Doppler Estimation of Reduced Coronary Flow Reserve in Mice with Pressure Overload Cardiac Hypertrophy

Hartley, Craig J.; Reddy, Anilkumar K.; Madala, Sridhar; Michael, Lloyd H.; Entman, Mark L.; Taffet, George E.

doi:10.1016/j.ultrasmedbio.2007.11.019

Cited by 47 publications

(52 citation statements)

References 45 publications

(93 reference statements)

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“…As a coronary vasodilator stimulus, the inhaled isoflurane concentration was increased to 2.5%. The coronary vasodilatory properties of isoflurane in general are well described (47), and we have previously validated its use in the measurement of CFR in conjunction with a noninvasive ultrasound technique (33,48). Ratios of peak velocities at low-(1%) and high-dose (2.5%) isoflurane were reported as CFR.…”

Section: Methodsmentioning

confidence: 98%

“…Carotid velocities were measured 24 hours, 7 days, and 14 days after TAC using a 20-Mhz ultrasound probe connected to a signal processing unit (Indus Instruments) using our previously published protocol (46). CFR was measured as previously described (33). Briefly, the ultrasound probe tip was placed at the left side of the chest of the anesthetized animal and stabilized using a micromanipulator (model MM3-3, World Precision Instruments).…”

Section: Methodsmentioning

confidence: 99%

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Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

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175

140

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PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-β expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to loadinduced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-β signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-β was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-β is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors.

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Section: Methodsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Chintalgattu¹,

Ai²,

Langley³

et al. 2010

J. Clin. Invest.

Self Cite

175

140

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show abstract

“…Measures of coronary velocity reserve under conditions of hypoxia (55), hypertrophy after aortic banding (TAC) (26), and vasodilatation (isoflurane inhalation) (27) have enabled the assessment of coronary microdysfunction during early and late pathological changes in the development of atherosclerosis and heart failure. In myocardial contrast echocardiography, contrast microbubbles agents filled with inert gas reflect sound waves returning to the transducer with increased signal-tonoise ratio.…”

Section: Myocardial Perfusion Assessmentmentioning

confidence: 99%

New approaches in small animal echocardiography: imaging the sounds of silence

Ram

Mickelsen

Theodoropoulos

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

117

132

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Systolic and diastolic dysfunction of the left ventricle (LV) is a hallmark of most cardiac diseases. In vivo assessment of heart function in animal models, particularly mice, is essential to refining our understanding of cardiovascular disease processes. Ultrasound echocardiography has emerged as a powerful, noninvasive tool to serially monitor cardiac performance and map the progression of heart dysfunction in murine injury models. This review covers current applications of small animal echocardiography, as well as emerging technologies that improve evaluation of LV function. In particular, we describe speckle-tracking imaging-based regional LV analysis, a recent advancement in murine echocardiography with proven clinical utility. This sensitive measure enables an early detection of subtle myocardial defects before global dysfunction in genetically engineered and rodent surgical injury models. Novel visualization technologies that allow in-depth phenotypic assessment of small animal models, including perfusion imaging and fetal echocardiography, are also discussed. As imaging capabilities continue to improve, murine echocardiography will remain a critical component of the investigator's armamentarium in translating animal data to enhanced clinical treatment of cardiovascular diseases. murine echocardiography; systolic and diastolic function; speckle-tracking imaging; strain analysis; heart failure THIS ARTICLE is part of a collection on Assessing Cardiovascular Function in Mice: New Developments and Methods. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.Rodents are invaluable models for cardiovascular research, in part because of the extensive knowledge of their genome, homogeneity of study population, reproducible pathological phenotypes, and relative ease of creating genetically modified models. Surgical techniques that induce myocardial overload, infarction, and dysfunction in mice and rats have enabled a reliable identification and assessment of key physiological, molecular, and biochemical mechanisms of cardiovascular diseases (43). With the use of noninvasive imaging tools such as ultrasound echocardiography, cardiovascular evaluation of rodents has further led to the translational development of new diagnostic techniques and therapeutic strategies to predict and prevent cardiovascular disease complications in humans (82).Echocardiography remains a gold standard for a reliable assessment of cardiovascular structure and function in humans (19). The technology's allure lies primarily in its portability, relative affordability, widespread availability, noninvasive nature, and rapid real-time imaging capabilities. With advancements in clinical echocardiography, the technicalities and conceptual framework of the methodology and equipment have been extended from humans to small animals. Ultrasound imaging greatly facilitates the evaluation of cardiac function in transgenic animals, as well as surgically induced ...

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“…Using the above procedure, we estimated left main CFR in 10 mice before and at several time points for 21 days after TAC (23). Figure 5 shows waveforms at baseline and at hyperemia from one mouse before, 1 day after, and 21 days after TAC.…”

Section: Coronary Flow Reservementioning

confidence: 99%

“…We will focus here on noninvasive ultrasonic Doppler methods, which our group and others have developed and used to evaluate cardiovascular physiology and function in anesthetized mice and which can be used serially to follow changes because of aging, remodeling, and/or the effects of surgical or pharmacological interventions (19,66). The utility and value of the measurements will be illustrated using the widely used model of transverse aortic constriction (TAC) that was developed for producing pressure-overload cardiac hypertrophy and remodeling (51) but which produces numerous other measurable changes in peripheral vascular mechanics and function (23,34). …”

mentioning

confidence: 99%

Doppler velocity measurements from large and small arteries of mice

Hartley

Reddy

Madala

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Hartley CJ, Reddy AK, Madala S, Entman ML, Michael LH, Taffet GE. Doppler velocity measurements from large and small arteries of mice. Am J Physiol Heart Circ Physiol 301: H269 -H278, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00320.2011With the growth of genetic engineering, mice have become increasingly common as models of human diseases, and this has stimulated the development of techniques to assess the murine cardiovascular system. Our group has developed nonimaging and dedicated Doppler techniques for measuring blood velocity in the large and small peripheral arteries of anesthetized mice. We translated technology originally designed for human vessels for use in smaller mouse vessels at higher heart rates by using higher ultrasonic frequencies, smaller transducers, and higher-speed signal processing. With these methods one can measure cardiac filling and ejection velocities, velocity pulse arrival times for determining pulse wave velocity, peripheral blood velocity and vessel wall motion waveforms, jet velocities for the calculation of the pressure drop across stenoses, and left main coronary velocity for the estimation of coronary flow reserve. These noninvasive methods are convenient and easy to apply, but care must be taken in interpreting measurements due to Doppler sample volume size and angle of incidence. Doppler methods have been used to characterize and evaluate numerous cardiovascular phenotypes in mice and have been particularly useful in evaluating the cardiac and vascular remodeling that occur following transverse aortic constriction. Although duplex ultrasonic echo-Doppler instruments are being applied to mice, dedicated Doppler systems are more suitable for some applications. The magnitudes and waveforms of blood velocities from both cardiac and peripheral sites are similar in mice and humans, such that much of what is learned using Doppler technology in mice may be translated back to humans. peripheral vascular flow; pulse wave velocity; coronary flow reserve; transverse aortic constriction; pressure overload hypertrophy THIS REVIEW ARTICLE is part of a collection on Assessing Cardiovascular Function in Mice: New Developments and Methods. Other articles appearing in this collection, as well as a full archive of all Review collections, can be found online at http://ajpheart.physiology.org/.The ability to alter the genotype of the mouse has produced numerous models for studying cardiovascular physiology and pathophysiology and has generated a need to evaluate the changes that occur in mice during phenotypic development and maturation (8). The genetic manipulations can alter the structure, anatomy, pathology, and physiology of cells, organs, or systems in ways that can be subtle and unpredictable and that often change with time (6, 33). The major problems in adapting existing methods for use in mice relate to the small size and high heart rates that place extreme demands on both spatial and temporal resolution (10). We will focus here on noninvasive ultrasonic Doppler methods, w...

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Doppler Estimation of Reduced Coronary Flow Reserve in Mice with Pressure Overload Cardiac Hypertrophy

Cited by 47 publications

References 45 publications

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

Cardiomyocyte PDGFR-β signaling is an essential component of the mouse cardiac response to load-induced stress

New approaches in small animal echocardiography: imaging the sounds of silence

Doppler velocity measurements from large and small arteries of mice

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