© 1995 American Heart Association, Inc.
Articles |
In Vivo Echocardiographic Detection of Enhanced Left Ventricular Function in Gene-Targeted Mice With Phospholamban Deficiency
From the Division of Cardiology (B.D.H., S.F.K., N.B., R.A.W.) and the Department of Pharmacology and Cell Biophysics (E.G.K.), University of Cincinnati (Ohio).
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Abstract We evaluated the ability of M-mode and Doppler echocardiography to assess left ventricular (LV) function reliably and repeatedly in mice and tested whether these techniques could detect physiological alterations in phospholamban (PLB)–deficient mice. Anesthetized wild-type mice (n=7) and mice deficient in PLB (n=8) were studied with two-dimensional guided M-mode and Doppler echocardiography using a 9-MHz imaging and 5- to 7.5-MHz Doppler transducer. Data were acquired in the baseline state and after intraperitoneal isoproterenol administration (2.0 µg/g IP). Interobserver and intraobserver variability and reproducibility were excellent. PLB-deficient mice were associated with significant (P<.05) increases in several physiological parameters (mean±SD) compared with wild-type control mice: normalized mean velocity of circumferential shortening (7.7±2.1 versus 5.5±1.0 circ/sec), peak aortic velocity (105±13 versus 75±9.2 cm/s), mean aortic acceleration (57±16 versus 31±4 m/s2), and peak early-diastolic transmitral velocity (80.0±7.2 versus 66.9±7.7 cm/s). LV dimensions, shortening fractions, heart rates, late diastolic transmitral (A) velocities, and early to late (E/A) diastolic velocity ratios were similar in both groups. Isoproterenol administration resulted in significant increases in Doppler indices of ventricular function in control but not PLB-deficient mice. These findings indicate that assessment of LV function can be performed noninvasively in mice under varying physiological conditions and that PLB regulates basal LV function in vivo.
Key Words: echocardiography • gene targeting • phospholamban • sarcoplasmic reticulum • left ventricular function
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Manipulation of the mammalian genome with transgenic techniques is emerging as a powerful method for definitively identifying the molecular mechanisms underlying cardiac development and function. Although a variety of animal species have been used in transgenic experiments, the mouse has been studied most extensively. The predominant use of mice in transgenic investigations reflects their relatively low cost, their well-characterized genome, the availability of numerous in-bred lines, and the ability to perform rapid linkage analysis.1 Despite these considerable advantages, the functional analysis of the transgenic phenotype in the intact animal has been limited by the small size of the mouse.
Recently, investigators have attempted to image the murine heart in vivo. Right ventricular function was assessed by quantitative angiography in a murine model of right ventricular pressure-overload hypertrophy (Rockman et al2 ). However, ventriculography is invasive, requires microsurgical techniques and contrast injections, and has limited temporal resolution. Moreover, in the study of Rockman et al, 40% of densitometric studies were unsuitable for analysis. Although radiolabeled microsphere and indicator dilution techniques have been used for cardiac output and stroke volume determinations in both conscious and anesthetized mice,3 these methods are technically demanding and do not directly assess ventricular function.
M-mode echocardiography is an attractive alternative because of its ability to noninvasively and repeatedly assess ventricular dimensions and shortening with both high temporal and (with appropriate transducer frequency) spatial resolutions. M-mode echocardiography has been shown by Manning et al4 to provide accurate estimates of murine LV mass; however, in that study, ventricular function was not assessed, and the ability to quantify physiological changes by using in vivo Doppler echocardiographic techniques was not determined. More recently, Gardin et al5 presented data to support the feasibility of M-mode echocardiographic evaluation of LV mass and systolic function in mice.
LV function can also be quantified by Doppler echocardiographic interrogation of transvalvular flows. Aortic Doppler waveform analysis can be used to estimate LV stroke volume and assess LV systolic performance.6 7 Peak aortic velocity and mean acceleration were highly correlated with maximal dP/dt, peak flow, and maximum flow rate in a highly instrumented canine model; moreover, correlations were not appreciably influenced by adjustments for heart rate and preload.6 Transmitral Doppler waveform analysis provides insight into the temporal distribution of LV filling; diastolic filling patterns (eg, E/A ratios) characteristic of impaired LV relaxation and reduced ventricular compliance are described.8
Accordingly, the overall goal of the present investigation was to develop reliable methods to noninvasively assess LV function by using M-mode and pulsed-wave Doppler echocardiography in the mouse. An important related objective was to evaluate the ability of these techniques to characterize a well-defined genetic model with altered cardiac biochemical and physiological parameters. Recent studies using the isolated working heart indicate that the phosphoprotein PLB plays critical roles in SR function, basal myocardial contractility, and the contractile responses to ß-adrenergic agonists ex vivo.9 Therefore, we performed echocardiographic studies before and after isoproterenol administration in transgenic mice with PLB deficiency and in wild-type control mice to test the hypothesis that PLB regulates basal LV contractile function and modulates the sensitivity to ß-adrenergic agonists in vivo.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Mice of either sex (Charles River Laboratories, Wilmington, Mass), 10 to 12 weeks of age and weighing 23.6 to 40 g (29.1±5.2 g), were used in these studies. Mice were anesthetized with 0.1 mL/g of a mixture of 65% ketamine, 22% acepromazine, and 13% xylazine (at a concentration of 10 mg/mL each and prepared as a 1:10 dilution) and were allowed to breathe spontaneously. Oxygen was delivered at 2 L/min via a nose cone. The chest was shaved, and ECG leads were attached to each limb with needle electrodes (Grass Instruments). The extremities were secured to the examining surface with paper tape. A warming pad (Deltaphase isothermal pad, Braintree Scientific) was used to maintain normothermia.
Studies were performed in mice with PLB deficiency that were obtained by gene-targeting methodology (PLB-KO mice, n=8) and in age-matched CF-1 mice (control mice, n=7). The control group included two wild-type littermates and five CF-1 mice. PLB-targeted mice were generated from CF-1 and C57Bl/6 strains by using methods previously described.9
Cardiac ultrasound studies were performed with an Interspec Apogee X-200 ultrasonograph (Interspec-ATL). A dynamically focused 9-MHz annular array transducer (axial resolution, 0.2 mm) was placed on a layer of acoustic coupling gel that was applied to the left hemithorax; care was taken to maintain adequate contact while avoiding excessive pressure on the chest. Mice were imaged in a shallow left lateral decubitus position; short- and long-axis views of the LV were obtained by slight angulation and rotation of the transducer. Two-dimensional targeted M-mode studies were generally taken from the short axis (at the level of the largest LV diameter), but occasionally, endocardial echoes were best defined from the long-axis view.
Aortic outflow and diastolic transmitral LV inflow velocities were interrogated from angulated parasternal long-axis views by using a pulsed-wave Doppler (5- to 7.5-MHz) transducer with a sample volume length of 3.5 to 7.5 mm. The Doppler instrument has a sampling frequency of 4 to 35.7 kHz and a minimum computation time of 1 millisecond. Echoes from the mitral valve annulus and aortic root were readily defined, and color flow-mapping Doppler assisted the sample volume placement. Attempts were made to align the ultrasound beam as parallel as possible to flow and to record the highest velocities.
Studies were recorded on 1/2-in S-VHS videotape (Sony 9500 VCR, Sony Corp). Freeze frames were printed (either on-line or off-line from digital archival storage) on a Sony color video printer (UP-5200, Sony Corp). The limb-lead ECG was patched into the ultrasonograph for timing purposes.
Experimental Protocol
Two-dimensionally targeted M-mode and color flow mapping–guided
pulsed-wave Doppler studies were performed at baseline and after
the administration of 2.0 µg/g IP isoproterenol. Heart rate responses
to isoproterenol were maximal within 1 to 2 minutes after injection.
Imaging sequences were generally completed within 10 to 15 minutes. The
experimental protocol was approved by the Institutional Animal Care and
Use Committee at the University of Cincinnati.
Data Analysis
M-mode measurements of LV EDD and ESD were made from original
tracings (Fig 1
) (SIGMA
PLOT, Jandel Scientific) by using the leading-edge
convention of the American Society of
Echocardiography and by using the steepest
continuous endocardial echoes. End diastole was taken at
the onset of the QRS complex, and end systole was taken at the peak of
posterior wall motion. Three beats were averaged for each
measurement.
|
LV FS was calculated as follows: (EDD-ESD)/EDD.
The normalized mean Vcf was calculated as follows: FS/ET, where ET was taken from heart rate–matched aortic Doppler spectra.
Spectral Doppler waveforms were analyzed for peak early-
and late-diastolic transmitral velocities, the peak and
integral velocities of aortic flow, and aortic acceleration and ETs
(Fig 2) from videotape playback using a commercially
available image analysis system (Freeland Medical). Mean
acceleration was calculated as follows: peak aortic
velocity/acceleration time. Three to five beats were averaged for each
measurement.
|
Interpretative Variability
A total of 108 beats were selected at random from nine animals
and were analyzed for LV dimensions and wall thickness (n=36)
and transmitral (n=36) and aortic Doppler (n=36) velocities by two
observers (B.D.H. and S.F.K.). A single observer (S.F.K.) repeated
M-mode echocardiographic measurements from 108 beats
several days later. To determine reproducibility, studies were repeated
on separate days in five mice and analyzed in a blinded
fashion.
Interobserver and intraobserver differences were calculated as the difference between two observations divided by the mean of the observations and were expressed as percentages. Interobserver and intraobserver variability was also quantified by the limits of agreement, defined as the mean difference between observations (±2 SD).10 Reproducibility was calculated as the difference between two determinations divided by the mean of the two determinations and was expressed as a percentage. In view of the small number of animals studied, variability was also quantified as the mean difference of two determinations and the range of those differences.
Statistical Analysis
All data are presented as mean±SD. M-mode
echocardiographic and Doppler
parameters were compared at baseline in control and
PLB-deficient mice with unpaired t tests. Paired
t tests were used to compare baseline and
isoproterenol-stimulated states in each group of animals. A value of
P<.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Interpretative Variability and Reproducibility
Technically adequate M-mode and Doppler studies were obtained in all mice. Interobserver and intraobserver variability for M-mode dimension and wall thickness and Doppler measurements is summarized in Table 1
. The interobserver and intraobserver
variabilities for LV cavity dimensions and FS and
Doppler-determined variables were excellent; LV wall thickness
determinations exhibited greater variability.
|
Reproducibility data for M-mode and Doppler studies are summarized
in Table 2. LV dimension and FS measurements made in the
same animals on separate days were highly reproducible; wall thickness
measurements were less reproducible. Doppler determinations
exhibited considerably less reproducibility; these indices were
influenced greatly by the disparate heart rates on the two separate
days.
|
Baseline Echocardiographic
Measurements
M-mode and Doppler echocardiographic
measurements in PLB-deficient and wild-type control mice are compared
in Table 3. EDD, ESD, and the FS were similar in both
groups. In contrast, Vcf was significantly greater in PLB-deficient
than wild-type control mice.
|
Compared with control mice, PLB-deficient mice had higher peak aortic velocity, shorter acceleration time, and consequently, greater mean aortic acceleration. The aortic velocity time integral, however, was similar in both groups.
Peak early-diastolic transmitral velocity was greater, and there was a trend (P=.09) toward greater late-diastolic velocity in PLB-deficient mice than in control mice; the E/A ratio did not differ in the two groups.
Heart rates were slightly but not significantly greater in PLB-deficient mice than in control mice. To determine whether differences in M-mode and Doppler-derived indices resulted partly from heart rate effects, data were analyzed after excluding two (PLB-deficient) outliers with rapid basal heart rates (604 and 504 bpm). Despite nearly identical heart rates, significant differences in peak aortic and early-diastolic velocities, aortic acceleration time, and mean acceleration persisted; differences in Vcf became of borderline significance (P=.07).
Effects of ß-Adrenergic Stimulation
The effects of the intraperitoneal
administration of the ß-adrenergic agonist isoproterenol on M-mode
and Doppler measurements in control and PLB-deficient mice are
illustrated in Fig 3 and are summarized in Table 3
. In
control mice, isoproterenol caused significant increases in heart rate,
LV FS, Vcf, and Doppler-derived aortic and early- and
late-diastolic velocities and significant decreases in
aortic acceleration time and the E/A ratio. In PLB-deficient
mice, isoproterenol caused significant increases in heart rate, LV FS,
and Vcf; however, peak aortic and early- and late-diastolic
transmitral velocities and aortic acceleration did not change
significantly.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The major findings of the present study are as follows: (1) M-mode and Doppler echocardiography provide precise repeatable measurements of in vivo LV performance and transvalvular velocities in the mouse. (2) These in vivo noninvasive techniques can detect changes in LV function in mice with altered PLB expression.
The development of gene-targeting technology in mice has provided the opportunity to determine, unambiguously, the functions of a specific gene product in the intact mammal.1 11 However, efforts to quantify basal myocardial function and the changes in function produced by an experimental intervention in the transgenic mouse have been limited. Recently, pressure-derived indices in the murine isolated working heart and myocyte preparations were used to quantify myocardial performance.11 12 13 Despite the ability to determine physiological end points with high resolution and under controlled loading conditions, approaches at the isolated heart and myocyte levels have certain limitations. First, in vitro techniques require killing the animal, precluding serial studies of ventricular function. Second, the isolated heart and myocyte preparations are devoid of autonomic reflexes and ventriculovascular interaction; thus, significant differences in ventricular performance may exist in vivo compared with isolated preparations.
By contrast, echocardiography is a relatively
simple technique that allows repetitive noninvasive assessment of LV
function. The small size of the murine heart and the rapid heart rates
encountered (
600 bpm in the unanesthetized mouse; Dr I.L.
Grupp, oral personal communication, 1994) have, in the past, limited
echocardiographic assessment of the murine heart.
However, in the present study, the use of a dynamically focused
annular array transducer operating at a higher (9-MHz) frequency
resulted in highly reliable and reproducible image quality. The annular
array focuses the ultrasound beam in axial, lateral, and elevational
planes, thereby increasing the signal-to-noise ratio.14
Because of its high sampling rate (1000/s), M-mode
echocardiography provides excellent temporal
resolution; unfortunately, this occurs at the expense of spatial
resolution (ie, a unidimensional "ice pick" view of the heart is
produced). Therefore, this technique is well suited only for ventricles
with uniform geometry and wall motion. Although two-dimensional
echocardiography potentially overcomes problems
owing to regional differences, the relatively slow frame rates (30 Hz)
and the limited acoustic windows and imaging planes available in the
murine model remain significant limitations. Fortunately, Doppler
interrogation of transvalvular flows permits assessment of
global LV systolic and diastolic function without regard
for ventricular geometry.
PLB is an inhibitor of the Ca2+-ATPase in cardiac SR.15 Ablation of PLB leads to enhanced rates of SR Ca2+ uptake (resulting in increased rates of myocardial relaxation) and consequently larger amounts of SR Ca2+ available for release (resulting in increased rates of contraction).16 In isolated work-performing hearts from PLB-deficient mice, the times to peak pressure and half-relaxation were significantly shorter, and peak positive and negative dP/dt values were significantly greater in PLB-deficient mice than in their wild-type littermates.9 In the present study, Vcf, mean aortic acceleration, and peak aortic velocity were significantly greater in PLB-deficient mice than in control mice. However, LV FS was similar in PLB-deficient mice and their wild-type controls. The discrepancy between our in vivo FS results and measurements in isolated work-performing hearts may be explained by different experimental preparations and methods used to characterize ventricular function and/or in vivo compensatory mechanisms that serve to maintain basal LV performance. In the isolated work-performing heart, isovolumic indices were measured, and comparisons between groups were made with similar heart rates, venous return, afterload, and coronary perfusion. In contrast, LV performance in the intact heart is modified by interaction with cardiovascular reflexes, uncontrolled loading conditions, and coupling to the arterial circulation. Moreover, our findings are influenced by the cardiodepressant effects of anesthesia. The ejection phase indices used in the present study are load and heart rate dependent; although preload (as determined from EDD) was similar between the two groups, heart rates tended to be greater in PLB-deficient than control mice. In this regard, it is important to note that when data were analyzed after excluding two PLB-deficient mice with excessively rapid basal heart rates, the differences (except for heart rate and Vcf) between the PLB-deficient and control groups persisted. The trend toward higher heart rates in PLB-deficient mice than in wild-type mice is unlikely to be due to an influence of PLB on the sinus node, since their heart rates are similar in the unanesthetized state9 ; although unlikely, a differential effect of PLB on anesthetic-induced cardiac slowing cannot be excluded.
Noninvasive indices of LV diastolic function derived from transmitral waveform analysis are difficult to interpret because they are influenced by many physiological and pathophysiological factors, such as loading conditions, heart rate, age, and atrial function.17 The peak early-diastolic transmitral velocity, which reflects the early-diastolic transmitral gradient, was significantly greater in PLB-deficient mice than in control mice. However, it is not known whether the difference in early-diastolic velocity that we observed is due to the greater left atrial pressure and/or enhanced LV isovolumic relaxation in PLB-deficient mice than in control mice. Similarly, whether the higher atrial systolic velocities in PLB-deficient mice compared with control mice are the result of increased heart rate or are due to altered left atrial contractility and/or load cannot be determined from our study. As our reproducibility data indicate, Doppler indices of diastolic function should be used cautiously.
Several studies have indicated that phosphorylation of PLB and relief of its inhibitory effects on the SR Ca2+-ATPase is mediated by ß-adrenergic activation of adenyl cyclase.16 18 Therefore, we determined the effects of ß-adrenergic stimulation on LV function in intact mice. In PLB-deficient mice, although isoproterenol increased LV FS, Vcf, and heart rate, there were no significant effects on peak aortic and diastolic transmitral velocities and mean aortic acceleration. In contrast, isoproterenol caused significant increases in all M-mode and Doppler-derived functional indices in control mice. Thus, these data confirm and extend findings in the isolated work-performing heart9 and support the hypothesis that PLB modulates myocardial contractile sensitivity to ß-adrenergic stimulation. Moreover, these data suggest that velocity-dependent indices (eg, mean acceleration) are more likely to be affected by an alteration in SR Ca2+-ATPase activity than are force-dependent indices (eg, FS), which are influenced by the number and strength of actin-myosin cross-bridges. It should be recognized that loading conditions were uncontrolled in the present study; therefore, we cannot exclude the possibility that these indices were influenced differentially by isoproterenol-induced alterations in loading conditions.
In conclusion, noninvasive in vivo assessment of LV performance with M-mode and Doppler echocardiography in the mouse is feasible and reproducible and can assess physiological changes elicited by acute interventions and altered cardiovascular phenotypes. These approaches should prove useful in determining the interplay between altered cardiovascular gene expression and compensatory physiological cardiovascular regulation in the transgenic mouse. Moreover, this in vivo approach permits the assessment of age-related cardiovascular changes serially over time and the effects of pharmacological interventions and/or therapeutic agents in the intact animal. These techniques should complement and extend information derived from isolated myocyte and isolated heart studies.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This study was supported by National Institutes of Health grants HL-33579, HL-26057, and HL-22619 and SCOR grant P50-HL-52318-01. We gratefully acknowledge the expert secretarial assistance of Norma Burns and the technical assistance of Rick Willis and Zouping Zhou. We are grateful to Dr Wusheng Luo for providing the PLB-deficient mice.
|
Footnotes |
|---|
Reprint requests to Brian D. Hoit, MD, Division of Cardiology, University of Cincinnati, PO Box 670542, Cincinnati, OH 45267-0542.
Received February 2, 1995; accepted May 22, 1995.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Field LJ. Transgenic mice in cardiovascular research. Annu Rev Physiol. 1993;55:97-114. [Medline] [Order article via Infotrieve]
2.
Rockman HA, Ono S, Ross RS, Jones LR, Karimi M,
Bhargava V, Ross J, Chien KR. Molecular and
physiological alterations in murine
ventricular dysfunction. Proc Natl Acad Sci
U S A. 1994;91:2694-2698.
3.
Barbee RW, Berry BD, Re RN, Murgo JP.
Microsphere and dilution techniques for the
determination of blood flows and volumes in conscious mice.
Am J Physiol. 1992;263:R728-R733.
4.
Manning WJ, Wei JY, Katz SE, Litwin SE, Douglas PS.
In vivo assessment of LV mass in mice using high-frequency
cardiac ultrasound: necropsy validation. Am J
Physiol. 1994;266:H1672-H1675.
5.
Gardin JM, Siri FM, Kitsis RN, Edwards JG, Leinwand
LA. Echocardiographic assessment of left
ventricular mass and systolic function in mice.
Circ Res. 1995;76:907-914.
6.
Wallmeyer K, Wann S, Sagar KB, Kalbfleisch J,
Klopfenstein HS. The influence of preload and heart rate on
Doppler echocardiographic indexes of left
ventricular performance: comparison with invasive
indexes in an experimental preparation.
Circulation. 1986;74:181-186.
7.
Sabbah HN, Khaja BS, Brymer JF, McFarland TM, Albert
DE, Snyder JE, Goldstein S, Stein PD. Noninvasive evaluation of
left ventricular performance based on peak aortic
blood acceleration measured with a continuous-wave Doppler velocity
meter. Circulation. 1986;74:323-329.
8. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988;12:426-440. [Abstract]
9.
Luo W, Grupp IL, Harrer J, Ponniah S, Grupp G, Duffy
JJ, Doetschman T, Kranias EG. Targeted ablation of the
phospholamban gene is associated with markedly enhanced myocardial
contractility and loss of ß-agonist
stimulation. Circ Res. 1994;75:401-409.
10. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307-310. [Medline] [Order article via Infotrieve]
11.
Ng WA, Grupp IL, Subramaniam A, Robbins J.
Cardiac myosin heavy chain mRNA expression and myocardial
function in the mouse heart. Circ Res. 1991;68:1742-1750.
12.
Grupp IL, Subramaniam 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:H1401-H1410.
13.
Dorn GW II, Robbins J, Ball N, Walsh RA. Myosin
heavy chain regulation and myocyte contractile depression after LV
hypertrophy in aortic-banded mice. Am J
Physiol. 1994;267:H400-H405.
14. Faletra F, Cipriani M, Corno R, Cali G, Mantero A, Cantoni S, Formentini A, Battista Danzi G, Pezzano A. Transthoracic high-frequency echocardiographic detection of atherosclerotic lesions in the descending portion of the left coronary artery. J Am Soc Echocardiogr. 1993;6:290-298.[Medline] [Order article via Infotrieve]
15.
Kim HW, Steenaart NAE, Ferguson DG, Kranias EG.
Functional reconstruction of the cardiac sarcoplasmic reticulum
Ca2+ ATPase with phospholamban in phospholipid
vesicles. J Biol Chem. 1990;265:1702-1709.
16. Kranias EG, Solaro RJ. Phosphorylation of troponin I and phospholamban during catecholamine stimulation of rabbit heart. Nature. 1982;298:182-184. [Medline] [Order article via Infotrieve]
17. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography, I: physiologic and pathophysiologic features. Mayo Clin Proc. 1989;64:71-81. [Medline] [Order article via Infotrieve]
18. Garvey JL, Kranias EG, Solaro RJ. Phosphorylation of C-protein, troponin I and phospholamban in isolated rabbit hearts. Biochem J. 1988;249:709-714.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  J. Stypmann, M. A Engelen, C. Troatz, M. Rothenburger, L. Eckardt, and K. Tiemann Echocardiographic assessment of global left ventricular function in mice Lab Anim, April 1, 2009; 43(2): 127 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. MacDonnell, G. Garcia-Rivas, J. A. Scherman, H. Kubo, X. Chen, H. Valdivia, and S. R. Houser Adrenergic Regulation of Cardiac Contractility Does Not Involve Phosphorylation of the Cardiac Ryanodine Receptor at Serine 2808 Circ. Res., April 25, 2008; 102(8): e65 - e72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yasuda, P. Coutu, S. Sadayappan, J. Robbins, and J. M. Metzger Cardiac Transgenic and Gene Transfer Strategies Converge to Support an Important Role for Troponin I in Regulating Relaxation in Cardiac Myocytes Circ. Res., August 17, 2007; 101(4): 377 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhao, Q. Yuan, J. Qian, J. R. Waggoner, A. Pathak, G. Chu, B. Mitton, X. Sun, J. Jin, J. C. Braz, et al. The Presence of Lys27 Instead of Asn27 in Human Phospholamban Promotes Sarcoplasmic Reticulum Ca2+-ATPase Superinhibition and Cardiac Remodeling Circulation, February 21, 2006; 113(7): 995 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mattiazzi, C. Mundina-Weilenmann, C. Guoxiang, L. Vittone, and E. Kranias Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions Cardiovasc Res, December 1, 2005; 68(3): 366 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Zhou, Y. Zhu, J. Bishop, L. Davidson, R. M. Henkelman, B. G. Bruneau, and F. S. Foster Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H992 - H1001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsuki, K. Isoda, R. Horai, A. Nakajima, Y. Aizawa, K. Suzuki, F. Ohsuzu, and Y. Iwakura Involvement of Tumor Necrosis Factor-{alpha} in the Development of T Cell-Dependent Aortitis in Interleukin-1 Receptor Antagonist-Deficient Mice Circulation, August 30, 2005; 112(9): 1323 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Sebag, M. D. Handschumacher, F. Ichinose, J. G. Morgan, R. Hataishi, A. C. T. Rodrigues, J. L. Guerrero, W. Steudel, M. J. Raher, E. F. Halpern, et al. Quantitative Assessment of Regional Myocardial Function in Mice by Tissue Doppler Imaging: Comparison With Hemodynamics and Sonomicrometry Circulation, May 24, 2005; 111(20): 2611 - 2616. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
A. M Janczewski, M. Zahid, B. H Lemster, C. S Frye, G. Gibson, Y. Higuchi, E. G Kranias, A. M Feldman, and C. F McTiernan Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model Cardiovasc Res, June 1, 2004; 62(3): 468 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R Pena and B. M Wolska Troponin I phosphorylation plays an important role in the relaxant effect of {beta}-adrenergic stimulation in mouse hearts Cardiovasc Res, March 1, 2004; 61(4): 756 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Metzger and M. V. Westfall Covalent and Noncovalent Modification of Thin Filament Action: The Essential Role of Troponin in Cardiac Muscle Regulation Circ. Res., February 6, 2004; 94(2): 146 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Q. Zhou, F. S. Foster, R. Parkes, and S. L. Adamson Developmental changes in left and right ventricular diastolic filling patterns in mice Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1563 - H1575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Said, L. Vittone, C. Mundina-Weilenmann, P. Ferrero, E. G. Kranias, and A. Mattiazzi Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1198 - H1205. [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]
|
|
|
|
 |
|
 D. J. Lips, L. J. deWindt, D. J.W. van Kraaij, and P. A. Doevendans Molecular determinants of myocardial hypertrophy and failure: alternative pathways for beneficial and maladaptive hypertrophy Eur. Heart J., May 2, 2003; 24(10): 883 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Brittsan, K. S. Ginsburg, G. Chu, A. Yatani, B. M. Wolska, A. G. Schmidt, M. Asahi, D. H. MacLennan, D. M. Bers, and E. G. Kranias Chronic SR Ca2+-ATPase Inhibition Causes Adaptive Changes in Cellular Ca2+ Transport Circ. Res., April 18, 2003; 92(7): 769 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Dash, A. G Schmidt, A. Pathak, M. J Gerst, D. Biniakiewicz, V. J Kadambi, B. D Hoit, W. T Abraham, and E. G Kranias Differential regulation of p38 mitogen-activated protein kinase mediates gender-dependent catecholamine-induced hypertrophy Cardiovasc Res, March 1, 2003; 57(3): 704 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Semeniuk, D. L. Severson, A. J. Kryski, S. L. Swirp, J. D. Molkentin, and H. J. Duff Time-dependent systolic and diastolic function in mice overexpressing calcineurin Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H425 - H430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F Frank, B. Bolck, E. Erdmann, and R. H.G Schwinger Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation Cardiovasc Res, January 1, 2003; 57(1): 20 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhao, K. F Frank, G. Chu, M. J Gerst, A. G Schmidt, Y. Ji, M. Periasamy, and E. G Kranias Combined phospholamban ablation and SERCA1a overexpression result in a new hyperdynamic cardiac state Cardiovasc Res, January 1, 2003; 57(1): 71 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiomi, H. Tsutsui, S. Hayashidani, N. Suematsu, M. Ikeuchi, J. Wen, M. Ishibashi, T. Kubota, K. Egashira, and A. Takeshita Pioglitazone, a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction Circulation, December 10, 2002; 106(24): 3126 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G Schmidt, J. Zhai, A. N Carr, M. J Gerst, J. N Lorenz, P. Pollesello, A. Annila, B. D Hoit, and E. G Kranias Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure Cardiovasc Res, November 1, 2002; 56(2): 248 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Zingman, D. M. Hodgson, P. H. Bast, G. C. Kane, C. Perez-Terzic, R. J. Gumina, D. Pucar, M. Bienengraeber, P. P. Dzeja, T. Miki, et al. Kir6.2 is required for adaptation to stress PNAS, October 1, 2002; 99(20): 13278 - 13283. [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]
|
|
|
|
 |
|
 A. N. Carr, A. G. Schmidt, Y. Suzuki, F. del Monte, Y. Sato, C. Lanner, K. Breeden, S.-L. Jing, P. B. Allen, P. Greengard, et al. Type 1 Phosphatase, a Negative Regulator of Cardiac Function Mol. Cell. Biol., June 15, 2002; 22(12): 4124 - 4135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation Circ. Res., May 3, 2002; 90(8): 882 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Raidel, C. Haase, N. R. Jansen, R. B. Russ, R. L. Sutliff, L. W. Velsor, B. J. Day, B. D. Hoit, A. M. Samarel, and W. Lewis Targeted myocardial transgenic expression of HIV Tat causes cardiomyopathy and mitochondrial damage Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1672 - H1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kiriazis, Y. Sato, V. J Kadambi, A. G Schmidt, M. J Gerst, B. D Hoit, and E. G Kranias Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout mouse hearts under chronic aortic stenosis Cardiovasc Res, February 1, 2002; 53(2): 372 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Zwaal, K. Van Baelen, J. T. M. Groenen, A. van Geel, V. Rottiers, T. Kaletta, L. Dode, L. Raeymaekers, F. Wuytack, and T. Bogaert The Sarco-Endoplasmic Reticulum Ca2+ ATPase Is Required for Development and Muscle Function in Caenorhabditis elegans J. Biol. Chem., November 16, 2001; 276(47): 43557 - 43563. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. Dash, V. J. Kadambi, A. G. Schmidt, N. M. Tepe, D. Biniakiewicz, M. J. Gerst, A. M. Canning, W. T. Abraham, B. D. Hoit, S. B. Liggett, et al. Interactions Between Phospholamban and {{beta}}-Adrenergic Drive May Lead to Cardiomyopathy and Early Mortality Circulation, February 13, 2001; 103(6): 889 - 896. [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]
|
|
|
|
 |
|
 M. L. Marro, O. U. Scremin, M. C. Jordan, L. Huynh, F. Porro, K. P. Roos, S. Gajovic, F. E. Baralle, and A. F. Muro Hypertension in {beta}-Adducin-Deficient Mice Hypertension, September 1, 2000; 36(3): 449 - 453. [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]
|
|
|
|
|
|
E. Zvaritch, P. H. Backx, F. Jirik, Y. Kimura, S. de Leon, A. G. Schmidt, B. D. Hoit, J. W. Lester, E. G. Kranias, and D. H. MacLennan The Transgenic Expression of Highly Inhibitory Monomeric Forms of Phospholamban in Mouse Heart Impairs Cardiac Contractility J. Biol. Chem., May 12, 2000; 275(20): 14985 - 14991. [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]
|
|
|
|
|
|
J. Zhai, A. G. Schmidt, B. D. Hoit, Y. Kimura, D. H. MacLennan, and E. G. Kranias Cardiac-specific Overexpression of a Superinhibitory Pentameric Phospholamban Mutant Enhances Inhibition of Cardiac Function in Vivo J. Biol. Chem., March 31, 2000; 275(14): 10538 - 10544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, J. Desantiago, G. Chu, E. G. Kranias, and D. M. Bers Phosphorylation of phospholamban and troponin I in beta -adrenergic-induced acceleration of cardiac relaxation Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H769 - H779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Wiesmann, J. Ruff, K.-H. Hiller, E. Rommel, A. Haase, and S. Neubauer Developmental changes of cardiac function and mass assessed with MRI in neonatal, juvenile, and adult mice Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H652 - H657. [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]
|
|
|
|
 |
|
 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [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]
|
|
|
|
|
|
R. Prabhakar, G. P. Boivin, B. Hoit, and D. F. Wieczorek Rescue of High Expression beta -Tropomyosin Transgenic Mice by 5-Propyl-2-thiouracil. REGULATING THE alpha -MYOSIN HEAVY CHAIN PROMOTER J. Biol. Chem., October 8, 1999; 274(41): 29558 - 29563. [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]
|
|
|
|
|
|
U. Schmidt, R. J. Hajjar, C. S. Kim, D. Lebeche, A. A. Doye, and J. K. Gwathmey Human heart failure: cAMP stimulation of SR Ca2+-ATPase activity and phosphorylation level of phospholamban Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H474 - H480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sanbe, J. G. Fewell, J. Gulick, H. Osinska, J. Lorenz, D. G. Hall, L. A. Murray, T. R. Kimball, S. A. Witt, and J. Robbins Abnormal Cardiac Structure and Function in Mice Expressing Nonphosphorylatable Cardiac Regulatory Myosin Light Chain 2 J. Biol. Chem., July 23, 1999; 274(30): 21085 - 21094. [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]
|
|
|
|
 |
|
 Y.-Q. Xiong, L. I. Kupferwasser, P. M. Zack, and A. S. Bayer Comparative Efficacies of Liposomal Amikacin (MiKasome) plus Oxacillin versus Conventional Amikacin plus Oxacillin in Experimental Endocarditis Induced by Staphylococcus aureus: Microbiological and Echocardiographic Analyses Antimicrob. Agents Chemother., July 1, 1999; 43(7): 1737 - 1742. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. C Fentzke, S. H Buck, J. R Patel, H. Lin, B. M Wolska, M. O Stojanovic, A. F Martin, R J. Solaro, R. L Moss, and J. M Leiden Impaired cardiomyocyte relaxation and diastolic function in transgenic mice expressing slow skeletal troponin I in the heart J. Physiol., May 15, 1999; 517(1): 143 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Desai, E. Schauble, W. Luo, E. Kranias, and D. Bernstein Phospholamban deficiency does not compromise exercise capacity Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1172 - H1177. [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]
|
|
|
|
 |
|
 H. K. B. SIMMERMAN and L. R. JONES Phospholamban: Protein Structure, Mechanism of Action, and Role in Cardiac Function Physiol Rev, October 1, 1998; 78(4): 921 - 947. [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]
|
|
|
|
|
|
P. A Doevendans, M. J. Daemen, E. D de Muinck, and J. F Smits Cardiovascular phenotyping in mice Cardiovasc Res, July 1, 1998; 39(1): 34 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Hasenfuss Animal models of human cardiovascular disease, heart failure and hypertrophy Cardiovasc Res, July 1, 1998; 39(1): 60 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D Verdouw, M. A van den Doel, S. de Zeeuw, and D. J Duncker Animal models in the study of myocardial ischaemia and ischaemic syndromes Cardiovasc Res, July 1, 1998; 39(1): 121 - 135. [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]
|
|
|
|
|
|
Y. Sakata, B. D. Hoit, S. B. Liggett, R. A. Walsh, and G. W. Dorn II Decompensation of Pressure-Overload Hypertrophy in G{alpha}q-Overexpressing Mice Circulation, April 21, 1998; 97(15): 1488 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, G. Chu, E. G. Kranias, and D. M. Bers Cardiac myocyte calcium transport in phospholamban knockout mouse: relaxation and endogenous CaMKII effects Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1335 - H1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Luo, G. Chu, Y. Sato, Z. Zhou, V. J. Kadambi, and E. G. Kranias Transgenic Approaches to Define the Functional Role of Dual Site Phospholamban Phosphorylation J. Biol. Chem., February 20, 1998; 273(8): 4734 - 4739. [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]
|
|
|
|
|
|
J. N. Lorenz and E. G. Kranias Regulatory effects of phospholamban on cardiac function in intact mice Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2826 - H2831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Hoit, N. Ball, and R. A. Walsh Invasive hemodynamics and force-frequency relationships in open- versus closed-chest mice Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2528 - H2533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chu, G. W. Dorn II, W. Luo, J. M. Harrer, V. J. Kadambi, R. A. Walsh, and E. G. Kranias Monomeric Phospholamban Overexpression in Transgenic Mouse Hearts Circ. Res., October 19, 1997; 81(4): 485 - 492. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. Wakasaki, D. Koya, F. J. Schoen, M. R. Jirousek, D. K. Ways, B. D. Hoit, R. A. Walsh, and G. L. King Targeted overexpression of protein kinase C beta 2 isoform in myocardium causes cardiomyopathy PNAS, August 19, 1997; 94(17): 9320 - 9325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hajjar, U. Schmidt, J. X. Kang, T. Matsui, and A. Rosenzweig Adenoviral Gene Transfer of Phospholamban in Isolated Rat Cardiomyocytes : Rescue Effects by Concomitant Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase Circ. Res., August 19, 1997; 81(2): 145 - 153. [Abstract] [Full Text]
|
|
|
|
|
|
D. D. D'Angelo, Y. Sakata, J. N. Lorenz, G. P. Boivin, R. A. Walsh, S. B. Liggett, and G. W. Dorn II Transgenic Galpha q overexpression induces cardiac contractile failure in mice PNAS, July 22, 1997; 94(15): 8121 - 8126. [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]
|
|
|
|
|
|
K. L. Koss and E. G. Kranias Phospholamban: A Prominent Regulator of Myocardial Contractility Circ. Res., December 1, 1996; 79(6): 1059 - 1063. [Full Text]
|
|
|
|
|
|
S. F. Khoury, B. D. Hoit, V. Dave, C. M. Pawloski-Dahm, Y. Shao, M. Gabel, M. Periasamy, and R. A. Walsh Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca2+-Cycling Proteins in the Baboon: Implications for the Force-Frequency and Relaxation-Frequency Relationships Circ. Res., October 1, 1996; 79(4): 727 - 735. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Iwase, S. P. Bishop, M. Uechi, D. E. Vatner, R. P. Shannon, R. K. Kudej, D. C. Wight, T. E. Wagner, Y. Ishikawa, C. J. Homcy, et al. Adverse Effects of Chronic Endogenous Sympathetic Drive Induced by Cardiac Gs{alpha} Overexpression Circ. Res., April 1, 1996; 78(4): 517 - 524. [Abstract] [Full Text]
|
|
|
|
|
|
K. D. Becker, K. R. Gottshall, and K. R. Chien Strategies for Studying Cardiovascular Phenotypes in Genetically Manipulated Mice Hypertension, March 1, 1996; 27(3): 495 - 501. [Abstract] [Full Text]
|
|
|
|
|
|
G. Chu, J. W. Lester, K. B. Young, W. Luo, J. Zhai, and E. G. Kranias A Single Site (Ser16) Phosphorylation in Phospholamban Is Sufficient in Mediating Its Maximal Cardiac Responses to beta -Agonists J. Biol. Chem., December 1, 2000; 275(49): 38938 - 38943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Knollmann, S. A. Blatt, K. Horton, F. de Freitas, T. Miller, M. Bell, P. R. Housmans, N. J. Weissman, M. Morad, and J. D. Potter Inotropic Stimulation Induces Cardiac Dysfunction in Transgenic Mice Expressing a Troponin T (I79N) Mutation Linked to Familial Hypertrophic Cardiomyopathy J. Biol. Chem., March 23, 2001; 276(13): 10039 - 10048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Haghighi, A. G. Schmidt, B. D. Hoit, A. G. Brittsan, A. Yatani, J. W. Lester, J. Zhai, Y. Kimura, G. W. Dorn II, D. H. MacLennan, et al. Superinhibition of Sarcoplasmic Reticulum Function by Phospholamban Induces Cardiac Contractile Failure J. Biol. Chem., June 22, 2001; 276(26): 24145 - 24152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Wolska, G. M. Arteaga, J. R. Pena, G. Nowak, R. M. Phillips, S. Sahai, P. P. de Tombe, A. F. Martin, E. G. Kranias, and R. J. Solaro Expression of Slow Skeletal Troponin I in Hearts of Phospholamban Knockout Mice Alters the Relaxant Effect of {beta}-Adrenergic Stimulation Circ. Res., May 3, 2002; 90(8): 882 - 888. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||