© 1995 American Heart Association, Inc.
Articles |
Echocardiographic Assessment of Left Ventricular Mass and Systolic Function in Mice
From the Departments of Microbiology and Immunology (J.M.G., J.G.E., L.A.L.), Medicine (Cardiology) (J.M.G., F.M.S., R.N.K., L.A.L.), and Cell Biology (R.N.K.), Albert Einstein College of Medicine, Bronx, NY.
Correspondence to Julius M. Gardin, MD, Division of Cardiology, University of California Irvine Medical Center, 101 City Dr South, Rt 81, Bldg 53, Orange, CA 92668.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Abstract The increasing use of transgenic mouse models for investigating the mechanisms of cardiac growth and function has made it important to develop noninvasive methods for assessing murine cardiac anatomy, size, and function. At present, murine cardiac mass can be determined only at necropsy. Left ventricular (LV) function can be assessed by use of various catheterization techniques, but these approaches are usually terminal procedures and provide no information about chamber anatomy and dimensions. Although transthoracic echocardiography has been used to study the LVs of rats and larger animals, the considerably smaller LV masses and somewhat faster heart rates of mice pose significant challenges to obtaining good-quality echocardiograms. In this study we tested the hypothesis that transthoracic echocardiography can image the murine LV as well as provide assessments of LV mass and function. Our results in a series of 33 mice, including normal, transgenic, and aortic-banded subgroups, demonstrate the capability of transthoracic two-dimensionally directed M-mode echocardiography in mice to (1) obtain good-quality images, (2) produce estimates of LV mass having good correlations with directly determined LV mass in normal mice, (3) detect LV hypertrophy noninvasively in different experimental models, and (4) identify impaired LV systolic function. Thus, echocardiography appears to be a promising approach for noninvasively assessing LV mass and function in mice.
Key Words: echocardiography • mice • transgenics • left ventricular mass • left ventricular function
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Genetic perturbations are frequently used to investigate molecular aspects of cardiac growth and function. For the most part, these experiments are performed in the mouse because of the extent to which its genome has been characterized and because techniques have been developed to facilitate genetic manipulations in this species. For example, transgenic mice expressing c-myc1 2 and the simian virus 40 T antigen3 4 in fetal cardiac myocytes exhibit hyperplasia of these cells. These and other transgenic mouse models of cardiac growth and function have made it crucial to be able to assess murine cardiac anatomy, size, and function in a noninvasive manner. At present, weighing the heart at necropsy is the only way to assay murine cardiac mass, thereby precluding longitudinal studies in the same animal. Function of the murine left ventricle (LV) can be evaluated by catheterizing the LV in situ5 and in isolated perfused preparations.6 7 These approaches present technical problems, however, and are not easily repeated in the same animal. Moreover, they provide no information about chamber anatomy and dimensions. Clearly, it would be useful to have a noninvasive method that could be used to assess both LV size and function.
Transthoracic echocardiography has been used to assess LV mass and/or
function in cats,8 rabbits,9 10 11 12 and
rats.13 14 15 16 17 18 19 However, the mass of the mouse heart is only
1/10 that of the rat's, and the mouse's heart rate tends to be
significantly faster (400 to 700 beats per minute; Table 1
). In this study, we tested the hypothesis that
transthoracic two-dimensionally directed M-mode echocardiography can be
used to image the murine LV and can provide a means of assessing LV
mass and function. Our results demonstrate the technical feasibility of
obtaining good-quality echocardiograms in mice and the fact that
measurements from these can be used to estimate LV mass, detect LV
hypertrophy, and identify depressed LV systolic function.
|
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Murine Models
Several groups of mice were studied using transthoracic echocardiography. The first group consisted of 15 female wild-type CD-1 mice. The second group consisted of 15 FVB/NJ mice: 9 were hemizygous for a bovine myf 5 transgene (3 males and 6 females) and 6 were wild-type (4 males and 2 females). Myf 5 is a basic helix-loop-helix protein and is involved in skeletal myogenesis.20 In wild-type mice, its expression is restricted to fetal skeletal muscle and its precursors.21 In these transgenic mice, myf 5, driven by murine sarcoma virus long terminal repeat sequences, is expressed at high levels in heart and brain.22 The cardiac phenotype is characterized by an increase in LV mass of
20%, a 100% increase in left atrial
mass, and pulmonary edema in some animals at necropsy (J. Edwards, C.
Smith, L. Leinwand, unpublished data, 1994). Body masses ranged from
17.5 to 43.3 g in the CD-1 mice, from 21.0 to 38.5 g in the wild-type
FVB/NJ mice, and from 21.0 to 31.5 g in the myf 5 FVB/NJ
mice. A third group of mice was subjected to surgical constriction
(banding) of the abdominal aorta23 for 87 days as a test
of the accuracy and reliability of these echocardiographic estimates of
LV hypertrophy in an independent model. This group consisted of 3 CD-1
males: 1 wild-type and 2 that overexpressed the c-myc
transgene1 2 in cardiac myocytes. In the unbanded state,
the hearts of these transgenic mice have an LV mass 25% greater
than that of wild-type controls. We have previously shown that
c-myc transgenic and wild-type mice attain similar LV masses
after 87 days of aortic constriction (70% greater than those of
unbanded wild-type mice).24
Transthoracic Echocardiography
After body masses were determined, mice were anesthetized with
Avertin 2.5% (0.015 mL/g body mass IP).25 This was
supplemented with increments of 0.004 mL/g to maintain light
anesthesia. Mice were lightly secured in the supine position to a
warming pad, and the precordium was shaved. Transthoracic
echocardiography was performed by use of an Acuson XP-10 cardiac
ultrasound machine with a 7-MHz transducer, which had 128 imaging
elements configured in a phased-array format. The heart was first
imaged in the two-dimensional mode in the parasternal long-axis and/or
parasternal short-axis views. These views were used to position the
M-mode cursor perpendicular to the ventricular septum and LV posterior
wall, after which M-mode images were obtained. All measurements were
made on-line using an 11-in monitor.
All primary measurements were made from images captured on cine loops
at the time of the study by use of the analysis software
present on the echocardiography machine. For each study,
measurements were made from 
3 beats (mean±SEM, 5.7±0.2 beats;
range, 3 to 9 beats). This criterion resulted in the exclusion of one
study that contained only 2 beats. Measurements of ventricular septal
thickness (VST), LV internal dimension (LVID), and LV posterior wall
thickness (LVPW) were made from two-dimensionally directed M-mode
images of the LV in both systole and diastole by use of the leading
edge–to–leading edge convention adopted by the American Society of
Echocardiography.26 Electrocardiography was not used as a
frame of reference to designate end diastole because the rapid heart
rates of mice cause filling to continue beyond the time of the QRS
complex. Rather, diastolic measurements were made at the time of the
apparent maximal LV diastolic dimension. LV end-systolic dimension was
measured at the time of the most anterior systolic excursion of the LV
posterior wall. Values from all of the measured beats in a given animal
were then averaged. LV (minor axis) percent fractional shortening
(LV%FS), a measure of systolic function, was calculated as
 |
 |
Other Echocardiographic Approaches
An additional group of 8 mice, ranging in weight from 20 to 30
g, was studied by use of 3.5F or 5.0F intravascular ultrasound
catheters with 20-MHz multielement array transducers (Endosonics).
After anesthesia was administered as described above, the catheters
were used from multiple approaches: transesophageal; transjugular, from
both the right atrium and right ventricle; transperitoneal; and
open-chest, both from the LV epicardial surface and through direct LV
puncture.
Necropsy
After echocardiography, an additional 0.6 mg/g Avertin was
administered intraperitoneally, after which the heart and lungs were
removed. By use of a x40 dissecting microscope, the LV (with
ventricular septum), right ventricle, and lungs were quickly dissected,
blotted, and weighed without fixation on a Sartorius model 1207-MP2
analytical balance.
Statistics
Relations between parameters were evaluated by least-squares
linear regression analysis. Group means were compared by Student's
t test. Statistical power analysis was used to estimate
the minimum detectable differences between group means.28
Differences at the P<.05 level were considered
significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
High-Quality Ultrasound Images of the Mouse Heart Can Be Obtained
We assessed the technical feasibility of obtaining good-quality echocardiograms in mice, given the small size of the murine heart (1/10 that of the rat). Using intravascular ultrasound catheters with 20-MHz multielement array transducers, we attempted to image the hearts of 20- to 30-g mice from multiple approaches. Depth of field (4 mm) was insufficient to visualize the entire LV in cross section from the transesophageal and transjugular (with the probe in the right atrium or right ventricle) approaches. Transperitoneal and open-chest epicardial approaches yielded poor images because of inadequate depth of field and/or the relatively small sector angles subtended by the imaging elements. With the transducer positioned within the LV through direct LV puncture, the epicardium could be imaged satisfactorily, but the endocardium was poorly seen, probably because it was within the 1.9-mm "ringdown" artifact. In addition, all of these approaches lacked sufficient temporal resolution to provide images from which LV function could be assessed, because the transducers were only capable of imaging at a rate of 10 frames per second. Thus, we were unable to obtain good-quality murine echocardiograms with these high-frequency intravascular ultrasound catheters.
In contrast, by use of a 7-MHz 128-element transducer with an Acuson
XP-10 ultrasound machine, fair-quality transthoracic two-dimensional
echocardiographic images of the LV could be obtained. These images,
however, were of insufficient quality to define LV wall motion at
discrete points in the cardiac cycle. This was due, in part, to the
rapidity of heart rate in the mouse, from 400 to 700 beats per minute
(6 to 12 beats per second), relative to the maximum rate at which
two-dimensional images could be resolved (30 frames per second). In
addition, the spatial resolution provided by two-dimensional imaging
was suboptimal. To improve both temporal and spatial resolution, the
heart was examined by M-mode echocardiography using
twodimensional images in the parasternal long- or short-axis
views to position the M-mode cursor. Fig 1 (top) shows
an example of an M-mode echocardiogram from a 34-g mouse. The LV
posterior wall is clearly defined; its position oscillates at a
frequency of 480 cycles per minute, reflecting the heart rate. In
addition, a distinct variation in this "picket fence" appearance
is seen with every third beat, corresponding to the observed
respiratory rate of 160/min. Of note, although the ventricular septum
can be identified, its image is not as clear as that of the LV
posterior wall, a finding noted in most of the mice studied. To
determine whether size would preclude obtaining an adequate
echocardiographic examination in very small mice, we studied a 12.5-g
animal. As can be seen in Fig 1 (bottom), it was possible to image even
this LV, which weighed 42.8 mg at autopsy. The echocardiographically
determined diastolic LVID and LVPW were 1.3 and 0.7 mm, respectively.
These experiments demonstrate that good-quality M-mode echocardiograms
can be obtained in mice of sizes ranging from 12.5 to 44.0 g.
|
Murine LV Mass Can Be Assessed Reliably by Noninvasive
Echocardiography
LV mass can be predicted from echocardiographic measurements in
humans and other animals by use of a variety of formulas that make
various assumptions about chamber geometry.29 We wished to
determine whether LV mass could be predicted reliably from
echocardiographic measurements in mice by use of the uncorrected cube
formula described above. Fifteen female CD-1 mice with body weights
ranging from 17.5 to 43.5 g underwent two-dimensionally directed M-mode
echocardiograms, after which the animals were killed and the LV masses
measured directly. Primary echocardiographic measurements are shown in
Table 1
. LVID in diastole ranged from 1.7 to 2.5 mm, and the diastolic
VST and LVPW were between 0.7 and 0.9 mm. LV mass estimates were
calculated from these primary measurements and then plotted versus
directly measured LV mass (Fig 2). The linear regression
through these data points is represented by the solid line
(y=0.36x+9.07; r=.87,
P<.0001, standard error of estimate=5.88 mg). To extend the
range of measurements, three additional points representing the
hypertrophied LVs of aortic-banded mice are included. The dashed line
represents the linear regression through all data points in
this figure (y=0.40x+6.20;
r=.96, P<.0001, standard error of estimate=6.45
mg). Thus, echocardiographically derived LV mass estimates are linearly
related to actual LV masses over a very broad range. Of note, the
absolute values of echocardiographically determined LV masses are
systematically lower than those of actual LV masses (see
"Discussion"). Nevertheless, the good correlation between these
parameters demonstrates that murine LV mass can be estimated
noninvasively from echocardiographic measurements.
|
) are
significantly correlated (r=.87, P<.0001). The
linear regression through these data (solid line) is defined by the
equation y=0.36x+9.07, where x and
y denote LV mass determined at necropsy and
echocardiographically, respectively. Data for 3 mice subjected to
abdominal aortic constriction (1 wild-type mouse [
] and 2 mice
overexpressing the c-myc transgene [
]) are also
included. The linear regression through all data points (dashed line:
y=0.40x+6.20, r=.96) is similar to
that for the 15 normal animals alone (solid line).
Murine LV Mass Can Be Determined Echocardiographically in Different
Models of LV Hypertrophy
In the absence of genetic, surgical, or pharmacological
interventions, the relation between LV mass and body mass of mammals is
highly predictable. For example, gravimetrically measured LV mass
correlates very closely (r=.98, P<.0001) with
body mass in the group of mice reported in Fig 2 (data not shown).
Thus, for normal CD-1 females, LV mass can be predicted quite
accurately from body mass, and abnormal LV growth defined in relation
to these predictions. LV hypertrophy can be induced by a variety of
experimental means and generally develops over a period of days to
weeks. Without some noninvasive means of tracking this progression, the
only way to follow these changes is by euthanatizing animals at
intervals after the onset of the experimental procedure. This is very
expensive and time-consuming and precludes following the unique
sequence of changes in any single animal. The above data on normal mice
suggest that transthoracic two-dimensionally directed M-mode
echocardiography has sufficient resolution to follow reliably the
changes in LV mass associated with normal growth (the wide range of
body masses reflects a comparably wide range of ages). However, it is
possible that specific geometric alterations associated with various
forms of LV hypertrophy could cause the relation shown in Fig 2 to
become nonlinear. For this reason, it is important to assess the
validity of echocardiography to determine changes in murine LV mass in
different models of LV hypertrophy.
To test whether echocardiographically and directly determined LV mass correlate closely in hypertrophic hearts, we first compared the hearts of mice hemizygous for a bovine myf 5 transgene with those of nontransgenic mice of the same strain (FVB/NJ). In contrast to wild-type mice, in which the endogenous myf 5 gene is expressed solely in fetal skeletal muscle and its precursors,21 these transgenic mice express high levels of bovine Myf 5 in cardiac muscle and brain.22 The phenotype manifests itself in the heart by increases in LV and left atrial masses and pulmonary edema (J. Edwards, C. Smith, L. Leinwand, unpublished data, 1994). We performed two-dimensionally directed M-mode studies on 9 myf 5 transgenic mice (3 males and 6 females; body mass, 26±4 g [mean±SEM]) and 6 wild-type littermates (4 males and 2 females; mean body mass, 31±7 g). Subsequently, the animals were killed, and LV mass was determined. The ratios of directly measured LV mass to body mass (3.06±0.05 mg/g for wild-type mice and 3.67±0.14 mg/g for transgenic mice) are significantly different (P<.01), representing a mean LV hypertrophy of 20% in the myf 5 mice.
The relation between directly measured LV mass and body mass for these
two groups of animals is shown in Fig 3 (top). LV mass
and body mass are closely correlated within the individual groups
(r=.88, P<.01, for transgenic mice;
r=.99, P<.001, for wild-type mice), but these
lines differ greatly in slope (4.87 versus 2.66) and y
intercept (-31.14 versus 12.00). These data illustrate that LV mass
for most of the transgenic mice exceeds that predicted by the LV
mass–to–body mass regression for wild-type mice. In contrast, as
shown in Fig 3 (bottom), the regression lines that define the relations
between echocardiographically and directly determined LV mass in
transgenic and wild-type groups are almost identical (slopes, 0.60 and
0.58; y intercepts, -11.24 and -8.93, respectively, for
transgenic and wild-type mice). Thus, echocardiography is able to
predict relative LV mass reasonably accurately in this model of LV
hypertrophy.
|
). Top, Actual LV mass (y)
versus body mass (x). Equations for regression lines are
y=4.87x-31.14 (r=.88,
P<.01) for transgenic mice (solid line) and
y=2.66x+12.00 (r=.99,
P<.0001) for control mice (dashed line). Bottom,
Echocardiographically determined LV mass (y) versus actual
LV mass (x). Equations for regression lines are
y+0.60x-11.24 (r=.91,
P<.001) for transgenic mice (solid line) and
y=0.58x-8.93 (r=.77,
P=.07) for control mice (dashed line). For both groups
combined, values are r=.87, P<.0001.
The increase in LV mass in myf 5 transgenic mice was the
result of increases in LVID, VST, and LVPW, although only the latter
achieved statistical significance (Fig 4A [left]). Of
note, the degree of hypertrophy detected echocardiographically in this
model (25%, Fig 4A [right]) was similar to that detected
gravimetrically at necropsy (20%). To test the ability of
echocardiography to predict LV mass in hypertrophied but nondilated
hearts, we examined another model of hypertrophy. Three additional mice
(body mass, 37±1 g) were subjected to surgical constriction of the
abdominal aorta, a model that in rats produces echocardiographic
evidence of concentric LV hypertrophy.19 These hearts were
compared with those from 8 weight-matched controls whose data appear in
Table 1 (body masses30 g; mean±SEM: 37±2 g). Directly determined LV
mass at autopsy was 200±20 mg in the aortic-banded mice and 111±12 mg
in the control mice (P<.05), indicating mean LV hypertrophy
of 80%. Echocardiographically estimated LV mass was likewise 80%
greater in the aortic-banded mice, whether expressed in absolute terms
(88±7 versus 49±3 mg, respectively) or in relative terms (Fig 4B
[right]). In contrast to the myf 5 mice, the increase in
LV mass in aortic-constricted mice resulted from marked increases in
both septal thickness and posterior wall thickness, without any
evidence of LV chamber dilatation (Fig 4B [left]). In addition,
despite this major difference in LV geometry, data for the 3
aortic-banded mice fall on the linear regression line for normal mice
(Fig 2). Thus, LV mass in hypertrophied nondilated hearts can be
quantified by use of echocardiography.
|
Minimum Detectable Differences in LV Mass
One of the potential applications of echocardiography in mice is
for noninvasive assessment of LV mass serially in the same animal or
between groups of animals. No serial measurements were made in the
present study. However, the minimum detectable difference in mean
LV mass between groups of animals can be estimated by statistical power
analysis28 from the relations between
echocardiographically and directly determined LV mass for
myf 5 and wild-type mice (Fig 3 [bottom]). If one accepts
probabilities of type I and type II errors of 5% and 10%,
respectively, an increment in LV mass of 18.5% can be detected when
each group contains 10 animals. With groups of 15 or 20 animals each,
the minimum detectable increments are 14.5% and 12.7%, respectively.
Therefore, our findings suggest that the magnitude of increase in LV
mass observed in many models of hypertrophy could be detected
echocardiographically.
Depressed LV Systolic Function Can Be Identified
Echocardiographically in Mice
As a first step toward assessing the ability of
echocardiography to evaluate murine LV systolic function, we
compared echocardiographically determined LV%FS (minor axis) in normal
mice and in mice with pulmonary edema (Table 2). LV%FS
was 55.7±1.4% (mean±SEM) in 6 FVB/NJ wild-type mice. This was
similar to the 57.7±0.8% measured in the 15 wild-type CD-1 mice
reported in Table 1 (P=NS; data not shown).
|
A subset of myf 5 transgenic mice exhibit labored breathing
and lethargy and have markedly edematous lungs at necropsy (J. Edwards,
C. Smith, L. Leinwand, unpublished data, 1994). We hypothesized that
these characteristics result from LV systolic dysfunction. Among the
group of 9 myf 5 transgenic mice, only 3 of which manifested
pulmonary edema at necropsy, LV%FS was mildly depressed (46.3±4.1%),
but the difference from wild-type FVB/NJ control mice was not
statistically significant. However, LV%FS was inversely correlated
with the ratio of lung mass to body mass, a quantitative index of the
degree of pulmonary edema (r=-.79, P<.0005). In
particular, 6 of 6 wild-type and 6 of 9 myf 5 mice exhibited
LV%FS in the 50% to 61% range and lung mass–to–body mass ratios
within 2 SD of the wild-type mean of 6.53 mg/g. In contrast, 3
myf 5 mice (animals 13, 14, and 15 in Table 2) exhibited
LV%FS of 38%, 31%, and 24% and lung mass–to–body mass ratios of
10.6, 7.8, and 16.9 mg/g, respectively. Thus, markedly depressed LV%FS
was detected echocardiographically in animals 13 and 15, which clearly
manifested pulmonary edema as indicated by markedly elevated lung
mass–to–body mass ratios. Animal 14 had a depressed LV%FS but a
normal lung mass–to–body mass ratio. Whether decreased LV%FS
reflects poor LV function in an animal that has not yet developed
pulmonary edema or an incorrect echocardiographic measurement in a
mouse with normal systolic function cannot be determined from the above
data. Direct comparisons with other standards of LV function (eg,
dP/dt) are required to differentiate these possibilities. These data
suggest, however, that severely depressed LV systolic function in mice
can be identified echocardiographically. An example of a murine
echocardiogram demonstrating poor LV systolic function is provided by
the study of animal 15, whose LV%FS was 24% (Fig 5,
middle). Note the poor excursions of the ventricular
septum and LV posterior wall. In contrast, these structures can be seen
to move well in the echocardiogram of wild-type animal 2, whose LV%FS
was 58% (Fig 5, bottom).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
These data demonstrate that good-quality two-dimensionally directed M-mode echocardiograms can be obtained in mice. Measurements from these echocardiograms can be used with the uncorrected cube formula to estimate percentage changes in LV mass reliably in both normal mice and mice with LV hypertrophy. Our data suggest that group differences in mean LV mass of
15% can be resolved with a sample
size of 15 for each group. Thus, echocardiography appears to provide a
viable noninvasive means of assessing the effects of surgical,
pharmacological, and genetic interventions on cardiac growth in mice
over time. In the present study, the correlation coefficients for the relation between murine LV mass determined echocardiographically and that measured directly at necropsy ranged from .87 to .96. These are similar to the correlation coefficients of .87 to .94 reported previously in rats.13 14 19 30 The validity of using this relation to track relative changes in LV dimensions and mass is confirmed by the ability of the echocardiographic measurements to detect LV hypertrophy in two very different experimental models: transgenic mice with hypertrophied cardiomegalic hearts and a surgical model of LV hypertrophy without dilatation. This was a major goal of the present study. Of note, however, there is an appreciable discrepancy between the echocardiographic and postmortem determinations of LV mass that is not seen in studies of larger mammals (eg, rats and rabbits).
One potential source of this discrepancy is the choice of algorithm for conversion of the M-mode measurements into estimates of LV mass. The uncorrected cube formula models the LV as a shell of tissue between two prolate ellipsoids, each having a long axis–to–short axis ratio of 2:1,12 19 which is close to that of the normal human LV chamber31 but clearly greater than its external long axis–to–short axis ratio.32 This feature of the formula favors overestimation of LV mass, as was found in echocardiographic studies of the dog LV33 and of the human LV.34 Moreover, LV long axis–to–short axis ratios do not seem to be any greater in most other mammals,35 including the mouse.36 Thus, although there are undoubtedly more accurate algorithms, it does not appear that LV mass was underestimated in these mice by use of the uncorrected cube formula.
Other sources of this discrepancy include difficulty in directing the M-mode axis to the widest part of the LV in these small hearts and the possibility that the mouse LV may have a shorter anterior wall–to–posterior wall minor axis (close to the probe's orientation) compared with its septum-to–lateral wall minor axis. Furthermore, although care was taken to apply minimal pressure of the transducer to each mouse's chest, we cannot exclude the possibility that this pressure may have produced some deformation of the beating heart, possibly contributing to the unexpectedly low absolute values of our dimension measurements. Further studies will be needed to resolve the source of the discrepancy between absolute values of LV mass determined echocardiographically and those determined gravimetrically. Of interest, another group of investigators has recently reported absolute values in normal mice of LVID and LVPW determined by transthoracic echocardiography37 that are similar to those in the present study. This suggests that the discrepancy between actual LV mass and echocardiographically estimated LV mass did not result from interobserver variability. Although this issue has not yet been resolved, it should be addressable, and its resolution may lead to improvements in the accuracy of noninvasive echocardiographic measurements of the murine heart in absolute terms. Despite this limitation with respect to absolute measurements, this technique in its present form offers a reliable means of noninvasively assessing changes or differences in LV mass and dimensions in mice.
The present study found fractional shortening in normal mice to be
57%, which is similar to that in normal rats
(61%13 19 ) and higher than that in normal rabbits
(35%9 10 11 ) and in normal humans
(36%38 39 ). These interspecies differences may be
attributable to the greater ratio of LV wall thickness (sum of VST and
LVPW) to LVID in mice (0.80 in this study) and rats
(0.5017 ) compared with that in rabbits
(0.3011 ) and humans (0.3340 ). Work by
de Simone et al17 indicated that a single inverse relation
between LV systolic wall stress and LV fractional shortening could
describe data from normotensive rats and humans, suggesting that the
greater LV fractional shortening seen in small rodents may be a
consequence of reduced contractile element load. These anatomic and
functional differences between species may also be related to the
distribution of myosin heavy chain isoforms, which are predominantly of
the V1 isoform in mice and rats and of the V3
isoform in rabbits and humans.41 Although the data
presented here for myf 5 transgenic mice suggest that
severely depressed LV systolic function can be identified
echocardiographically, further work is needed to validate these
measurements.
An important limitation of the echocardiographic approach used in the
present study is that measurements were obtained from
two-dimensionally directed M-mode studies, which provide only an
"ice pick" view of the heart rather than a two- or
three-dimensional perspective. With currently available equipment,
two-dimensional images of sufficient temporal and spatial
resolution could not be obtained to allow accurate determination of
LV dimensions and wall thicknesses in the mouse heart. In contrast,
these parameters could be measured at defined points in the cardiac
cycle using a two-dimensionally directed M-mode approach, because this
method provides a much higher sampling rate (1000 samples per
second) than can be obtained when two-dimensional images are acquired
in real time (33 frames per second). A corollary of this limitation is
that the approach used here may not be applicable to some murine
models, such as animals with LV segmental wall motion abnormalities
(eg, ischemic heart disease) or with nonhomogeneous distributions of LV
hypertrophy.
In summary, good-quality transthoracic two-dimensionally guided M-mode echocardiograms can be obtained in mice and used to noninvasively track changes in LV mass and systolic function in disease models. Although further investigation is needed to validate measurements of LV systolic function, to improve the accuracy of the echocardiographic measurements in absolute terms, and to determine the general applicability of this approach to various other models of cardiac disease, the present study demonstrates that echocardiography constitutes a promising approach to the noninvasive assessment of LV mass and function in mice.
Note added in proof. Following initial submission of this manuscript, a report by Manning et al demonstrated echocardiographic assessment of LV mass in mice. (Am J Physiol. 1994;266(Heart Circ Physiol35):H1672-H1675.)
|
Acknowledgments |
|---|
This study was partially supported by a National Institutes of Health (NIH) National Research Service Award–Senior Fellowship for sabbatical research (to Dr Gardin), grants from the NIH (HL-50560 to Dr Leinwand and HL-02699 to Dr Kitsis), and by the loan of cardiac ultrasound equipment from the Acuson Corporation. Dr Kitsis is the Charles and Tamara Krasne Faculty Scholar in Cardiovascular Research.
Received March 25, 1994; accepted December 10, 1994.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Swain JL, Stewart TA, Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell. 1987;50:719-727. [Medline] [Order article via Infotrieve]
2.
Jackson T, Allard MF, Spreenan CM, Doss LK, Bishop SP,
Swain JL. The c-myc proto-oncogene regulates cardiac
development in transgenic mice. Mol Cell Biol. 1990;10:3709-3716.
3.
Field LJ. Atrial natriuretic factor-SV 40
T-antigen transgenes produce tumors and cardiac arrhythmias in
mice. Science. 1988;239:1029-1033.
4.
Katz EB, Steinhelper ME, Delcarpio JB, Daud AI,
Claycomb WC, Field LJ. Cardiomyocyte proliferation in mice
expressing 
-cardiac myosin heavy chain-SV 40 T-antigen
transgenes. Am J Physiol. 1992;262:H1867-H1876.
5.
Rockman HA, Ross RS, Harris AN, Knowlton KU,
Steinhelper ME, Field LJ, Ross J Jr, Chien KR. Segregation of
atrial-specific and inducible expression of an atrial natriuretic
factor transgene in an in vivo murine model of cardiac
hypertrophy. Proc Natl Acad Sci U S A. 1991;88:8277-8281.
6. Ng WA, Grupp IL, Subramanian A, Robbins J. Cardiac myosin heavy chain mRNA expression and myocardial function in the mouse heart. Circ Res. 1991;69:1742-1750.
7. Grupp IL, Subramanian A, Hewett TE, Robbins J, Grupp G. Comparison of normal, hypodynamic, and hyperdynamic mouse hearts using isolated work-performing heart preparations. Am J Physiol. 1993;265:H1404-H1410.
8.
Pollack PS, Bailey BA, Budjak R, Fernandez E, Houser
SR. Progressive feline pressure overload: non-invasive
assessment correlates with abnormalities in single
cells. Am J Physiol. 1993;264:H1307-H1314.
9. Magid NM, Young MS, Wallerson DC, Goldweit RS, Carter JN, Devereux RB, Borer JS. Hypertrophic and functional response to experimental chronic aortic regurgitation. J Mol Cell Cardiol. 1988;20:239-246. [Medline] [Order article via Infotrieve]
10. DeFelice A, Fein S, Daudiss K, Frering R, Horan P. Beneficial hemodynamic effects of milrinone in conscious rabbits with chronic aortic regurgitation. J Cardiovasc Pharmacol. 1989;14:659-665. [Medline] [Order article via Infotrieve]
11.
Magid NM, Wallerson DC, Borer JS, Mukherjee A, Young
MS, Devereux RB, Carter JN. Left ventricular diastolic and
systolic performance during chronic experimental aortic
regurgitation. Am J Physiol. 1992;263:H226-H233.
12. Young MS, Magid NM, Wallerson DC, Goldweit RS, Devereux RB, Carter JN, Im JY, Hall MA, Borer JS. Echocardiographic left ventricular mass measurements in small animals: anatomic validation in normal and aortic regurgitant rabbits. Am J Noninv Cardiol. 1990;4:145-153.
13. de Simone G, Wallerson DC, Volpe M, Devereux RB. Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats: necropsy validation. Am J Hypertens. 1990;3:688-696. [Medline] [Order article via Infotrieve]
14. Nakamura T, Shimoo K, Kuribayashi T, Matsubara K, Shima M, Matsumoro A, Azuma A, Katsume H, Nakagawa M. Visualization of the heart and determination of left ventricular mass in rats by echocardiography. Jpn Heart J. 1991;32:481-491. [Medline] [Order article via Infotrieve]
15.
Litwin SE, Katz LE, Morgan JP, Douglas PS.
Serial echocardiographic assessment of left ventricular geometry
and function after large myocardial infarction in the rat.
Circulation. 1994;89:345-354.
16.
de Simone G, Devereux RB, Camargo MJF, Wallerson DC,
Laragh JH. Influence of sodium intake on in-vivo left
ventricular anatomy in experimental renovascular
hypertension. Am J Physiol. 1993;264:H2103-H2110.
17. de Simone G, Devereux RB, Volpe M, Camargo MJF, Wallerson DC, Laragh JH. Relation of left ventricular hypertrophy, afterload and contractility to left ventricular performance in Goldblatt hypertension. Am J Hypertens. 1992;5:292-301. [Medline] [Order article via Infotrieve]
18. de Simone G, Devereux RB, Camargo MJF, Volpe M, Wallerson DC, Atlas SA, Laragh JH. In-vivo left ventricular anatomy in rats with two-kidney, one-clip and one-kidney, one-clip renovascular hypertension. J Hypertens. 1992;10:725-732. [Medline] [Order article via Infotrieve]
19.
Pawlush DG, Moore RL, Musch TI, Davidson WR.
Echocardiographic evaluation of size, function, and mass of
normal and hypertrophied rat ventricles. J Appl
Physiol. 1993;74:2598-2605.
20. Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH. A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J. 1989;8:701-709. [Medline] [Order article via Infotrieve]
21.
Ott MO, Bober E, Lyons G, Arnold H, Buckingham M.
Early expression of the myogenic regulatory gene,
myf-5, in precursor cells of skeletal muscle in the mouse
embryo. Development. 1991;111:1097-1107.
22.
Santerre RF, Bales KR, Janney MJ, Hannon K, Fisher LF,
Bailey CS, Morris J, Ivarie R, Smith CK II. Expression of bovine
myf5 induces ectopic skeletal muscle formation in transgenic
mice. Mol Cell Biol. 1993;13:6044-6051.
23. Siri FM. Chronic norepinephrine infusion and adrenergic function of hypertrophied hearts. Am J Physiol. 1983;248:H485-H492.
24. Kitsis RN, Siri FM, Lee S-J, Malhotra A, Gardin JM, Swain JL, Leinwand LA. Cardiac growth in aortic constricted c-myc transgenic mice. Circulation. 1993;88(suppl I):I-281. Abstract.
25. Hogan B, Constantini F, Lacy E. Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory; 1986.
26.
Sahn DJ, DeMaria A, Kisslo J, Weyman A, for the
Committee on M-Mode Standardization of the American Society of
Echocardiography. Recommendations regarding quantitation in
M-mode echocardiography: results of a survey of echocardiographic
methods. Circulation. 1978;58:1072-1083.
27.
Pombo JF, Troy BL, Russell RO Jr. Left
ventricular volumes and ejection fraction by
echocardiography. Circulation. 1971;43:480-490.
28. Zar JH. Biostatistical Analysis. Englewood Cliffs, NJ: Prentice Hall; 1984.
29. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Shan D, Schnittger I, Silvermann N, Tajik AJ. Recommendation for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989;2:358-367. [Medline] [Order article via Infotrieve]
30. Jones EF, Harrap SB, Calafiore P, Tonkin AM. Development and validation of echocardiographic methods for estimation of left ventricular mass in rats. Clin Exp Pharmacol Physiol. 1992;19:361-364. [Medline] [Order article via Infotrieve]
31. Hutchins GM, Bulkley BH, Moore GW, Piasio MA, Lohr FT. Shape of the human cardiac ventricles. Am J Cardiol. 1978;41:646-654. [Medline] [Order article via Infotrieve]
32. Zile MR, Tanaka R, Lindroth JR, Spinale F, Carabello BA, Mirsky I. Left ventricular volume determined echocardiographically by assuming a constant left ventricular epicardial long-axis/short-axis dimension ratio throughout the cardiac cycle. J Am Coll Cardiol. 1992;20:986-993. [Abstract]
33.
Wyatt HL, Heng MK, Meerbaum S, Hestenes JD, Cobo JM,
Davidson RM, Corday E. Cross-sectional echocardiography, I:
analysis of mathematical models for quantifying mass of the left
ventricle in dogs. Circulation. 1979;60:1104-1113.
34. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450-458. [Medline] [Order article via Infotrieve]
35.
Lee JC, Taylor JFN, Downing SE. A comparison of
ventricular weights and geometry in newborn, young, and adult
mammals. J Appl Physiol. 1975;38:147-150.
36.
Vornanen M. Basic functional properties of the
cardiac muscle of the common shrew (Sorex araneus) and some
other small mammals. J Exp Biol. 1989;145:339-351.
37. Hartley CJ, Michael LH, Johnston AL. High resolution echocardiography in mice. Circulation. 1993;88(suppl I):I-276. Abstract.
38. Gardin JM, Henry WL, Savage DD, Ware JH, Burn C, Borer JS. Echocardiographic measurements in normal subjects: evaluation of an adult population without clinically apparent heart disease. J Clin Ultrasound. 1979;7:437-447.
39.
Henry WL, Gardin JM, Ware JH. Echocardiographic
measurements in normal subjects from infancy to old age.
Circulation. 1980;62:1054-1061.
40. Gaasch WH. Left ventricular radius to wall thickness ratio. Am J Cardiol. 1979;43:1189-1194. [Medline] [Order article via Infotrieve]
41. Nadal-Ginard B, Mahdavi V. Molecular basis of cardiac performance: plasticity of the myocardium generated through protein isoform switches. J Clin Invest. 1989;84:1693-1700.
This article has been cited by other articles:
 |
|
 |
|
  T. A. Doser, S. Turdi, D. P. Thomas, P. N. Epstein, S.-Y. Li, and J. Ren Transgenic Overexpression of Aldehyde Dehydrogenase-2 Rescues Chronic Alcohol Intake-Induced Myocardial Hypertrophy and Contractile Dysfunction Circulation, April 14, 2009; 119(14): 1941 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Derumeaux, F. Ichinose, M. J. Raher, J. G. Morgan, T. Coman, C. Lee, J. M. Cuesta, H. Thibault, K. D. Bloch, M. H. Picard, et al. Myocardial Alterations in Senescent Mice and Effect of Exercise Training: A Strain Rate Imaging Study Circ Cardiovasc Imaging, November 1, 2008; 1(3): 227 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. X. Fang, F. Dong, D. P. Thomas, H. Ma, L. He, and J. Ren Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1206 - H1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Hinton Jr., C. M. Alfieri, S. A. Witt, B. J. Glascock, P. R. Khoury, D. W. Benson, and K. E. Yutzey Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2480 - H2488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ren, J. Duan, D. P. Thomas, X. Yang, N. Sreejayan, J. R. Sowers, A. Leri, J. Kajstura, F. Gao, and P. Anversa IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R793 - R802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Dong, Q. Li, N. Sreejayan, J. M. Nunn, and J. Ren Metallothionein Prevents High-Fat Diet Induced Cardiac Contractile Dysfunction: Role of Peroxisome Proliferator Activated Receptor {gamma} Coactivator 1{alpha} and Mitochondrial Biogenesis Diabetes, September 1, 2007; 56(9): 2201 - 2212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Krishnamurthy, V Subramanian, M Singh, and K Singh Deficiency of {beta}1 integrins results in increased myocardial dysfunction after myocardial infarction Heart, September 1, 2006; 92(9): 1309 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Saraste, V. Kyto, M. Saraste, T. Vuorinen, J. Hartiala, and P. Saukko Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H871 - H875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, W. Tan, A. B. Stein, B. Dawn, W.-J. Wu, X. Zhu, X. Lu, X. Xu, T. Siddiqui, et al. Gene therapy with iNOS provides long-term protection against myocardial infarction without adverse functional consequences Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H584 - H589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Walker Jr., M. S. Nillas, E. I. Mangiarua, S. Cansino, R. G. Morrison, R. R. Perdue, W. E Triest, G. L. Wright, M. Studeny, P. Wehner, et al. Age-Associated Changes in Hearts of Male Fischer 344/Brown Norway F1 Rats Ann. Clin. Lab. Sci., January 1, 2006; 36(4): 427 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ohlmann, A. Tesse, C. Loichot, H. R. Ranaivo, G. Roul, C. Philippe, D. M. Watterson, J. Haiech, and R. Andriantsitohaina Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2342 - H2349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. B Popovic, J. P. Sun, H. Yamada, J. Drinko, K. Mauer, N. L Greenberg, Y. Cheng, C. S Moravec, M. S Penn, T. N Mazgalev, et al. Differences in left ventricular long-axis function from mice to humans follow allometric scaling to ventricular size J. Physiol., October 1, 2005; 568(1): 255 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Karackattu, M. H. Picard, and M. Krieger Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 803 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. M.C. Salemi, A. M.B. Bilate, F. J.A. Ramires, M. H. Picard, D. M. Gregio, J. Kalil, E. C. Neto, and C. Mady Reference values from M-mode and Doppler echocardiography for normal Syrian hamsters Eur J Echocardiogr, January 1, 2005; 6(1): 41 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dawson, C. A. Lygate, J. Saunders, J. E. Schneider, X. Ye, K. Hulbert, J. A. Noble, and S. Neubauer Quantitative 3-Dimensional Echocardiography for Accurate and Rapid Cardiac Phenotype Characterization in Mice Circulation, September 21, 2004; 110(12): 1632 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Seznec, D. Simon, L. Monassier, P. Criqui-Filipe, A. Gansmuller, P. Rustin, M. Koenig, and H. Puccio Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia Hum. Mol. Genet., May 15, 2004; 13(10): 1017 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Bale, M. Hoshijima, Y. Gu, N. Dalton, K. R. Anderson, K.-F. Lee, J. Rivier, K. R. Chien, W. W. Vale, and K. L. Peterson The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure PNAS, March 9, 2004; 101(10): 3697 - 3702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Woldbaek, T. A. Stromme, J. B. Sande, G. Christensen, T. Tonnessen, and A. Ilebekk Evaluation of a new fiber-optic pressure recording system for cardiovascular measurements in mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2233 - H2239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chalothorn, D. F. McCune, S. E. Edelmann, K. Tobita, B. B. Keller, R. D. Lasley, D. M. Perez, A. Tanoue, G. Tsujimoto, G. R. Post, et al. Differential Cardiovascular Regulatory Activities of the {alpha}1B- and {alpha}1D-Adrenoceptor Subtypes J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1045 - 1053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bernstein Exercise assessment of transgenic models of human cardiovascular disease Physiol Genomics, May 13, 2003; 13(3): 217 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Collins, C. E. Korcarz, and R. M. Lang Use of echocardiography for the phenotypic assessment of genetically altered mice Physiol Genomics, May 13, 2003; 13(3): 227 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. J. M. Creemers, J. N. Davis, A. M. Parkhurst, P. Leenders, K. B. Dowdy, E. Hapke, A. M. Hauet, P. G. Escobar, J. P. M. Cleutjens, J. F. M. Smits, et al. Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H364 - H371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Semeniuk, A. J. Kryski, and D. L. Severson Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H976 - H982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Wu, J. Hagaman, S. Kim, R. L. Reddick, and N. Maeda Aortic Constriction Exacerbates Atherosclerosis and Induces Cardiac Dysfunction in Mice Lacking Apolipoprotein E Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 469 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Y. T. Hart, J. C. Burnett Jr., and M. M. Redfield Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H1938 - H1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Collins, C. E. Korcarz, S. G. Shroff, J. E. Bednarz, R. C. Fentzke, H. Lin, J. M. Leiden, and R. M. Lang Accuracy of echocardiographic estimates of left ventricular mass in mice Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H1954 - H1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takuma, K. Suehiro, C. Cardinale, T. Hozumi, H. Yano, J. Shimizu, S. Mullis-Jansson, R. Sciacca, J. Wang, D. Burkhoff, et al. Anesthetic inhibition in ischemic and nonischemic murine heart: comparison with conscious echocardiographic approach Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2364 - H2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Suehiro, S. Takuma, C. Cardinale, T. Hozumi, J. Shimizu, H. Yano, M. R. Di Tullio, J. Wang, C. R. Smith, D. Burkhoff, et al. Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1729 - H1735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Wiesmann, J. Ruff, S. Engelhardt, L. Hein, C. Dienesch, A. Leupold, R. Illinger, A. Frydrychowicz, K.-H. Hiller, E. Rommel, et al. Dobutamine-Stress Magnetic Resonance Microimaging in Mice : Acute Changes of Cardiac Geometry and Function in Normal and Failing Murine Hearts Circ. Res., March 30, 2001; 88(6): 563 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Feldman, J. M. Erikson, Y. Mao, C. E. Korcarz, R. M. Lang, and G. L. Freeman Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1698 - H1707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rao and A. S. Verkman Analysis of organ physiology in transgenic mice Am J Physiol Cell Physiol, July 1, 2000; 279(1): C1 - C18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Spencer, K. Collins, C. Korcarz, R. Fentzke, R. M. Lang, and J. M. Leiden Effects of exercise training on LV performance and mortality in a murine model of dilated cardiomyopathy Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H210 - H215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Weig, K.-L. Laugwitz, A. Moretti, K. Kronsbein, C. Stadele, S. Bruning, M. Seyfarth, T. Brill, A. Schomig, and M. Ungerer Enhanced Cardiac Contractility After Gene Transfer of V2 Vasopressin Receptors In Vivo by Ultrasound-Guided Injection or Transcoronary Delivery Circulation, April 4, 2000; 101(13): 1578 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Henson, S. K. Song, J. S. Pastorek, J. J. H. Ackerman, and C. H. Lorenz Left ventricular torsion is equal in mice and humans Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1117 - H1123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-M. Gao, A. M Dart, E. Dewar, G. Jennings, and X.-J. Du Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice Cardiovasc Res, January 14, 2000; 45(2): 330 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-P. Yang, Y.-H. Liu, N.-E. Rhaleb, N. Kurihara, H. E. Kim, and O. A. Carretero Echocardiographic assessment of cardiac function in conscious and anesthetized mice Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1967 - H1974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Scherrer-Crosbie, W. Steudel, R. Ullrich, P. R. Hunziker, N. Liel-Cohen, J. Newell, J. Zaroff, W. M. Zapol, and M. H. Picard Echocardiographic determination of risk area size in a murine model of myocardial ischemia Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H986 - H992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Muthuchamy, K. Pieples, P. Rethinasamy, B. Hoit, I. L. Grupp, G. P. Boivin, B. Wolska, C. Evans, R. J. Solaro, and D. F. Wieczorek Mouse Model of a Familial Hypertrophic Cardiomyopathy Mutation in {alpha}-Tropomyosin Manifests Cardiac Dysfunction Circ. Res., July 9, 1999; 85(1): 47 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Franco, G. D. Thomas, B. Giroir, D. Bryant, M. C. Bullock, M. C. Chwialkowski, R. G. Victor, and R. M. Peshock Magnetic Resonance Imaging and Invasive Evaluation of Development of Heart Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-{alpha} Circulation, January 26, 1999; 99(3): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Scherrer-Crosbie, W. Steudel, P. R. Hunziker, G. P. Foster, L. Garrido, N. Liel-Cohen, W. M. Zapol, and M. H. Picard Determination of Right Ventricular Structure and Function in Normoxic and Hypoxic Mice : A Transesophageal Echocardiographic Study Circulation, September 8, 1998; 98(10): 1015 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. I. Fishman Timing Is Everything in Life : Conditional Transgene Expression in the Cardiovascular System Circ. Res., May 4, 1998; 82(8): 837 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Williams, J. N. Lorenz, S. A. Witt, D. T. Hellard, P. R. Khoury, and T. R. Kimball End-systolic stress-velocity and pressure-dimension relationships by transthoracic echocardiography in mice Am J Physiol Heart Circ Physiol, May 1, 1998; 274(5): H1828 - H1835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bozkurt, S. B. Kribbs, F. J. Clubb Jr, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-{alpha} Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats Circulation, April 14, 1998; 97(14): 1382 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. James, T. E. Hewett, and J. Robbins Cardiac Physiology in Transgenic Mice Circ. Res., March 9, 1998; 82(4): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Franco, S. K. Dubois, R. M. Peshock, and R. V. Shohet Magnetic resonance imaging accurately estimates LV mass in a transgenic mouse model of cardiac hypertrophy Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H679 - H683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. ROHRER and B. K. KOBILKA G Protein-Coupled Receptors: Functional and Mechanistic Insights Through Altered Gene Expression Physiol Rev, January 1, 1998; 78(1): 35 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kameyama, Z. Chen, S. P. Bell, J. Fabian, and M. M. Lewinter Mechanoenergetic studies in isolated mouse hearts Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H366 - H374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kubota, C. F. McTiernan, C. S. Frye, S. E. Slawson, B. H. Lemster, A. P. Koretsky, A. J. Demetris, and A. M. Feldman Dilated Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Tumor Necrosis Factor-{alpha} Circ. Res., October 19, 1997; 81(4): 627 - 635. [Abstract] [Full Text]
|
|
|
|
|
|
G. D. Pennock, D. D. Yun, P. G. Agarwal, P. H. Spooner, and S. Goldman Echocardiographic changes after myocardial infarction in a model of left ventricular diastolic dysfunction Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H2018 - H2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Gottshall, J. J. Hunter, N. Tanaka, N. Dalton, K. D. Becker, J. Ross Jr., and K. R. Chien Ras-dependent pathways induce obstructive hypertrophy in echo-selected transgenic mice PNAS, April 29, 1997; 94(9): 4710 - 4715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tanaka, N. Dalton, L. Mao, H. A. Rockman, K. L. Peterson, K. R. Gottshall, J. J. Hunter, K. R. Chien, and J. Ross Transthoracic Echocardiography in Models of Cardiac Disease in the Mouse Circulation, September 1, 1996; 94(5): 1109 - 1117. [Abstract] [Full Text]
|
|
|
|
|
|
J.G. Edwards, G.E. Lyons, B.K. Micales, A. Malhotra, S. Factor, and L.A. Leinwand Cardiomyopathy in Transgenic myf5 Mice Circ. Res., March 1, 1996; 78(3): 379 - 387. [Abstract] [Full Text]
|
|
|
|
|
|
B. D. Hoit, S. F. Khoury, E. G. Kranias, N. Ball, and R. A. Walsh In Vivo Echocardiographic Detection of Enhanced Left Ventricular Function in Gene-Targeted Mice With Phospholamban Deficiency Circ. Res., September 1, 1995; 77(3): 632 - 637. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Liao, F. Ishikura, S. Beppu, M. Asakura, S. Takashima, H. Asanuma, S. Sanada, J. Kim, H. Ogita, T. Kuzuya, et al. Echocardiographic assessment of LV hypertrophy and function in aortic-banded mice: necropsy validation Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1703 - H1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xiao, S. Mao, G. Baumgarten, J. Serrano, M. C. Jordan, K. P. Roos, M. C. Fishbein, and W. R. MacLellan Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis Circ. Res., December 7, 2001; 89(12): 1122 - 1129. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||