| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine; and 2 Department of Echocardiography, School of Allied Health Science, Osaka University Faculty of Medicine, Osaka 565-0871, Japan
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
We characterized
the time course of the left ventricular (LV) geometric and functional
changes after aortic banding, validated them by necropsy, and
investigated the sensitivity of echocardiographic findings on LV
hypertrophy. C57BL/6 mice were subjected to transverse aortic
constriction (TAC) or sham operation; echocardiographic assessments
were performed before or at 2, 4, 6, and 11 wk after surgery; and some
of the mice were euthanized at the corresponding time points. There was
a progressive increase in diastolic posterior wall thickness and LV
systolic dimension; the percentage of LV fractional shortening (LV%FS)
decreased progressively at 4 wk, whereas these parameters remained
stable in sham-operated mice. Echo LV mass and LV%FS correlated well
with actual whole heart mass and ratio of lung weight to body weight,
respectively (r = 0.765 and 
0.749, respectively;
P < 0.0001). These results suggest that the
development of myocardial hypertrophy and systolic dysfunction is a
time-dependent process. Echocardiographic assessment of myocardial hypertrophy and functional changes correlate well with the actual heart
mass and lung mass. Echocardiography is sensitive enough to assess
myocardial hypertrophy and heart functional changes induced by pressure
overload in mice.
myocardial; heart failure; left ventricular hypertrophy
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
WITH THE ADVENT OF TRANSGENIC TECHNOLOGY, genetically altered mice with remarkable cardiovascular phenotypes have been commonly used in cardiovascular research, and it is an important approach to integrate a genetically engineered mouse with a pressure overload intervention to study the interplay of genes and pathophysiology of cardiac hypertrophy in vivo. However, the murine model of pressure overload by transverse aortic constriction (TAC) is not widely used because it is difficult to prepare the model in such a small animal; microsurgical techniques are thus required (3, 9, 11). Furthermore, it is critically important to develop approaches for accurate and reproducible measurements of cardiac morphology and function in the intact mice with pressure overload.
Transthoracic echocardiography has been reported (5, 8, 14) as a reliable tool for monitoring the changes of cardiac geometry and function in vivo, but serial echocardiographic evaluation of myocardial hypertrophy in mice with TAC has not been extensively performed. Therefore, it is important to confirm the ability of echocardiography to distinguish between differences in severity of cardiac hypertrophy and myocardial function in TAC murine models.
In the present study, we hypothesized that echocardiography is able to monitor the changes of left ventricular (LV) hypertrophy and has the sensitivity to distinguish between differences in severity of disease in TAC mice. To test this hypothesis, we established a murine model of TAC and assessed morphometric and functional characteristics with the use of echocardiography. Furthermore, we validated the results of echocardiographic heart mass by necropsy over a time course and checked the correlation between echocardiographic heart function and the lung weight-to-body weight ratio (LW/BW) to confirm the time point of developing heart failure. The sensitivity of echocardiography was determined by monitoring the changes of hypertrophy over time.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
TAC model. C57BL/6 male mice (9-10 wk, 18-23 g) were anesthetized with a mixture of pentobarbital sodium (50 mg/kg ip) and ketamine (25 mg/kg ip). The animal was placed supine and endotracheal intubation was performed rapidly and safely, as described by Brown et al. (1). The cannula was connected to a volume-cycled rodent ventilator with a tidal volume of 0.5 ml room air and respiratory rate of 110 breaths/min. The chest cavity was entered in the second intercostal space at the left upper sternal border through a small incision. With the help of a light source with two flexible fiberoptic arms, the thymus was then gently deflected out of the field of view to expose the aortic arch. After the transverse aorta was isolated between the carotid arteries, it was constricted by a 7-0 silk suture ligature tied firmly against a 27-gauge needle. The latter was promptly removed to yield a constriction of 0.4 mm in diameter. Sham-operated mice underwent a similar surgical procedure without constriction of the aorta. The chest was closed with a 5-0 silk suture, and mice were allowed to recover from anesthesia with light supply to keep the body temperature at 37°C. The surgical preparation was performed without the use of a microscope and was finished in 30 min. All procedures were performed in accordance with the guiding principles of Osaka University School of Medicine with regard to animal care and the "Position of the American Heart Association on Research Animal Use."
Hemodynamic measurement. Right or left carotid arteries (n = 4), respectively, were isolated and cannulated with polyethylene (PE)-10 tubing under a microscope. The catheters were connected to a pressure transducer to measure system blood pressure. These mice were used to confirm the pressure gradient between the carotid arteries after TAC and were not included in experimental groups for echocardiography assessment because the carotid artery was occluded. Noninvasive blood pressure (BP) and heart rate (HR) were measured before and at 4 and 11 wk after surgery by the tail-cuff plethysmography method in unanesthetized mice prewarmed for 10 min at 37°C in a thermostatically controlled heating cabinet (model BP-98A, Softron).
Two-dimensional guided M-mode echocardiography.
Animals were lightly anesthetized with pentobarbital sodium (30-50
mg/kg ip). Two-dimensional (2-D) guided M-mode echocardiography in the
mouse was performed using an echocardiogram (model 5500, Sonos)
equipped with a 15- to 6L-MHz transducer (Hewlett-Packard). The heart
was imaged in the 2D mode in the parasternal long-axis view with a
depth setting of 2 cm. From this view, an M-mode cursor was positioned
perpendicular to the interventricular septum and posterior wall of the
LV at the level of the papillary muscles. An M-mode image was obtained
at a sweep speed of 100 mm/s. Diastolic and systolic LV wall thickness,
LV end-diastolic dimensions (LVDD), and LV end-systolic chamber
dimensions (LVSD) were measured. All measurements were done from
leading edge to leading edge according to the American Society of
Echocardiography guidelines (8). The percentage of LV
fractional shortening (LV%FS) was calculated as [(LVDD LVSD)/LVDD] × 100. LV mass was calculated according to uncorrected
cube assumptions with some modifications using the equation LV mass
(mg) = 1.055[(LVDD + PWTD + VSTD)3 (LVDD)3] (2, 10), where 1.055 is the gravity
of myocardium, PWTD is diastolic posterior wall thickness, and VSTD is
diastolic ventricular septal thickness.
Experimental protocol. Animals were randomly divided into TAC and sham-operation control groups. After the initial assessment using echocardiography, mice were subjected to TAC or sham operation. At 2, 4, 6, and 11 wk after surgery, echocardiography was performed and 4-13 mice from each group were euthanized to obtain body and organ weights.
Statistical analysis. Values are expressed as means ± SE. Two-tailed Student's t-test was used to compare the differences between groups. The least-squares method was used for linear correlation between selected variables. A variable with skewed distribution was transformed with the use of the logarithm method. Significance was defined as P < 0.05.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Mortality. The mortality rate for TAC was 3.7% (7/188) during operation from anesthesia to chest closure, 10.5% (19/181) during the recovery period from anesthesia, and 19.13% (31/162) after recovery from anesthesia to 2 wk. Most of the postoperative deaths can be attributed to acute or subacute heart failure confirmed by significant increase of LW/BW. Ten mice with early deaths were validated by postmortem. The survival days, heart weight-to-BW ratio (HW/BW), and LW/BW were 6.5 ± 1.4 days, 9.81 ± 0.23 mg/g, and 16.57 ± 1.39 mg/g, respectively. The total mortality was 30.32% for TAC and 0% for sham-operated mice.
Hemodynamics.
The invasive systolic pressure gradient between the right and left
carotid artery after TAC was 50.5 mmHg, which was in agreement with
previous reports (4, 5). The results of tail-cuff BP and
HR, lung weight, and percentage of congestive heart failure before and
at 4 and 11 wk after the surgery are shown in Table 1. Congestive heart failure was defined
as LW/BW > 1.5 times of the mean of LW/BW in sham-operated mice. The
lung weight and LW/BW increased markedly in the TAC mice at 4 wk
compared with the sham-operated group and also showed a tendency of
further increase at 11 wk in the TAC mice, in which no significant
difference was found because of the relatively small sample size.
|
Echocardiographic assessment.
In vivo 2-D-guided M-mode echocardiograms were obtained in banded mice
before and at 2, 4, 6, and 11 wk after TAC (Fig.
1). As reported in Fig.
2, LV diastolic posterior wall thickness
increased progressively from 2 to 11 wk after TAC relative to
age-matched sham-operated mice (all P < 0.01).
Systolic posterior wall thickness increased significantly at 2 wk after
TAC and then presented a plateau. LVSD and LVDD slightly but
significantly decreased in 2 wk in the TAC mice; LVSD increased
noticeably from 4 to 11 wk (P < 0.05 or 0.01) whereas
LVDD increased significantly only at 11 wk after banding compared with
sham-operated mice, which indicates that systolic function was impaired
at the early phase. LV%FS was depressed significantly in a time course
similar to LVSD.
|
|
Correlation of echocardiographic parameters and heart mass at
necropsy.
LV%FS correlated well with LVDD and LVSD (r = 0.778
and 0.918, respectively, both P < 0.0001, n = 111), indicating that LV dilation is associated
with deterioration of systolic function. In the present study, the
depressed ventricular pumping was attributed mainly to the increased
LVSD at several time points because the increase in LVSD was greater
than that in LVDD. As shown in Fig. 3,
the LV mass obtained by echocardiography significantly correlated with
the actual heart mass at necropsy, and LV%FS correlated significantly with the LW/BW. Because the variable LW/BW in this study contained outlying values that may influence the value of correlation
coefficient, we transformed this variable into a logarithm (LW/BW) and
showed a similar result (r = 0.750, P < 0.0001). In addition, the time course of PWTD and HW/BW (Fig. 2),
echo LV mass and actual whole heart mass (Fig.
4) were well coincided; meanwhile, no
differences were found in BW between the TAC mice and sham-operated
controls (Fig. 4A). Actual heart mass correlated
significantly with the PWTD (r = 0.717, P < 0.01, n = 77). The appearance of
hypertrophied heart, congestive lung, and histological findings of
myocardial hypertrophy are shown in Fig.
5.
|
|
|
Sensitivity of echocardiography to monitor the changes of LV
hypertrophy.
To determine the ability of echocardiography to discriminate between
differences in severity of cardiac hypertrophy, we investigated whether
echocardiography could differentiate between mice with a 30% change in
myocardial hypertrophy. As presented in Fig. 4, actual heart mass
increased ~30% between every two adjacent time points (Fig.
4B); the corresponding echo LV mass also significantly increased (Fig. 4C). In addition, we divided the 77 mice
into 4 groups according to their actual heart mass and controlled the increase value not >30% between every two groups; the corresponding echo LV mass also showed a similar increase tendency (Fig.
6).
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
One of the main findings of this study is that the degree of myocardial hypertrophy assessed with echocardiography increased progressively along with the time of banding and was validated by necropsy at different time points. The tendencies of wall thickness and echo LV mass increasing are in accordance with that of the actual whole heart mass. Furthermore, we have checked the sensitivity of echocardiography to discriminate between severity of cardiac hypertrophy and myocardial function in this model and showed that echocardiography could differentiate between mice with a 30% change in LV hypertrophy and logarithm of (LW/BW). The ability to distinguish between differences in severity of cardiac hypertrophy and heart function will be important as attempts are made to manipulate dysfunction in these murine models. There are reports that showed that in ascending aortic constriction (3) and TAC (13) mice actual heart mass increased over time, but they did not analyze the relation between echocardiographic measurements and actual heart mass. A recent study (4) of nine ascending aortic-banded mice reported that echo LV mass peaked at 3 wk and presented a plateau thereafter until 8 wk but had no validation by postmortem examination at different time points. Hill et al. (7) validated echocardiographic calculated LV mass by necropsy in six mice of different ages (not aortic-banded mice), but they did not check the correlation between the findings by echocardiography and the postmortem results in TAC model at different time points. Therefore, our study may be the first to validate the echocardiographic measurements by necropsy on different time points with relatively long time course in TAC murine model.
In the present study, significant depressed systolic function developed
as early as 4 wk after the banding and gradually deteriorated over
time, which was validated by pulmonary congestion. Gardin et al.
(6) also reported that LV%FS inversely correlated with the ratio of lung mass to body mass in 15 mice (r = 0.79), which is similar to our results. We also showed that heart
function declined markedly from 4 wk, which was validated by pulmonary congestion. Meanwhile, LV%FS also decreased significantly from the 4 wk after TAC, and a similar tendency presented in LVSD, indicating that
the impaired systolic function should be attributed largely to the
increase in systolic dimension because the diastolic dimension did not
increase at least before 7 wk after TAC. The systolic wall thickness
did not increase progressively after 2 wk, also suggesting impaired
systolic function. These findings imply that the impairment of systolic
heart function can be developed before the occurrence of eccentric hypertrophy.
The normal values of LV dimensions and wall thickness in mice have been reported differently in small sampling size (5, 8, 13-16). We obtained the normal values using a relatively large sample size (n = 92), which is consistent with other studies (5, 14, 15).
In conclusion, the present study provides strong evidence that the development of myocardial hypertrophy and systolic dysfunction in the murine model of TAC is a time-dependent process. Echocardiography is a reliable and sensitive means to study the process of LV remolding and functional changes induced by pressure overload.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: M. Kitakaze, Dept. of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan (E-mail: kitakaze{at}zfb.so-net.ne.jp).
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.
First published December 13, 2001;10.1152/ajpheart.00238.2001
Received 24 March 2001; accepted in final form 11 December 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Brown, R,
Walters DM,
Greenberg RS,
and
Mitzner W.
A method of endotracheal incubation and pulmonary functional assessment for repeated studied in mice.
J Appl Physiol
87:
2362-2365,
1999.
2.
De Simone, G,
Wallerson DC,
Volpe M,
and
Devereux RB.
Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats: necropsy validation.
Am J Hypertens
3:
688-696,
1990.
3.
Ding, B,
Price RL,
Goldsmith EC,
Borg TK,
Yan X,
Douglas PS,
Weinberg EO,
Bartunek J,
Thielen T,
Didenko VV,
and
Lorell BH.
Left ventricular hypertrophy in ascending aortic stenosis mice.
Circulation
101:
2854-2862,
2000.
4.
Fard, A,
Wang CY,
Takuma S,
Skopicki HA,
Pinsky DJ,
Di Tullio MR,
and
Homma S.
Noninvasive assessment and necropsy validation of changes in left ventricular mass in ascending aortic banded mice.
J Am Soc Echocardiogr
13:
582-587,
2000.
5.
Gao, XM,
Dart AM,
Dewar E,
Jennings G,
and
Du XJ.
Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice.
Cardiovasc Res
45:
330-338,
2000.
6.
Gardin, JM,
Siri FM,
Kitsis RN,
Edwards JG,
and
Leinwand LA.
Echocardiographic assessment of left ventricular mass and systolic function in mice.
Circ Res
76:
907-914,
1995.
7.
Hill, JA,
Karimi M,
Kutschke W,
Davission RL,
Zimmerman K,
Wang Z,
Kerber RE,
and
Weiss RM.
Cardiac hypertrophy is not a required compensatory response to short-term pressure overload.
Circulation
101:
2863-2869,
2000.
8.
Manning, WJ,
Wei JY,
Katz SE,
Litwin SE,
and
Douglas PS.
In vivo assessment of LV mass in mice using high-frequency cardiac ultrasound: necropsy validation.
Am J Physiol Heart Circ Physiol
266:
H1672-H1675,
1994.
9.
Meguro, T,
Hong C,
Asai K,
Takagi G,
McKinsey TA,
Olson EN,
and
Vatner SF.
Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure.
Circ Res
84:
735-740,
1999.
10.
Pollick, C,
Hale SL,
and
Kloner RA.
Echocardiographic and cardiac Doppler assessment of mice.
J Am Soc Echocardiogr
8:
602-610,
1995.
11.
Rockman, HA,
Ross RS,
Harris AN,
Knowlton KU,
Steinhelper ME,
Field LJ,
Ross JRJ,
and
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 USA
88:
8277-8281,
1991.
12.
Sahn, DJ,
DeMaria A,
Kisslo J,
and
Weyman A.
Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.
Circulation
58:
1072-1083,
1978.
13.
Sakata, Y,
Hoit BD,
Liggett SB,
Walsh RA,
and
Dorn GW.
Decompensation of pressure-overload hypertrophy in G
q-overexpressing mice.
Circulation
97:
1488-1495,
1998.
14.
Tanaka, N,
Dalton N,
Mao L,
Rockman HA,
Peterson KL,
Gottshall KR,
Hunter JJ,
Chien KR,
and
Ross J.
Transthoracic echocardiography in models of cardiac disease in the mouse.
Circulation
94:
1109-1117,
1996.
15.
Yang, XP,
Liu YH,
Rhaleb NE,
Kurihara N,
Kim HE,
and
Carretero OA.
Echocardiographic assessment of cardiac function in conscious and anesthetized mice.
Am J Physiol Heart Circ Physiol
277:
H1967-H1974,
1999.
16.
Youn, HJ,
Rokosh G,
Lester SJ,
Simpson P,
Schiller NB,
and
Foster E.
Two-dimensional echocardiography with a 15-MHz transducer is a promising alternative for in vivo measurement of left ventricular mass in mice.
J Am Soc Echocardiogr
12:
70-75,
1999.
This article has been cited by other articles:
|
|
 |
|
  T. Urashima, M. Zhao, R. Wagner, G. Fajardo, S. Farahani, T. Quertermous, and D. Bernstein Molecular and physiological characterization of RV remodeling in a murine model of pulmonary stenosis Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1351 - H1368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Hruz, Q. Yan, H. Struthers, and P. Y. Jay HIV protease inhibitors that block GLUT4 precipitate acute, decompensated heart failure in a mouse model of dilated cardiomyopathy FASEB J, July 1, 2008; 22(7): 2161 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Kompa, F. See, D. A. Lewis, A. Adrahtas, D. M. Cantwell, B. H. Wang, and H. Krum Long-Term but Not Short-Term p38 Mitogen-Activated Protein Kinase Inhibition Improves Cardiac Function and Reduces Cardiac Remodeling Post-Myocardial Infarction J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 741 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mito, R. Ozono, T. Oshima, Y. Yano, Y. Watari, Y. Yamamoto, A. Brydun, K. Igarashi, and M. Yoshizumi Myocardial Protection Against Pressure Overload in Mice Lacking Bach1, a Transcriptional Repressor of Heme Oxygenase-1 Hypertension, June 1, 2008; 51(6): 1570 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Chess, B. Lei, B. D. Hoit, A. M. Azimzadeh, and W. C. Stanley Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1853 - H1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Barrick, M. Rojas, R. Schoonhoven, S. S. Smyth, and D. W. Threadgill Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal- and background-dependent development of concentric left ventricular hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2119 - H2130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liao, S. Takashima, H. Zhao, Y. Asano, Y. Shintani, T. Minamino, J. Kim, M. Fujita, M. Hori, and M. Kitakaze Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice Cardiovasc Res, April 1, 2006; 70(1): 107 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamamoto, M. Ohishi, T. Katsuya, N. Ito, M. Ikushima, M. Kaibe, Y. Tatara, A. Shiota, S. Sugano, S. Takeda, et al. Deletion of Angiotensin-Converting Enzyme 2 Accelerates Pressure Overload-Induced Cardiac Dysfunction by Increasing Local Angiotensin II Hypertension, April 1, 2006; 47(4): 718 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsusaka, T. Ide, S. Matsushima, M. Ikeuchi, T. Kubota, K. Sunagawa, S. Kinugawa, and H. Tsutsui Targeted Deletion of Matrix Metalloproteinase 2 Ameliorates Myocardial Remodeling in Mice With Chronic Pressure Overload Hypertension, April 1, 2006; 47(4): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liao, S. Takashima, N. Maeda, N. Ouchi, K. Komamura, I. Shimomura, M. Hori, Y. Matsuzawa, T. Funahashi, and M. Kitakaze Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism Cardiovasc Res, September 1, 2005; 67(4): 705 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Gao, H. Kiriazis, X.-L. Moore, X.-H. Feng, K. Sheppard, A. Dart, and X.-J. Du Regression of pressure overload-induced left ventricular hypertrophy in mice Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2702 - H2707. [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]
|
|
|
|
|
|
Y. Liao, M. Asakura, S. Takashima, A. Ogai, Y. Asano, H. Asanuma, T. Minamino, H. Tomoike, M. Hori, and M. Kitakaze Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice Cardiovasc Res, March 1, 2005; 65(4): 879 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Hartley, A. K. Reddy, S. Madala, M. L. Entman, L. H. Michael, and G. E. Taffet Noninvasive ultrasonic measurement of arterial wall motion in mice Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1426 - H1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Zhou, F. S. Foster, B. J. Nieman, L. Davidson, X. J. Chen, and R. M. Henkelman Comprehensive transthoracic cardiac imaging in mice using ultrasound biomicroscopy with anatomical confirmation by magnetic resonance imaging Physiol Genomics, July 8, 2004; 18(2): 232 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Parker and M. I. Townsley Evaluation of lung injury in rats and mice Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L231 - L246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ogita, K. Node, Y. Liao, F. Ishikura, S. Beppu, H. Asanuma, S. Sanada, S. Takashima, T. Minamino, M. Hori, et al. Raloxifene Prevents Cardiac Hypertrophy and Dysfunction in Pressure-Overloaded Mice Hypertension, February 1, 2004; 43(2): 237 - 242. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liao, S. Takashima, Y. Asano, M. Asakura, A. Ogai, Y. Shintani, T. Minamino, H. Asanuma, S. Sanada, J. Kim, et al. Activation of Adenosine A1 Receptor Attenuates Cardiac Hypertrophy and Prevents Heart Failure in Murine Left Ventricular Pressure-Overload Model Circ. Res., October 17, 2003; 93(8): 759 - 766. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
