Echocardiographic evaluation of diastolic function in mouse models of heart disease
Moritz Schnelle, Norman Catibog, Min Zhang, Adam A Nabeebaccus, Grace Anderson, Daniel A Richards, Greta Sawyer, Xiaohong Zhang, Karl Toischer, Gerd Hasenfuss, Mark J Monaghan, Ajay M Shah, Moritz Schnelle, Norman Catibog, Min Zhang, Adam A Nabeebaccus, Grace Anderson, Daniel A Richards, Greta Sawyer, Xiaohong Zhang, Karl Toischer, Gerd Hasenfuss, Mark J Monaghan, Ajay M Shah
Abstract
Background: Mouse models of heart disease are extensively employed. The echocardiographic characterization of contractile function is usually focused on systolic function with fewer studies assessing diastolic function. Furthermore, the applicability of diverse echocardiographic parameters of diastolic function that are commonly used in humans has not been extensively evaluated in different pathophysiological models in mice.
Methods and results: We used high resolution echocardiography to evaluate parameters of diastolic function in mouse models of chronic pressure overload (aortic constriction), volume overload (aorto-caval shunt), heart failure with preserved ejection fraction (HFpEF; DOCA-salt hypertension), and acute sarcoplasmic reticulum dysfunction induced by thapsigargin - all known to exhibit diastolic dysfunction. Left atrial area increased in all three chronic models while mitral E/A was difficult to quantify at high heart rates. Isovolumic relaxation time (IVRT) and Doppler E/E' increased significantly and the peak longitudinal strain rate during early filling (peak reverse longitudinal strain rate) decreased significantly after aortic constriction, with the changes being proportional to the magnitude of hypertrophy. In the HFpEF model, reverse longitudinal strain rate decreased significantly but changes in IVRT and E/E' were non-significant, consistent with less severe dysfunction. With volume overload, there was a significant increase in reverse longitudinal strain rate and decrease in IVRT, indicating a restrictive physiology. Acute thapsigargin treatment caused significant prolongation of IVRT and decrease in reverse longitudinal strain rate.
Conclusion: These results indicate that the combined measurement of left atrial area plus reverse longitudinal strain rate and/or IVRT provide an excellent overall assessment of diastolic function in the diseased mouse heart, allowing distinction between different types of pathophysiology.
Keywords: Diastolic function; Echocardiography; Hypertrophy; Mouse.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Figures
References
- Zile M.R., Baicu C.F., Gaasch W.H. Diastolic heart failure - abnormalities in active relaxation and passive stiffness of the left ventricle. N. Engl. J. Med. 2004;350:1953–1959.
- Udelson J.E. Heart failure with preserved ejection fraction. Circulation. 2011;124:e540–e543.
- Borlaug B.A. The pathophysiology of heart failure with preserved ejection fraction. Nat. Rev. Cardiol. 2014;11:507–515.
- Nagueh S.F., Smiseth O.A., Appleton C.P., Byrd B.F., Dokainish H., Edvardsen T. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J. Am. Soc. Echocardiogr. 2016;29:277–314.
- Oh J.K., Appleton C.P., Hatle L.K., Nishimura R.A., Seward J.B., Tajik A.J. The noninvasive assessment of left ventricular diastolic function with two-dimensional and doppler echocardiography. J. Am. Soc. Echocardiogr. 1997;10:246–270.
- Ommen S.R., Nishimura R.A., Appleton C.P., Miller F.A., Oh J.K., Redfield M.M. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous doppler-catheterization study. Circulation. 2000;102:1788–1794.
- Byrne J.A., Grieve D.J., Bendall J.K., Li J.M., Gove C., Lambeth J.D. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ. Res. 2003;93:802–805.
- Martin T.P., Robinson E., Harvey A.P., MacDonald M., Grieve D.J., Paul A. Surgical optimization and characterization of a minimally invasive aortic banding procedure to induce cardiac hypertrophy in mice. Exp. Physiol. 2012;97:822–832.
- Toischer K., Rokita A.G., Unsold B., Zhu W., Kararigas G., Sossalla S. Differential cardiac remodeling in preload versus afterload. Circulation. 2010;122:993–1003.
- Silberman G.A., Fan T.H., Liu H., Jiao Z., Xiao H.D., Lovelock J.D. Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation. 2010;121:519–528.
- Thastrup O., Cullen P.J., Drobak B.K., Hanley M.R., Dawson A.P. Thapsigargin, a tumor promoter, discharges intracellular Ca2 + stores by specific inhibition of the endoplasmic reticulum Ca2 +-ATPase. Proc. Natl. Acad. Sci. U. S. A. 1990;87:2466–2470.
- Bhan A., Sirker A., Zhang J., Protti A., Catibog N., Driver W. High-frequency speckle tracking echocardiography in the assessment of left ventricular function and remodeling after murine myocardial infarction. Am. J. Phys. 2014;306:H1371–H1383.
- Zhang M., Prosser B.L., Bamboye M.A., Gondim A.N., Santos C.X., Martin D. Contractile function during angiotensin-II activation: increased Nox2 activity modulates cardiac calcium handling via phospholamban phosphorylation. J. Am. Coll. Cardiol. 2015;66:261–272.
- Abhayaratna W.P., Seward J.B., Appleton C.P., Douglas P.S., Oh J.K., Tajik A.J. Left atrial size: physiologic determinants and clinical applications. J. Am. Coll. Cardiol. 2006;47:2357–2363.
- Oh J.K., Park S.J., Nagueh S.F. Established and novel clinical applications of diastolic function assessment by echocardiography. Circ. Cardiovasc. Imaging. 2011;4:444–455.
- Paulus W.J., Tschope C., Sanderson J.E., Rusconi C., Flachskampf F.A., Rademakers F.E. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur. Heart J. 2007;28:2539–2550.
- Li Y., Charles P.Y., Nan C., Pinto J.R., Wang Y., Liang J. Correcting diastolic dysfunction by Ca2 + desensitizing troponin in a transgenic mouse model of restrictive cardiomyopathy. J. Mol. Cell. Cardiol. 2010;49:402–411.
- Li Y., Zhang L., Jean-Charles P.Y., Nan C., Chen G., Tian J. Dose-dependent diastolic dysfunction and early death in a mouse model with cardiac troponin mutations. J. Mol. Cell. Cardiol. 2013;62:227–236.
- Wang J., Khoury D.S., Thohan V., Torre-Amione G., Nagueh S.F. Global diastolic strain rate for the assessment of left ventricular relaxation and filling pressures. Circulation. 2007;115:1376–1383.
- Maurer M.S., Spevack D., Burkhoff D., Kronzon I. Diastolic dysfunction: can it be diagnosed by Doppler echocardiography? J. Am. Coll. Cardiol. 2004;44:1543–1549.
- Fraysse B., Weinberger F., Bardswell S.C., Cuello F., Vignier N., Geertz B. Increased myofilament Ca2 + sensitivity and diastolic dysfunction as early consequences of MyBPC3 mutation in heterozygous knock-in mice. J. Mol. Cell. Cardiol. 2012;52:1299–1307.
- Zhang L., Jaswal J.S., Ussher J.R., Sankaralingam S., Wagg C., Zaugg M. Cardiac insulin-resistance and decreased mitochondrial energy production precede the development of systolic heart failure after pressure-overload hypertrophy. Circ. Heart Fail. 2013;6:1039–1048.
- Szardien S., Nef H.M., Voss S., Troidl C., Liebetrau C., Hoffmann J. Regression of cardiac hypertrophy by granulocyte colony-stimulating factor-stimulated interleukin-1beta synthesis. Eur. Heart J. 2012;33:595–605.
- Tsang T.S., Barnes M.E., Gersh B.J., Bailey K.R., Seward J.B. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am. J. Cardiol. 2002;90:1284–1289.
- Gonzalez-Quesada C., Cavalera M., Biernacka A., Kong P., Lee D.W., Saxena A. Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix in addition to promoting vascular rarefaction through angiopoietin-2 upregulation. Circ. Res. 2013;113:1331–1344.
- Yoshida C., Nakao S., Goda A., Naito Y., Matsumoto M., Otsuka M. Value of assessment of left atrial volume and diameter in patients with heart failure but with normal left ventricular ejection fraction and mitral flow velocity pattern. Eur. J. Echocardiogr. 2009;10:278–281.
- Erkens R., Kramer C.M., Luckstadt W., Panknin C., Krause L., Weidenbach M. Left ventricular diastolic dysfunction in NRF2 knock out mice is associated with cardiac hypertrophy, decreased expression of Serca2a, and preserved endothelial function. Free Radic. Biol. Med. 2015;89(215):906–917.
- Roth D.M., Swaney J.S., Dalton N.D., Gilpin E.A., EA Ross J., Jr. Impact of anesthesia on cardiac function during echocardiography in mice. Am. J. Phys. 2002;282:H2134–H 2140.
Source: PubMed