Am J Physiol Heart Circ Physiol 283: H792–H799, 2002.
First published April 4, 2002; 10.1152/ajpheart.00025.2002.
Myocardial function defined by strain rate and strain
during alterations in inotropic states and heart rate
FRANK WEIDEMANN, FADI JAMAL, GEORGE R. SUTHERLAND, PIET CLAUS,
MIROSLAW KOWALSKI, LIV HATLE, IVAN DE SCHEERDER,
BART BIJNENS, AND FRANK E. RADEMAKERS
Department of Cardiology, University Hospital Gasthuisberg, B-3000 Leuven, Belgium
Received 14 January 2002; accepted in final form 26 March 2002
myocardial contraction; contractility; echocardiography
eters can now be derived noninvasively using validated
ultrasound techniques (12, 24). Recent studies have
investigated the accuracy of these two deformation
parameters for the assessment of ischemia-induced
myocardial dysfunction (12–14, 24–25). It has been
shown that the regional magnitude of deformation is
related to global ejection performance as assessed by
stroke volume (SV) (15) and ejection fraction (26). In
addition, because the magnitude of deformation is influenced by both heart rate (HR) and loading conditions (24, 26), it does not only reflect the inotropic
status of the myocardium. We hypothesized that SRsys
might better reflect the change in myocardial contractility.
Thus the aim of the study was to investigate, in a
closed-chest pig model, how the two regional deformation parameters, ⑀sys and SRsys, are related to left
ventricular (LV) contractility and SV over a wide range
of HR and during varying positive or negative sympathetic pharmacological stimulation in normal myocardium.
METHODS
Twenty cross-bred pigs (weight 31 ⫾ 4 kg) were anesthetized using intravenous propofol (0.3 mg 䡠 kg⫺1 䡠 min⫺1) and
fentanyl (0.5 ␮g 䡠 kg⫺1 䡠 min⫺1) and ventilated with a mixture
of air and oxygen. All animals were treated in accordance
with the National Institutes of Health Guide for the Care and
Use of Laboratory Animals.
Experimental Preparation
of regional myocardial
function is usually based on the evaluation of local
deformation both in the experimental (4, 24) and clinical settings (4, 10, 12, 22). Systolic function could be
characterized by two regional deformation parameters
(8, 12, 24, 25): 1) regional systolic strain (⑀sys), which
represents the magnitude of myocardial deformation
from a reference point (usually end diastole) to end
systole and 2) peak systolic strain rate (SRsys), which
represents the maximal velocity of deformation during
mechanical systole (8). These two deformation param-
LV pressure (LVP) and its first derivative (dP/dt) were
measured with the use of a micromanometer-tipped catheter
(Millar) calibrated against a mercury column. The catheter
was positioned in the LV cavity via the left carotid artery.
Analog signals were digitized using commercially available
software (Windaq). A unipolar pacemaker lead was passed
via the right jugular vein and positioned in the right atrium
to allow controlled right atrial pacing.
Address for reprint requests and other correspondence: F. Rademakers, Dept. of Cardiology, Univ. Hospital Gasthuisberg, Herestraat 49,
B-3000 Leuven, Belgium (E-mail: [email protected].
ac.be).
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby
marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
THE
H792
NONINVASIVE
ASSESSMENT
Ultrasonic Data Acquisition
Echocardiographic studies were performed using a Vingmed System 5 (GE Ultrasound) and a 2.5-MHz transducer.
0363-6135/02 $5.00 Copyright © 2002 the American Physiological Society
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Weidemann, Frank, Fadi Jamal, George R. Sutherland, Piet Claus, Miroslaw Kowalski, Liv Hatle, Ivan
De Scheerder, Bart Bijnens, and Frank E. Rademakers. Myocardial function defined by strain rate and strain
during alterations in inotropic states and heart rate. Am J
Physiol Heart Circ Physiol 283: H792–H799, 2002. First
published April 4, 2002; 10.1152/ajpheart.00025.2002.—For
porcine myocardium, ultrasonic regional deformation parameters, systolic strain (⑀sys) and peak systolic strain rate
(SRsys), were compared with stroke volume (SV) and contractility [contractility index (CI)] measured as the ratio of endsystolic strain to end-systolic wall stress. Heart rate (HR)
and contractility were varied by atrial pacing (AP ⫽ 120–180
beats/min, n ⫽ 7), incremental dobutamine infusion (DI ⫽
2.5–20 ␮g 䡠 kg⫺1 䡠 min⫺1, n ⫽ 7), or continuous esmolol infusion (0.5 mg 䡠 kg⫺1 䡠 min⫺1) ⫹ subsequent pacing (120–180
beats/min) (EI group, n ⫽ 6). Baseline SRsys and ⑀sys averaged 5.0 ⫾ 0.4 s⫺1 and 60 ⫾ 4%. SRsys and CI increased
linearly with DI (20 ␮g 䡠 kg⫺1 䡠 min⫺1; SRsys ⫽ 9.9 ⫾ 0.7 s⫺1,
P ⬍ 0.0001) and decreased with EI (SRsys ⫽ 3.4 ⫾ 0.1 s⫺1,
P ⬍ 0.01). During pacing, SRsys and CI remained unchanged
in the AP and EI groups. During DI, ⑀sys and SV initially
increased (5 ␮g 䡠 kg⫺1 䡠 min⫺1; ⑀sys ⫽ 77 ⫾ 6%, P ⬍ 0.01) and
then progressively returned to baseline. During EI, SV and
⑀sys decreased (⑀sys ⫽ 38 ⫾ 2%, P ⬍ 0.001). Pacing also
decreased SV and ⑀sys in the AP (180 beats/min; ⑀sys ⫽ 36 ⫾
2%, P ⬍ 0.001) and EI groups (180 beats/min; ⑀sys ⫽ 25 ⫾ 3%,
P ⬍ 0.001). Thus, for normal myocardium, SRsys reflects
regional contractile function (being relatively independent of
HR), whereas ⑀sys reflects changes in SV.
H793
REGIONAL MYOCARDIAL DEFORMATION
B-mode color Doppler myocardial imaging (CDMI) data were
acquired using parasternal short-axis views at a frame rate
of 180 frames/s. Pulse repetition frequency was adjusted to
avoid aliasing, and three consecutive heart cycles during
brief apnea were recorded.
Experimental Protocol
Data Analysis
Echocardiographic CDMI data. CDMI data were analyzed
using dedicated software (TVI, GE Ultrasound) as previously
described (14). Briefly, radial strain rate was estimated by
measuring the spatial velocity gradient over a computation
area of 5 mm. The region of interest was continuously positioned within the LV posterior wall. A septal myocardial
velocity profile was used for the timing of end diastole (onset
of isovolumic contraction) and end systole (aortic valve closure) (14).
Strain rate profiles were averaged over three consecutive
cardiac cycles and integrated over time to derive the natural
strain profile using end diastole as the reference point
(Speqle, K. U. Leuven) (8). From the averaged strain rate and
strain data, SRsys and ⑀sys were calculated (Fig. 1).
Echocardiographic gray-scale data. From the same CDMI
data sets, high-resolution digital gray-scale B-mode data
could be displayed after the subtraction of the color myocardial velocity data from the clips. The myocardial end-diastolic
and end-systolic wall thickness and LV diameters were measured from an anatomic M-mode tracing. End-diastolic and
end-systolic LV volumes were calculated using the Teichholz
equation (23)
V⫽
7 䡠 D3
2.4 䡠 D
Hemodynamic data. The maximal rate of pressure development (⫹dP/dtmax) and pressure fall (⫺dP/dtmax) was used
for the evaluation of global contractile function and ventricular relaxation.
The meridional wall-stress of the posterior wall was estimated assuming an ellipsoid LV geometry (9)
␴⫽
冋
册
P 䡠 D2
䡠 0.133
4 䡠 h共D ⫹ h兲
where ␴ is wall stress (in kPa), P is the LVP (in mmHg), h is
the posterior wall thickness (in mm), D is the LV cavity
minor axis (in mm), and 0.133 is a conversion factor from
mmHg to kPa.
␴ was calculated at end systole (␴es) and end diastole (␴ed)
to estimate the relative changes in afterload and preload,
respectively.
The regional contractile function of the posterior wall was
evaluated using a contractility index (CI; in kPa⫺1) calculated as the end-systolic strain-to-stress ratio (3, 16)
⑀ sys
CI ⫽ ␴
es
where ⑀sys is the systolic strain (in %) and ␴es is the endsystolic wall stress (in kPa).
Statistical Methods
Data are presented as means ⫾ SE. Multiple comparisons
were performed using ANOVA with a post hoc Duncan’s test.
A linear Pearson correlation was used to compare the deformation parameters with the volume and hemodynamic parameters. A forward stepwise (F to enter ⫽ 10) multiple
regression analysis with SV, ⫹dP/dtmax, HR, ␴ed, and ␴es as
independent variables and SRsys and ⑀sys as dependent variables was used. CI was not included in the independent
variables because it is calculated by the dependent parameter ⑀sys. Statistical significance was inferred for P ⬍ 0.05.
RESULTS
where V is the LV volume and D is the short-axis LV diameter.
LV SV was calculated as
SV ⫽ LVEDV ⫺ LVESV
where LVEDV is the LV end-diastolic volume and LVESV is
the LV end-systolic volume.
AJP-Heart Circ Physiol • VOL
Fig. 1. A: normal strain rate (SR) profile during 1 cardiac cycle of left
ventricular (LV) radial deformation, derived at baseline (BS) from
the posterior wall. Arrow, measurement point used for peak systolic
SR (SRsys) estimation. B: normal radial strain profile during 1 cardiac cycle derived from the posterior wall by integrating the SR
curve. Arrow, systolic strain. AVC, aortic valve closure.
Five CDMI data sets (4%) were subsequently excluded from the analysis because of reverberation artifacts.
The hemodynamic data for each of the three groups
are presented in Table 1. At baseline, there were no
significant differences in HR, LV end-diastolic pressure (LVEDP), LV end-systolic pressure (LVESP),
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After 20 min of stabilization, hemodynamic and echocardiographic data were acquired. The animals were divided
into the following three groups.
Group 1: control atrial pacing group. The control atrial
pacing (AP) group (n ⫽ 7) underwent incremental right AP
(120, 140, 160, and 180 beats/min). For each stage, continuous AP was done for 5 min before CDMI and hemodynamic
data acquisition.
Group 2: dobutamine infusion group. The dobutamine infusion (DI) group (n ⫽ 7) had incremental positive inotropic
stimulation (sequentially 2.5, 5, 10, and 20 ␮g 䡠 kg⫺1 䡠 min⫺1).
Each dose was given over 5 min by continuous intravenous
administration before data acquisition.
Group 3: esmolol infusion group. The esmolol infusion (EI)
group (n ⫽ 6) underwent negative inotropic stimulation induced by an intravenous infusion of esmolol (0.5 ⫾ 0.15
mg 䡠 kg⫺1 䡠 min⫺1) to achieve a HR reduction of 20%. After HR
and blood pressure stabilization, incremental right AP was
performed (to achieve 120, 140, 160, and 180 beats/min). For
each stage, during continuous EI, AP was done for 5 min
before data acquisition. During the study, the underlying
native HR was checked during intermittent brief episodes
when pacing was stopped.
Hemodynamic and CDMI data were recorded at each step
in all three groups.
H794
REGIONAL MYOCARDIAL DEFORMATION
Table 1. Hemodynamic data in the AP, DI, and EI groups
Peak ⫹dP/dt
LVESP
Peak ⫺dP/dt
HR
LVEDP
Baseline
AP
120 beats/min
140 beats/min
160 beats/min
180 beats/min
110 ⫾ 3
12 ⫾ 1
78 ⫾ 3
1,720 ⫾ 96
⫺2,500 ⫾ 96
120
140
160
180
11 ⫾ 1
9 ⫾ 1†
6 ⫾ 1*
5 ⫾ 1*
84 ⫾ 3
83 ⫾ 4
82 ⫾ 5
78 ⫾ 5
1,740 ⫾ 121
1,730 ⫾ 80
1,800 ⫾ 93
1,815 ⫾ 102
⫺2,786 ⫾ 243
⫺2,750 ⫾ 160
⫺2,841 ⫾ 150
⫺2,706 ⫾ 170
Baseline
DI
2.5 ␮g 䡠 kg⫺1 䡠 min⫺1
5 ␮g 䡠 kg⫺1 䡠 min⫺1
10 ␮g 䡠 kg⫺1 䡠 min⫺1
20 ␮g 䡠 kg⫺1 䡠 min⫺1
107 ⫾ 3
12 ⫾ 1
77 ⫾ 3
1,690 ⫾ 95
⫺2,756 ⫾ 355
122 ⫾ 3†
141 ⫾ 3*
160 ⫾ 4*
178 ⫾ 5*
12 ⫾ 1
9 ⫾ 1†
6 ⫾ 1*
5 ⫾ 1*
85 ⫾ 6
84 ⫾ 6
82 ⫾ 3
81 ⫾ 3
2,473 ⫾ 151*
3,369 ⫾ 178*
3,967 ⫾ 149*
4,592 ⫾ 159*
⫺3,099 ⫾ 292
⫺3,430 ⫾ 317
⫺3,738 ⫾ 213†
⫺3,915 ⫾ 252†
111 ⫾ 3
90 ⫾ 4†
11 ⫾ 1
13 ⫾ 1
76 ⫾ 6
61 ⫾ 5
1,700 ⫾ 96
768 ⫾ 65*
⫺2,512 ⫾ 156
⫺1,277 ⫾ 173†
120
140
160
180
12 ⫾ 2
11 ⫾ 2
8⫾2
7 ⫾ 1†
62 ⫾ 4
64 ⫾ 6
66 ⫾ 4
65 ⫾ 6
888 ⫾ 76*
972 ⫾ 107*
1,101 ⫾ 74*
975 ⫾ 173*
⫺1,481 ⫾ 159†
⫺1,490 ⫾ 206†
⫺1,677 ⫾ 135†
⫺1,561 ⫾ 484†
AP group
DI group
Values are means ⫾ SE. AP, atrial pacing; DI, dobutamine infusion; EI, esmolol infusion; HR, heart rate (in beats/min); LVEDP, left
ventricular (LV) end-diastolic pressure (in mmHg); LVESP, LV end-systolic pressure (in mmHg); peak dP/dt, maximal rate of pressure
development (in mmHg/s); peak-dP/dt, maximal rate of pressure fall (in mmHg/s). * P ⬍ 0.001 vs. baseline; † P ⬍ 0.05 vs. baseline.
⫹dP/dtmax, and ⫺dP/dtmax among the three groups. For
each stage of DI, HR was comparable to the pacing
stages in the AP and EI groups (Table 1). ⫹dP/dtmax,
⫺dP/dtmax, and CI increased gradually in the DI group,
decreased significantly during EI, and remained constant during AP in both the AP and EI groups.
LV Volume
dial relaxation was impaired during EI, resulting in a
delayed myocardial thinning occurring mainly in late
diastole during atrial contraction.
At baseline, SRsys and ⑀sys were comparable in the
three groups, averaging 5 ⫾ 0.4 s⫺1 and 60 ⫾ 3%,
respectively. SRsys increased with DI and decreased
Table 2. Volumes in the AP, DI, and EI groups
Both LVEDV and LVESV decreased gradually in the
DI group with an increasing DI rate (Table 2). However, the SV showed a biphasic response during the DI.
SV initially increased at a low dose of dobutamine
(2.5–5 ␮g 䡠 kg⫺1 䡠 min⫺1) and then decreased at higher
doses (10–20 ␮g 䡠 kg⫺1 䡠 min⫺1) (Fig. 2). In the AP group,
the decrease was more pronounced for LVEDV than for
LVESV, resulting in a diminished SV (Fig. 2). In the EI
group, LVESV remained unchanged, whereas LVEDV
decreased with increasing HR, resulting in a decreased
SV (Fig. 2).
Myocardial Deformation
Typical examples of extracted strain and strain rate
curves at a HR of 140 beats/min from each of the three
groups are shown in Fig. 3. In all groups, strain rate
values were positive during systole and typically featured two negative peaks in diastole during early filling and atrial contraction. Strain profiles for radial
deformation showed myocardial thickening in systole
and thinning in diastole. DI resulted in an increase in
the peak systolic velocity of deformation and magnitude of deformation of the posterior wall. In contrast,
during EI, both systolic deformation parameters were
clearly reduced. In addition, during diastole, myocarAJP-Heart Circ Physiol • VOL
LVEDV
LVESV
AP group
Baseline
AP
120 beats/min
140 beats/min
160 beats/min
180 beats/min
81 ⫾ 3
43 ⫾ 2
78 ⫾ 3
72 ⫾ 3
63 ⫾ 3*
57 ⫾ 3*
40 ⫾ 2
39 ⫾ 2
38 ⫾ 2
34 ⫾ 2#
DI group
Baseline
DI
2.5 ␮g 䡠 kg⫺1 䡠 min⫺1
5 ␮g 䡠 kg⫺1 䡠 min⫺1
10 ␮g 䡠 kg⫺1 䡠 min⫺1
20 ␮g 䡠 kg⫺1 䡠 min⫺1
80 ⫾ 2
44 ⫾ 2
79 ⫾ 4
73 ⫾ 4
61 ⫾ 4*
58 ⫾ 4*
37 ⫾ 3
30 ⫾ 2*
28 ⫾ 2*
27 ⫾ 2*
EI group
Baseline
EI without pacing
EI with pacing
120 beats/min
140 beats/min
160 beats/min
180 beats/min
80 ⫾ 2
74 ⫾ 3
42 ⫾ 3
49 ⫾ 4
72 ⫾ 6
68 ⫾ 10
63 ⫾ 10†
54 ⫾ 8†
53 ⫾ 5
51 ⫾ 5
51 ⫾ 6
46 ⫾ 5
Values are means ⫾ SE. LVEDV, LV end-diastolic volume (in ml);
LVESV, LV end-systolic volume (in ml). * P ⬍ 0.001 vs. baseline;
† P ⬍ 0.05 vs. baseline.
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EI group
Baseline
EI without pacing
EI with pacing
120 beats/min
140 beats/min
160 beats/min
180 beats/min
REGIONAL MYOCARDIAL DEFORMATION
H795
changes paralleled the previously described variations
of SRsys in each group (Fig. 4).
Statistical Correlation
DISCUSSION
The finding that ⑀sys is closely related to SV and not
only to contractility is not new (15). A decrease in ⑀sys
does not necessarily reflect an alteration in regional
contractile function but can be related to increased HR
and altered loading conditions, as occurring with DI. In
contrast, this study suggests that SRsys could better
reflect the changes in myocardial contractility than
regional systolic deformation alone.
Regional Myocardial Strain
Fig. 2. Changes in regional systolic strain (⑀sys; in %) and stroke
volume (SV; in ml) in the atrial pacing (AP) group (A), the dobutamine infusion (DI) group (B), and the continuous esmolol infusion
(EI) ⫹ AP group (C). Measurements were made first at BS and then
during each step of the protocol. HR, heart rate. * P ⬍ 0.01 vs. BS
measurement.
with EI (P ⬍ 0.05). During AP, SRsys remained unchanged with increasing HR in both the AP and EI
groups (Fig. 4). Conversely, ⑀sys decreased with esmolol
and AP and had a biphasic response to dobutamine,
increasing for low dobutamine doses and decreasing for
high dobutamine doses. The changes in ⑀sys paralleled
changes in LV SV (Fig. 2).
Regional Wall Stress and Contractility
The ␴ed of the posterior wall decreased in all three
groups with increasing HR (P ⬍ 0.001). ␴es decreased
with increasing HR in both the AP and DI groups,
being more pronounced in the latter. In contrast, no
significant change of ␴es was observed in the EI group
(Table 3).
The CI was comparable at baseline for all three
groups and averaged 7.14 ⫾ 0.75 kPa⫺1. The CI
AJP-Heart Circ Physiol • VOL
Regional ⑀sys (measured at end systole) represents
the magnitude of deformation, which takes place from
end diastole (reference point) to end systole. For the
radial direction, this parameter quantifies the percentage of systolic thickening. In agreement with Morris et
al. (15), this study shows that regional ⑀sys is mainly
related to LV SV (Fig. 2). Thus, during incremental DI,
regional ⑀sys and global SV showed a biphasic response
with a significant initial increase and a decrease to
baseline values at maximal dobutamine dose. This is in
agreement with the clinical study of Pellikka et al. (18),
who observed a similar biphasic SV response in normal
patients. The initial increase in ⑀sys and SV is due to
the effects of increasing inotropic stimulation (18, 19).
Thereafter, the shortened time for ventricular filling
and the decrease in venous return (decreased LVEDV),
secondary to the dobutamine-induced increase in HR,
will result in a decrease of both SV and ⑀sys.
During incremental AP of normal myocardium, SV
decreases gradually in agreement with prior work (17,
21). The local contribution to the ejection process (i.e.,
⑀sys) also decreases, probably due to lower preload and
shortened ejection time, despite unchanged contractile
state (Fig. 2). The reduction in ⑀sys during esmolol
administration with pacing relates to the previously
mentioned factors combined with a diminished contractility. In addition, EI resulted in an abnormal ventricular relaxation, as suggested by the global decrease
in ⫺dP/dtmax. This abnormal relaxation (Fig. 3) in
combination with a shortened diastolic period during
higher HR resulted in a decreased end-diastolic volume. Therefore, global SV and thus ⑀sys decreased.
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For all the measured hemodynamic (LVEDP and
LVESP), volume (LVEDV, LVESV, and SV), contractility (CI), and wall stress parameters (␴ed and ␴es),
SRsys correlated best with CI (r ⫽ 0.84, P ⬍ 0.0001) and
⑀sys correlated best with SV (r ⫽ 0.61, P ⬍ 0.0001).
In the forward stepwise multiple regression analysis
with SRsys and ⑀sys as the dependent variable and with
SV, ⫹dP/dtmax, HR, ␴ed, and ␴es as the independent
variables, SRsys correlated best with ⫹dP/dtmax (␤ ⫽
0.81) and ⑀sys correlated best with SV (␤ ⫽ 0.48). The
results of the multiple regression analysis investigating the predictors of SRsys and ⑀sys are shown in Fig. 5.
H796
REGIONAL MYOCARDIAL DEFORMATION
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Fig. 3. An example of a typical SR and strain curve
during 1 cardiac cycle from the posterior wall in the 3
different groups. A: during AP with a HR of 140 beats/
min. B: during DI of 5 ␮g 䡠 kg⫺1 䡠 min⫺1 (equivalent of a
HR of 142 beats/min in this case). C: during continuous
EI and simultaneous AP at 140 beats/min. Note the
abnormal delayed thinning during EI due to delayed
relaxation. Dotted vertical line, AVC.
These changes of global hemodynamic are in agreement with prior pharmacological studies on the ␤-adrenoreceptor antagonist esmolol (2, 11).
In summary, for normal myocardium, systolic strain
quantifies regional systolic deformation of the LV and
is mainly determined by the ejection performance, i.e.,
the SV. The effects of a decrease in SV can offset even
a significant increase in inotropic stimulation.
Regional Myocardial Strain Rate
Strain estimation, however, does not take into account the temporal dimension, i.e., the time that is
necessary for the myocardium to achieve this deformation. In contrast, strain rate measurement quantifies
the velocity of myocardial deformation. Peak radial
SRsys, the parameter that was investigated in this
study, represents the maximal velocity of myocardial
thickening in systole (8).
Our findings in normal myocardium suggest that
changes in SRsys parallel induced changes in contractility (Fig. 4). As an in vivo parameter for contractility,
we used the ratio of end-systolic strain to end-systolic
wall stress. This parameter is known to be relatively
independent of loading and is sensitive to changes in
contractility (3, 16). During DI, myocardial contractility is mainly influenced by three different factors: 1)
the increase in inotropic state (i.e., the pharmacological effect of dobutamine) leads to an extrinsic increase
in contractility; 2) the increase in HR leads to an
additional intrinsic increase in contractility (Bowditch
effect); and 3) the decrease of preload results in an
intrinsic decrease of contractility, because the sarcomere filaments are not any longer optimally overAJP-Heart Circ Physiol • VOL
Fig. 4. Changes in regional SRsys (in s⫺1) and the ratio of end-systolic
strain-to-end-systolic wall stress (in kPa⫺1) as a contractility index (CI)
in the AP group (A), the DI group (B), and the continuous EI ⫹ AP group
(C). Measurements were made first at BS and then during each step of the
protocol. *P ⬍ 0.01 vs. BS measurement; #P ⬍ 0.001 vs. BS measurement.
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REGIONAL MYOCARDIAL DEFORMATION
Table 3. Wall stress in the AP, DI, and EI groups
LV End-Diastolic
Stress
LV End-Systolic
Stress
AP group
Baseline
AP
120 beats/min
140 beats/min
160 beats/min
180 beats/min
4 ⫾ 0.4
9.4 ⫾ 0.7
3.5 ⫾ 0.4
2.3 ⫾ 0.2*
1.2 ⫾ 0.1*
0.8 ⫾ 0.1*
8.8 ⫾ 0.7
8.1 ⫾ 0.7
6.9 ⫾ 0.6†
5.4 ⫾ 0.5†
DI group
4.2 ⫾ 0.4
9.3 ⫾ 0.7
3.3 ⫾ 0.4
2.0 ⫾ 0.3*
1.2 ⫾ 0.2*
0.8 ⫾ 0.2*
6.8 ⫾ 0.5†
5.6 ⫾ 0.4*
4.4 ⫾ 0.6*
3.7 ⫾ 0.5*
Deformation Imaging With Other Techniques
EI group
Baseline
EI without pacing
EI with pacing
120 beats/min
140 beats/min
160 beats/min
180 beats/min
3.9 ⫾ 0.3
3.6 ⫾ 0.4
9.2 ⫾ 0.7
8.1 ⫾ 1.3
2.9 ⫾ 0.5
2.4 ⫾ 0.6
1.6 ⫾ 0.5†
1 ⫾ 0.3*
8.6 ⫾ 1.7
8.4 ⫾ 1.8
8.6 ⫾ 1.7
7.2 ⫾ 1.6
effect of increased contractility due to the Bowditch
effect and decreased contractility due to the decreased
preload). Additionally, the results obtained with AP
provide evidence that the dobutamine-induced variations in strain rate are not secondary to the chronotropic effects of the drug.
In short, this study shows that SRsys is a regional
myocardial deformation parameter that, in normal
myocardium, is closely related to the changes in contractility. However, it should be noted that SRsys is not
directly measuring contractility, because it does not
take into account myocardial stress and therefore remains load sensitive.
Values are means ⫾ SE. LV end-diastolic and end-systolic stress
were measured in kPa. * P ⬍ 0.001 vs. baseline; † P ⬍ 0.05 vs.
baseline.
lapped (negative Frank-Starling mechanism). Thus
SRsys reflects on a regional myocardial level the sum of
these extrinsic and intrinsic adaptations.
Moreover, because SRsys remained constant during
the increase in HR in the AP group (Fig. 4), it would
appear to be relatively independent of HR (balanced
The regional contractile response to inotropic stimulation is complex, and therefore evaluation of the
changes in regional function requires quantitative
measurements with high temporal resolution. Magnetic resonance imaging (MRI) tagging offers the major
advantage of three-dimensional regional strain analysis (20). However, to resolve regional strain rate requires sampling rates of ⬎120 frames/s (7). Currently,
the MRI tagging technique is based on sampling rates
of 30–40 frames/s and thus can only obtain mean
strain rate (19) but not peak SRsys, which was used in
our study.
In contrast, measuring of myocardial segment
lengths in the experimental setting by sonomicrometry
(24) does provide accurate information on regional deformation properties. However, this technique requires
a sternotomy and opening of the pericardium, which
Fig. 5. Relation between regional deformation parameters (SRsys and ⑀sys) and global parameters [maximal rate of pressure development (⫹dP/dtmax), HR,
SV, LV end-diastolic wall stress (␴ed), and LV endsystolic wall stress (␴es)] using a stepwise forward
multiple regression analysis. Predicted values are
plotted versus measured values for both peak SRsys
and ⑀sys.
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Baseline
DI
2.5 ␮g 䡠 kg⫺1 䡠 min⫺1
5 ␮g 䡠 kg⫺1 䡠 min⫺1
10 ␮g 䡠 kg⫺1 䡠 min⫺1
20 ␮g 䡠 kg⫺1 䡠 min⫺1
H797
H798
REGIONAL MYOCARDIAL DEFORMATION
itself can have an impact on regional myocardial function (1, 5, 6).
Thus ultrasonic strain rate imaging is currently the
only technique that can quantify SRsys noninvasively
in vivo.
Clinical Implications
APPENDIX
This appendix describes the concepts of regional SR and ⑀
measurements and how these parameters are derived from
myocardial velocities measured with the CDMI technique.
Strain Rate
This corresponds to the rate of the deformation of an
object. Local myocardial SR (in s⫺1) can be calculated from
the spatial gradient in velocities recorded between two neighboring points in the tissue (points 1 and 2 with velocities v1
and v2)
Limitations
We measured strain rate and strain only in the
radial direction, because in closed-chest pigs only
parasternal views (and not apical views for longitudinal function) can be obtained.
Another limitation of the study is that we chose to
record data only from one sampling site in the posterior
wall. This was related to limitations in the current
data acquisition and postprocessing methodology: because of the angle dependency of strain rate, imaging
radial deformation in a closed-chest animal model can
only be calculated for the posterior wall and the interventricular septum. Because septal deformation can be
influenced by both LV and right ventricular function,
only the posterior wall was investigated. Accordingly,
our results show trends in the variations of radial
myocardial deformation in a normal myocardial segment during inotropic and chronotropic modulation
and cannot be directly extrapolated to all segments. In
a normal heart with only a small degree of regional and
temporal inhomogeneity, it can be expected that the
present results can be extrapolated to all regions and
strains, although this remains to be confirmed. In a
diseased heart, however, interactions between normal
and abnormal regions could have important effects
which can change the observed relations. Further studies on this subject in ischemic models and individuals
are thus warranted.
All Doppler techniques are angle dependent. This is
also applicable to myocardial Doppler velocities and
deformation indexes. This limitation was minimized in
this study by a careful alignment of the ultrasound
beam with the radial contraction of the posterior wall.
Another inherent limitation to regional CDMI indexes is the influence of global cardiac translation and
motion. Prior investigations have clearly shown the
translation dependency of myocardial velocities. Because strain rate computation is based on velocity
gradients (see APPENDIX), this translation dependency is
minimized as suggested by prior publications (24).
AJP-Heart Circ Physiol • VOL
SR ⫽
v1 ⫺ v2
L
with L reflecting the distance between points 1 and 2 (8).
When a segment thickens in the radial direction, SR is
defined to have a positive SR value. When a segment thins in
the radial direction, it is characterized by a negative value
(Fig. 1).
Strain
Regional ⑀ values can be obtained by integrating the regional SR curve over time. ⑀ defines the relative amount of
local deformation caused by an applied force (8). Myocardial
radial ⑀ increases during myocardial thickening and decreases during thinning. Both thickening and thinning can
be measured over time throughout the cardiac cycle. The
ultrasound technique, as currently formatted, estimates the
instantaneous change in segment length. This is the natural
⑀ value (⑀N) (8), which is expressed as a percentage, and is
described by the equation
t
兰
⑀ N ⫽ SRdt
t0
where t0 is a reference time point, t is the instant time point,
and dt is an infinitesimally small time interval.
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