Robust Model-Based Estimators for Cardiac Nerve Activity

Cristian M. Radu Daniel T. Kaplan

Department of Physiology and Centre of Nonlinear Dynamics in Physiology and Medicine
McGill University, 3655 Drummond, Montreal H3G-1Y6, Quebec, Canada

Abstract
This paper outlines our design of a continuous esti-
mator for the sympathetic innervation of the heart. The
estimator is computed by linear methods, yet it is tested
on a nonlinear, detailed model of cardiovascular and res-
piratory dynamics. Inverting a model output (blood pres-
sure) to recover internal activity by means of the H1 and 20

structured singular value () design methods, allows di-

Power
10
rect treatment of signal and model uncertainty (noise and
nonlinearity, respectively), in a computationally conve- 0

nient, linear way. Numerical simulations suggest that the

1.4

variability of the blood pressure signal can be decoded to 1.2 0.5

yield good estimates of nerve activity despite parametric 1

0.4
uncertainty, in a range of physiological conditions. 0.8
0.3
1 Introduction 0.6
0.2
Interest in measures of the level of eerent cardiac
0.4

autonomic nerve activity is relatively old, and is justi- 0.2 0.1

HR FREQUENCY
RESP FREQUENCY
ed by studies correlating such levels with the patho-
physiological state of the organism [1]. Sympathetic and
vagal nerves mediate the re
ection of respiratory period- Figure 1: Spectral power of heart rate plotted as a function
icities in blood pressure (BP) and heart rate (HR), signals
which are thus thought of as noninvasive \windows" into
the regulation of the heart.
Current methods for estimating autonomic nerve ac-
tivity can be characterized as largely informal, and are
based on either monitoring RR interval changes (in the
time domain) after pharmacological interventions, or var-
ious frequency domain procedures that attempt to as-
sign autonomic identity to individual power bands and
a \vagosympathetic balance" index to the ratio of high
(vagus) to low (sympathetic) frequency bands. A com-
prehensive discussion is oered by Eckberg [2] in a recent
review.
0 0
of respiratory frequency (0!0.5 Hz) shows a number of
typical nonlinear interactions such as frequency locking
around 10-second respiration.
means are immune only to small deviations from the op-
erating point, as pointed out by their authors.
A recent detailed nonlinear model of cardiovascular
and respiratory interaction was proposed by Seidel and
Herzel [6]. The model contains 4 ODEs with 3 pure time-
delays, exponential and saturation nonlinearities, giving
a wide spectrum of complex dynamics.
Figure 1 shows a spectrogram constructed by making
many runs of the Seidel-Herzel model, each at a dier-
ent respiration frequency. The power spectrum of heart
In this work, we present a rst step toward a more
formal computation of cardiac sympathetic nerve activity.
Since such a structured attempt is necessarily based on a
mathematical model of the phenomena, the next section
points to such models from the recent literature.
2 Cardiovascular System Models
Work on modeling the dynamics of the cardiovascular
system and its controls dates back to at least the 1960's,
and the very detailed models of Beneken, or Katona.
More recent models are those of Baselli, Cerutti et
al. [3], deBoer and Karemaker [4], as well as those of Saul
and coworkers [5]. A common characteristic of these mod-
els is their linearity: with the exception of occasional time-
rate data is shown. The heart rate response to respiration
is seen to consist of several elements. Part of the heart
rate response occurs at the same frequency as respiration
| this is the large diagonally sloping ridge in the spec-
trogram. Another ridge occurs at approximately 0.1 Hz,
independent of respiration frequency, and arises from a
nonlinear limit cycle in the model. This 0.1 Hz limit cycle
and respiration can be seen to interact: when respiration
is at 0.2 Hz, there is an enhanced heart rate response at
0.1 Hz, which disappears for respiratory frequencies be-
tween 0.1 and 0.2 Hz and reappears dramatically at 0.1
Hz. Such interactions stem from the nonlinear nature
of the model. Insofar as the similar interactions appear
delays, they are FDLTI (nite-dimensional linear time-
invariant) systems. Thus, the analyses performed by their
 Author to whom all correspondence should be addressed: phone
(514) 398-8092, fax (514) 398-7542, email: cmr@cnd.mcgill.ca
in human physiology [2], the use of nonlinear models is
important in interpreting heart rate and blood pressure
variability.

1
 3 Estimation of Internal Variables
Since the nonlinear model considered contains an ex- 0.6

plicit expression for sympathetic activity s in terms of

arterial blood pressure, 0.4

b = k1 (p ? po ) + k2 dp
dt ; (1)

model
s = max(0; s ? ks b + ks jsin(fr t)j);
o b r
(2) 0.2

where fr is the frequency of respiration, b is the barore-

ceptor activity, and p(t) the blood pressure, a simple esti- 0
300 310 320 330 340 350 360 370 380 390 400
mation would consist in choosing values of the parameters, time (seconds)

dierentiating the pressure signal, and using equation (2) run−E

to compute activity. In clinical situations, obtaining op-

0.8

timal values for the parameters is dicult and expensive, 0.6

while the expressions above represent only simple outlines,

estimate
or the skeleton, of the real dynamics. 0.4

A method for designing an operator to produce good

estimates of s from p(t) in face of model/parametric,
0.2

and signal uncertainty, was developed in the control area, 0

and applied successfully to many complex industrial pro-

300 310 320 330 340 350 360 370 380 390 400
time (seconds)

cesses, e.g. [7]. It is a worst-case design based on the 0.16

H1 -operator norm and a matrix function, (
), index

for robust performance [8]. In this work we used the Mat- MEAN
lab software associated with the method, -Tools [9].
0.14
STD DEV

ESTIMATED SYMPATHETIC ACTIVITY

An estimator was constructed from the linearized
model at one set of parameters fksr ; so g (point A in g- 0.12

ure 2), and this same estimator applied to runs with other, E
dierent parameter sets. Estimated sympathetic activity 0.1
can be directly compared to actual activity in the model.
There is a strong correlation between mean sympathetic
activity in the model (averaged over 100 seconds) and
0.08

estimated activity, as shown in gure 2. Similarly, the E D

standard deviations of model and estimated activity are 0.06

strongly correlated. This suggests that the nonlinearity

D

in the model does not eliminate the ability to track sym- 0.04
C
C

pathetic activity using an estimator developed with linear A B

A B

methods.
4 Concluding Remarks
0.02
0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16
MODEL SYMPATHETIC ACTIVITY

The formal method of estimation suggested here is

based on the linearization of a nonlinear model. This Figure 2: Estimated vs. model (nominal) sympathetic ac-
general procedure employs the tools of robust controller tivity. TOP: typical model and estimated time-series;
design and promises good performance despite paramet- BOTTOM: mean and standard deviation of 100-second
ric (model) and measurement (noise) uncertainty. Future long signal segments, obtained at ve dierent parameter
work will compare performance of alternative estimation sets (A,B,C,D,E). The estimator was designed to perform
methods that do not demand linearization.
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