin is considered at HI. C Influence of dead space volunie
rest until a maximum value of 1 Vmin with moderate exercise. Unfortunately, some of the air that a person breathes is not
V,ordinarily increases almost exactly in step with the useful for the gas exchange. The normal dead space volume in
increased level of metabolism to maintain the homeostasis. the adult is about 150 ml and this increases slightly with age.
Hypoxia can result from disturbances of respiration or a On occasion, however, some of the alveoli themselves are
reduction in the O2 pressure of inspired air, for example, partially functional because of albsent or poor blood flow
because of high altitudes. An input variable, P102, is through adjacent pulmonary capillaries. Therefore, this
considered to simulate hypoxia. In normal conditions volume that can reach 1 or 2 I is wasted and is called
P102=159 torr (21% of atmospheric pressure) and different physiological dead space. This (effect can be because of
levels of hypoxia until 98 torr (13%) are simulated. It is thrombosis of a pulmonary artery, excessive airway resistance
related with a decrease in Pa02. Hypoxia, if severe enough, to some alveoli (emphysema) and other conditions [ 11. So, it is
can cause death of the cells. In less severe degrees its results important to evaluate the sensitivity of this volume on pressure
are principally depressed mental activity and reduced work variables in the different models.
capacity of the muscles [13. In the simulations performed in [5], the V f l r ratio is
Hypercapnia corresponds to a presence of CO2 in the inhaled considered constant with a value of 0.2. However, the author
gas or CO2 retention. An input variable, PIC02, is considered comments that it declines with the exercise from a resting
from 0 torr (0% of atmospheric pressure) until 45 torr (6%). It value of 0.3 down to 0.1 at a VCO, =1 l/min. In-this work, the
means excess CO2 in the body fluids. When PaCO, rises above reduction is considered linearly. Model [6] considers a
60 or 75 torr dyspnea usually becomes very severe. The constant V, =2.28 Vmin and simulations in [7] use a constant
person becomes lethargic and sometimes even semicomatose value of VD=0.15 1 where VT is an internal variable of the
with levels from 80 to 100 torr. Anesthesia and death can model. In Figures 2 and 3, the sensitivity on expired
result when the PaCO2 rises to 100 or 150 torr [l]. ventilation and PaCO2 is shown and we can see the V f l ~
ratio in the Figure 4, all of them obtained in simulation at
111. RESULTS different levels of exercise in the three models.

III.A steady-state Response
In Figure 1, we can observe final values of variables of
interest (expired ventilation, PaC02 and Pa02) as a function of
different levels of exercise, hypoxia and hypercapnia.
Different colors are used to differentiate the steady-state
response among the three respiratory models. A mean value of
the differences between each couple of models with every
IILD Influence of time constants and controller gains
The presence of circulatory dlelays in gas transport and
controller gains in models [6] and [7], permit to analyze their
influence in the transient response. and stability of the system.
In general, when these time delays increase, the settling time
(ts) in respiratory variable of interest (expired volume, PaC02
and PaOz) remain around thesame valueuntilthis constant

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