Journal of Gerontology: BIOLOGICAL SCIENCES

1998, Vol. 53A, No. 4, B274-B280

Copyright 1998 by The Gerontological Society of America

Age-Related Changes of Arterial Mechanical

Properties in Rats: Analysis Using Exponentially
Tapered T-Tube Model
Kuo-Chu Chang, Yuan-Feen Tsai, Chai-Yee Chow, Ying-I Peng, and Tong-J Chen
Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.

T has been suggested that arterial physical properties,

such as elasticity and distensibility, change with age
(1-4). Histological alterations of the vasculature, including
the degeneration of smooth muscles in the media, the fragmentation and decrease of elastic fibers, and increases of
irregularly arranged collagen fibers in the stroma, become
obvious in elderly populations (5). In humans, the changes
of the mechanical properties occur primarily in large vessels. The stress-strain data of blood vessels show an increase in the elastic modulus or a decrease in the distensibility of aged human vasculature (6-8). The changes in
aging dog seem to be similar to those in human (9,10).
However, the age-related changes in the rabbit are opposite
to those reported in human (11). Contradictory observations were reported in rats, showing no change (12), an
increase (13), or a decrease (14) in the elastic modulus with
age. These data seem to suggest that the variance may be
caused by the difference in species or analytical methods.
Because the mechanical properties of the vasculature can
be reflected in the aortic pressure-flow relation, measurements of the aortic input impedance are regarded as essential for the analysis of the arterial mechanics (15-18). Both
model-independent and model-based approaches have been
adopted to obtain the aortic input impedance. The modelindependent approach, such as Fourier series expansion of
the aortic pressure and flow signals, involves direct
description of the arterial mechanics (15,16). This approach
tends to be purely observational and may overlook the
complexity of the distributed vasculature. The model-based
approach, such as wave transmission model based on Ttube topology, has been used to explain the arterial wave

B274

propagation and reflection phenomena (19,20). However,

in the mammalian arterial system, the nature of the vasculature is nonuniformity (16,18,21). In earlier analysis, the
changes of vascular diameter and elastic tapering have not
been taken into consideration. A new approach with the
exponentially tapered T-tube model was developed recently
to relate the pulsatile pressure and flow waves measured in
the ascending aorta (22). The method can reflect the physiological behavior of arterial diameter and elastic tapering
and is considered as a proper mean to analyze aortic input
impedance. The analysis will provide insightful information of the wave transmission in the arterial system.
Earlier studies on the changes of vascular physical properties to rats showed great diversity in response to age.
Therefore, the purpose of this study was to reexamine the
changes of rat's arterial mechanical properties in relation to
age by using the exponentially tapered T-tube model. The
aortic characteristic impedance, arterial load compliance,
vascular tapering index, and amplitude as well as timing
of pulse wave reflection were analyzed to delineate the
changes in arterial mechanical properties.
MATERIALS AND METHODS

Subjects
The specific pathogen-free male Long-Evans rats used in
this study were obtained from the colony maintained in the
barrier facilities at the Animal Center of Medical College,
National Taiwan University. All rats were allowed free
access to the Purina chow and water and housed two to
three per cage in a 12-h light/dark cycle animal room. Peri-

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This study was designed to explore the changes of mechanical properties in the rat's arterial system at different ages
by using the exponentially tapered T-tube model. Long-Evans male rats at the ages of 6, 12, and 18 months were
anesthetized and thoractomized. Rats at the ages of 6, 12, and 18 months were individually referred to as young,
adult, and middle-aged rats. The pulsatile pressure and flow signals in the ascending aorta were measured by a
high-fidelity pressure sensor and electromagnetic flow probe, respectively. Model parameters, such as aortic characteristic impedance, vascular tapering index, wave transit time, and arterial load compliance, were inferred from the
aortic pressure and flow signals to describe the pulsatile nature of blood flows in the vasculature. The static hemodynamic condition in those animals with different ages was characterized by (i) no change in cardiac output and (ii)
a decrease in heart rate, arterial blood pressure, as well as total peripheral resistance. As for the pulsatile nature of
the arterial system, the wave transit time remained unaltered, indicating there was no change in the aorta's distensibility of rats at those three different ages. The arterial load compliance, which describes the buffering nature of a
hollow vessel, also remained unchanged. On the contrary, there was a significant fall in aortic characteristic
impedance in those age-related rats. The decline of aortic characteristic impedance without a significant change in
arterial distensibility suggests that lumen growth of the aorta and large arteries may occur in rats up to middle age.

VASCULAR DYNAMIC CHANGES IN AGE-RELATED RATS

odic checks of the cages and body weights ensured that the
food was administered properly. Rats at the ages of 6 (n =
10), 12 (n = 10), and 18 months (n = 10) were anesthetized
and thoractomized for the study of age-related changes in
arterial mechanical properties. Rats at the ages of 6, 12, and
18 months were referred to as young, adult, and middleaged rats, respectively.

Model Parameters Inferred by the Exponentially Tapered

T-Tube Model
All model parameters were estimated and analyzed by
the exponentially tapered T-tube model according to the
procedure described previously (22). In brief, an asymmetric T-tube model with vascular nonuniformity was used to

relate the pulsatile pressure and flow waves in the ascending aorta. The nonuniform T-tube model and its terminal
complex load are shown in Figure 1. This model consists of
two sections of different lengths. The shorter section represents the circulation of head, neck, and upper limbs (head
or upper body circulation), and the longer section represents the circulation of trunk and lower limbs (body or
lower body circulation). The subscripts h and b represent
the head and body circulation, respectively. Properties of
the ith tube, / equals h or b, include a characteristic impedance (Zci) at the entrance of the tube and a transmission
time (T,). T, is the time for a wave to propagate from one
end of the tube to the other. Properties of the load are given
by the load elements that are high-frequency tube-matching
impedance element (/?,), load compliance (Cu), and terminal resistance (/?,) The relation between the characteristic
impedance at the distal end of the tube and that at the
entrance of the tube is quantified by the tapering index
(^^oOw-^oo (22). In this system, the parallel combination of
the head circulation and body circulation is defined as the
global circulation. Peripheral resistance of the global circulation (Rp) was calculated as mean pressure divided by
mean flow. The terminal resistance of each tube was computed by using the upper-to-lower body resistance ratio of
2.33 for normotensive state and 3.17 for hypotensive state
(see Appendix, Note 1). With setting (^Go^o)-^ equal to
(#I.6O<,)<D->OO, the model parameters, such as aortic characteristic impedance (Zc), vascular tapering index (qQ0)oi^,
wave transit time (T^T*), and arterial load compliance
(Cu,,Cu,), were estimated by using the equations developed
for the exponentially tapered T-tube model. The characteristic impedance at the inlet of each tube was calculated by
using the upper-to-lower body characteristic impedance
ratio of 1.14 for normotensive condition and 1.20 for
hypotensive condition (see Appendix, Note 2). The high-frequency tube-matching impedance was determined by the
characteristic impedance, tapering index, and terminal resistance (22). The time domain reflection factor was derived as
the amplitude ratio of backward-to-forward peak pressure
wave according to previously described methods (27).
Therefore, the wave reflection phenomenon was characterized by the wave transit time and the wave reflection factor.
In the process of model parameter estimation, the measured aortic pressure was taken as the output variable
whereas the measured aortic flow was the model input variable. Parameters of the model were adjusted to minimize
the normalized root-mean-square error (e*), using the
Nelder-Meade Simplex algorithm (28). The model parameters leading to the minimum of e* were taken as the model
estimates of arterial mechanical properties. In one rat,
examples of the measured (solid lines) flow wave and pulsatile pressure in the ascending aorta and the mathematically predicted (dashed lines) results were shown in the top
of Figure 2. The input impedance spectra of the same rat
were shown in the bottom of Figure 2. The solid lines represented the model-generated spectra, and the circles were
data points obtained from the ratio of the ascending aortic
pressure harmonics to the corresponding flow harmonics.
The aortic impedance spectra of the measured and mathematically deduced results were similar.

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Catheterization
Each rat was anesthetized with sodium pentobarbital (35
mg/kg, i.p.). The femoral vein was cannulated for the
administration of supplemental pentobarbital (30 mg/kg
every 2 h). Tracheotomy was performed to provide artificial
ventilation with a tidal volume of 6-8 ml/kg and respiratory
rate of 50-70 breaths/min (23,24). The chest was opened
through the right second intercostal space. An electromagnetic flow probe (model 100 series, internal circumference 8
mm, Carolina Medical Electronics, King, NC) was placed
around the ascending aorta to measure the pulsatile aortic
flow. A Millar catheter with a high-fidelity pressure sensor
(model SPC 320, size 2F, Millar Instruments, Houston, TX)
was used to measure pulsatile aortic pressure. Before inserting the catheter, the pressure sensor was prewarmed in 37C
saline for at least 1 h. The catheter was inserted via the isolated right carotid artery into the ascending aorta. The
catheter tip position of the pressure transducer was adjusted
1-2 mm distal to the downstream edge of the electromagnetic flow probe to avoid interference with the flow measurements. After withdrawing the catheter from each rat, the
catheter was reimmersed in the bath to check for baseline
drift. At the end of the experiment, the pressure reading
from the sensor barely submerged in the saline at atmospheric pressure and room temperature was used as the zero
pressure reference (25). Timing between the pulsatile pressure and flow signals, due to spatial distance between the
flow probe and proximal aortic pressure transducer, was corrected by a time-domain approach, in which the foot of the
pressure waveform was realigned with that of the flow (26).
The electrocardiogram (ECG) of lead II was recorded with a
Gould (Cleveland, OH) ECG/Biotach amplifier. The analogue waveforms were sampled at 500 Hz by using a 12-bit
simultaneously sampling analog-to-digital (A/D) converter
interfaced to a personal computer. Selection of signals (5-10
beats at steady state) was made on the basis of the following
criteria: (i) recorded beats with optimal velocity profile that
was characterized by a steady diastolic level, maximal systolic amplitude, and minimal late systolic negative flow; (ii)
beats with an RR interval, cardiac cycle length, less than 5%
different from the average value for all recorded beats; and
(iii) exclusion of ectopic and postectopic beats. The selective beats were averaged in the time domain, using the peak
R wave, the peak wave of QRS, of ECG as a fiducial point
and were subjected for further analysis.

B275

CHANG ETAL.

B276

Head End
Complex Load

'ch

Complex Load

Complex Load

Body End
Figure 1. T-tube arterial system model with asymmetric head and body circulation paths. Each path consists of a nonuniform lossless transmission tube
and a complex terminal load. Properties of each tube include an input characteristic impedance Z and a characteristic delay time Ti for wave transmission
from one end of the tube to the other. The quantity exp((^0o)a)-+oo) is used to relate the characteristic impedance at the distal end of the tube to that at the
inlet of the tube. Complex loads possess /?,, Cu, and Rpi as described in the text [from Chang and Kuo (22)].

Fitness of the data generated by the model was judged by

the magnitude of e* and by indices from a linear regression
of the model-generated pressure on the measured pressure.
Two indices were used to evaluate the goodness-of-fit: (i) the
coefficient of determination r\ and (ii) the standard error of
the estimate SEE. We looked for r2 to be close to 1 and for
SEE to be of order of 1% when expressed relative to the
mean of all pressure observations. A summary of the measures indicating goodness of the exponentially tapered T-tube
model fits was given in Table 1. Sensitivity analysis on the
model parameters was also performed to give insight into
these estimators (29). The relative standard error of the
parameters over all experimental rats were as follows: 5.4
1.4% for T, 3.8 1.6% for T, 5.2 1.9% for Cu,, 5.2 1.5%
for Cu,, 1.8 0.7% for Zc, and 6.4 2 . 1 % for (g0o)a>->oo.
These results indicated that all model parameters were estimated with good accuracy in analyzing the systemic arterial
system with the exponentially tapered T-tube model.
Statistics
Results were expressed as means SE. When multiple
comparisons were made for the age effect on the arterial
mechanical properties, statistical significance was determined by analysis of variance (ANOVA). Significant differ-

ences were assumed at the level of/? < .05. If ANOVA for a
hemodynamic variable reached the significant level, then
the Tukey method was used to determine the groups of rats
having different mean values of the variable.
RESULTS

The effect of age on body weight, heart rate, arterial

blood pressure, and cardiac output was shown in Table 2.
Body weight was similar between 12- and 18-month-old
rats and was significantly smaller in 6-month-old rats. A
significant decrease in heart rate, systolic, diastolic, and
mean arterial blood pressure was observed in 18-month-old
rats relative to 12-month-old rats. Cardiac output was not
changed in rats at the ages of 6, 12, and 18 months. However, total peripheral resistance was significantly decreased
in 18-month-old rats.
Table 3 lists the global vascular parameters that were
estimated by the exponentially tapered T-tube model. Rats
at 18 months old had a significant fall in aortic characteristic impedance, whereas rats between 6 and 12 months old
had no significant change in this parameter. Vascular tapering index, wave reflection factor, and total load compliance
were similar among rats at the ages of 6, 12, and L8
months. The pulsatile nature of blood flows in each tube

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PC)

B277

VASCULAR DYNAMIC CHANGES IN AGE-RELATED RATS

100

150

200

Time (msec)

20

50

100

150

200

Time (msec)

40

60

Frequency (Hz)

20
Frequency (Hz)

Figure 2. Example of pulsatile waves and aortic input impedance in one rat. (Top) Pressure and flow signals measured in the ascending aorta (solid
lines); pressure predicted by the exponentially tapered T-tube model (dashed line). (Bottom) Input impedance spectra of head circulation (dashed lines),
body circulation (dotted lines), and global circulation (solid lines), as represented by the exponentially tapered T-tube model. Data points obtained from
the ratio of ascending aortic pressure harmonics to the corresponding flow harmonics (circles).

Table 1. Indexes of Fitness for the Exponentially Tapered T-Tube

Model-Derived Data to 6-, 12-, and 18-Month-Old Rats
Age (month)
Rats
Normalized root-meansquare error (e*) (X10 J )
Standard error of the
estimate (%)

6(n=10)

12 (n = 10)

18 (/i = 10)

6.16 .49

5.86 .57

6.19 .28

.91 .24

.95 .22

.99 .17

Coefficient of determination .9902 .0017 .9899 .0016 .9896 .0014

Notes: All values are expressed as means SE. These indexes are the
linear regression parameters of the model output pressure over the measured pressure.

and terminal load, represented by wave transit time and

arterial load compliance, respectively, were inferred by the
exponentially tapered T-tube model; they are summarized
in Table 4. There was no significant change in wave transit
time in the head and body circulation among rats at those
three different ages. Similar was the arterial load compliance in the head and body circulation of those three groups

of rats. From Tables 2-4 we drew the results that no significant changes were found in the static and oscillatory components of the ventricular afterload inposed on the heart,
when comparison was made only on rats between 6 and 12
months old. These data suggest that the functions of Winkessel and resistance vessels were not modified between
rats at the ages of 6 and 12 months.
We also performed a power analysis to discuss the size of
the difference that would be theoretically important and to
indicate what size of difference could actually be detected
with 80% power. We took CL as an example to delineate
this idea. For CL there was a complete nonsignificant age
difference. Because its standard deviation was about .65,
we could detect a difference on the order of 2.56, 3.00, and
3.54 across the ages with 80% power. A change any smaller
than this would not be of much theoretical importance, so
we feel that this result shows that there is no important age
change in this variable. For Zc it exhibited changes with
age, but not significantly between 6- and 12-month-old animals. The power analysis pointed out that the smallest true
mean difference was about .42 with 80% probability using
the F test between 6- and 12-month-old rats. The analysis

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50

B278

CHANG ETAL.

Table 2. Basic Hemodynamic Data Measured and Calculated in 6-, 12-, and 18-Month-Old Rats
Age (month)

p- Value

Rats

6 (n = 10)

12 (n = 10)

18 (n = 10)

ANOVA

6vs 12

6vs 18

12 vs 18

BW
HR
P,

419.9 11.1
351.47.13
125.5 2.9
87.9 2.4
106.5 2.4
1.48 .11
75.6 5.9

503.0 15.3
346.7 8.6
127.2 2.6
93.7 3.4
110.7 3.0
1.50.ll
77.7 6.1

508.2 17.1
312.6 12.1
115.8 1.8
83.6 2.1
100.8 2.1
1.76 .07
58.2 2.9

<.001
<.O1
<.O1
<.O5
<.O5
NS
<.O5

<.O1
NS
NS
NS
NS
NS
NS

<.O1
<.O5
<.O5
NS
NS
NS
= .06

NS
<.O5
<.O1
<.O5
<.O5
NS
<.O5

Pi
Pm

CO
Rf

Table 3. Global Parameters Inferred by the Exponentially Tapered T-Tube Model in 6-, 12-, and 18-Month-Old Rats
Age (month)
Rats
Z
R;

p- Value

6 ( = 10)

12 (n = 10)

18(n=10)

ANOVA

6vs 12

6vs 18

12 vs 18

3.09 .20
.1967 .013
.40 .04
2.56 .24

2.87 .19
.1939 .015
.43 .04
2.67 .19

2.10 .14
.1866 .009
.54 .06
2.72 .19

<.005
NS
NS
NS

NS
NS
NS
NS

NS
NS
NS

<.05
NS
NS
NS

Notes: All values are expressed as means SE. Zc, aortic characteristic impedance (mmHgmin/ml); (qQo)(ji-*, tapering index; /?/, wave reflection factor, CL, peripheral load compliance (ul/mmHg); NS, not significant (p > .05).

Table 4. Peripheral Load Compliance and Wave Transit Time of the Head and Body Circulation Estimated
by the Exponentially Tapered T-Tube Model in 6-, 12-, and 18-Month-Old Rats
Age (month)
Rats

6 (n = 10)

12 (n= 10)

p- Value
18(n=10)

ANOVA

6vs 12

6vs 18

12 vs 18

Head circulation
Peripheral load
Cu,

.48 .07

.49 .06

.43 .03

NS

NS

NS

NS

3.85 .64

4.50 .93

5.24 .62

NS

NS

NS

NS

Transmission tube
Body circulation
Peripheral load
Cu,

2.08 .23

2.18 .17

2.29 .20

NS

NS

NS

NS

26.69 .98

24.79 .68

25.29 .88

NS

NS

NS

NS

Transmission tube
Tj,

Notes: All values are expressed as means SE. Cu, and Cu,, peripheral load compliance in the head and body circulation, respectively (ul/mmHg);
T and T, wave transit time in the head and body circulation respectively (ms); NS, not significant (p > .05).

reported that if there was a true mean drop of .42 in Zc then

the study has a good chance of detecting it. If the true mean
change were smaller, the study could more easily miss it.
DISCUSSION

This is the first report of using the exponentially tapered

T-tube model to analyze the changes of arterial physical
properties in rats at the ages of 6, 12, and 18 months. The
impedance is determined by the physical characteristics of
the vasculature, including its elastic properties and size, as
well as by the viscosity and density of the fluid contained
within (15,16). Both model-independent and model-based
approaches have been adopted to study aortic input impedance. Because of the arterial distribution, a model-based

approach, such as a succinct T-tube model, is more approapriate for the exploration of the pulsatile nature of blood
flows in the vasculature. Because the diameter and elastic
tapering are of importance in the arterial system (16,18,21),
the smooth change of vascular impedance, caused by these
tapers, must have substantial impact on the magnitude
and/or timing of pulse wave reflection. The diameter and
elastic tapering of the vasculature were taken into consideration in the present study to analyze the changes of vascular
dynamics in rats at those three different ages.
The static hemodynamic condition in rats at the ages of
6, 12, and 18 months was characterized by (i) no change in
cardiac output and (ii) a decline in heart rate, systolic, diastolic, as well as mean arterial blood pressure. There was a

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Notes: All values are expressed as means SE. BW, body weight (g); HR, heart rate (beats/min); P,, systolic pressure (mmHg); Pd, diastolic pressure
(mmHg); Pm, mean pressure (mmHg); CO, cardiac output (ml/min); Rp, total peripheral resistance (mmHg*min/ml); NS, not significant {p > .05).

VASCULAR DYNAMIC CHANGES IN AGE-RELATED RATS

Just as the elastic modulus is an expression employed to

characterize material properties, so distensibility is a term
used to describe the elastic behavior of a hollow vessel or
chamber. However, compliance and distensibility are quite
different, for compliance is equal to distensibility times
volume (33). In the present study, there were no significant
changes in arterial load compliance among rats at the ages
of 6, 12, and 18 months. No significant changes in arterial
compliance and distensibility suggest that arterial blood
volume may remain unaltered in rats at those three different

ages. However, there were few data in the literature to

describe the blood volume in systemic arterial trees in rats.
Further studies on the changes of arterial blood volume in
age-related rats are needed to delineate the age effect on
homeostasis of the body fluid.
Some limitations of the current study deserve consideration. In this report, the results pertained only to measurements made in the open-chest rat with anesthesia. This setting induced a fall in blood pressure and may introduce
reflex effects not found in the close-chested setting (25). Just
how much anesthesia and thoractomy affect pulsatile hemodynamics in rats was uncertain. However, studies on other
animal models suggest that the effects are small relative to
biological and experimental variability between animals (9).
The major conclusions arising from this study are as follows: (i) Up to middle age in rats, there is a significant fall
in heart rate, arterial blood pressure, total peripheral resistance, and aortic characteristic impedance; (ii) The ageassociated increase in arteriolar caliber in rats may be the
factor responsible for the decrease of total peripheral resistance and therefore the decrease of mean arterial blood pressure; (iii) The decline of aortic characteristic impedance
without significant change in wave transit time suggests that
lumen growth of the aorta and large arteries may occur in
rats up to the middle age.
ACKNOWLEDGMENTS

This study was supported by grants from the National Science Council
(NSC 86-2314-B-002-093-M04). We greatly thank Miss Mei-Yun Tai for
the experimental preparation of this study.
Address correspondence to Dr. Kuo-Chu Chang, Department of Physiology, College of Medicine, National Taiwan University, No. 1, Sec. 1,
Jen-Ai Rd., Taipei, Taiwan.
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centrifugal waves are present at the origin (16). Characteristic impedance is directly related to the blood density and
pulse wave velocity and is inversely related to the lumen
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wave velocity. Thus, the net result of age on aortic characteristic impedance would be dependent on the relative influence of these counter-balancing factors.
Rats aged 18 months had a significant fall in aortic characteristic impedance. Similarly, Cox (13) calculated the characteristic impedance in rat carotid arteries and found that the
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in the elastic modulus with age in rats. In the present study,
the wave transit time in the head and body circulation, which
is inversely determined by the pulse wave velocity, remained
unchanged in 18-month-old rats. No significant change in
wave transit time reflected that the aorta and large arteries in
18-month-old rats were as distensible as those in 6- and 12month-old rats. The decline of aortic characteristic impedance without significant change in arterial distensibility
suggests that lumen growth of the aorta and large arteries
occurred in rats up to the middle age.

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Received April 1, 1997
Accepted February 11, 1998

Appendix
Note 1
The upper-to-lower body resistance ratio can be determined
when the ratio Kaa between measured descending thoracic aorta
mean flow and cardiac output is calculated (20). Under basal condition, approximately 67% of cardiac output in rats consisted of
blood flows in kidneys, spleen, small and large intestines, liver,
stomach, diaphragm, hindlimb muscles and bones, and skin (34).
If blood flow of other tissue and organ in the lower portion of the
body was included, it was speculated that Kd,a in the rat would be
similar to that in the dog [70% in Campbell's report (35)]. From a
comparative physiological point of view, the ratio of Kd,a in rats
was then assumed to be 0.7, .62, and .76 as in dogs under basal,
vasoconstricted, and vasodilated conditions, respectively (35).
Being calculated by the equation of RPJRPb = KdJ(\-Kdla), the
upper-to-lower body resistance ratio was 2.33 for normotensive
state and 3.17 for hypotensive state.
Note 2
The aortic characteristic impedance Zc can be measured by
many different methods. One method is to calculate Zc by averaging high-frequency moduli of impedance data points obtained from
the ratio of the corresponding harmonics of pressure and flow.
From knowledge of Zc, the ratio of upper-to-lower body characteristic impedance Ku, could be inferred by the exponentially tapered
T-tube model. In that case, the ratio of upper-to-lower body characteristic impedance rather than the aortic characteristic impedance
remained to be estimated. With 10 rats, we have separately determined Khb for basal, vasoconstricted (0.5 mg/kg methoxamine, n =
5), and vasodilated (0.5 mg/kg prazosin, n = 5) conditions. The
ratio of upper-to-lower body characteristic impedance was estimated to be 1.142 .083, 1.375 .105, and 1.203 .088 for basal,
vasoconstricted, and vasodilated states, respectively.

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CHANG ETAL.