Skip to main content
Top
Published in: The International Journal of Cardiovascular Imaging 9/2019

01-09-2019 | Magnetic Resonance Imaging | Original Paper

Comprehensive cardiac phenotyping in large animals: comparison of pressure–volume analysis and cardiac magnetic resonance imaging in pig post-myocardial infarction systolic heart failure

Authors: Philip W. J. Raake, Jens Barthelmes, Birgit Krautz, Sebastian Buss, Regina Huditz, Philipp Schlegel, Christophe Weber, Manfred Stangassinger, Uwe Haberkorn, Hugo A. Katus, Patrick Most, Sven T. Pleger

Published in: The International Journal of Cardiovascular Imaging | Issue 9/2019

Login to get access

Abstract

Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload–insensitive parameters show high sensitivity to quantify HF while preload–sensitive parameters are not able to quantify early-stages of LV HF.
Literature
1.
go back to reference Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O’Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P (2018) Heart Disease and Stroke Statistics - 2018 Update: a Report from the American Heart Association. Circulation 137(12):e67–e492CrossRefPubMed Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O’Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P (2018) Heart Disease and Stroke Statistics - 2018 Update: a Report from the American Heart Association. Circulation 137(12):e67–e492CrossRefPubMed
4.
go back to reference Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM (2008) Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Ther 15(23):1550–1557CrossRefPubMed Byrne MJ, Power JM, Preovolos A, Mariani JA, Hajjar RJ, Kaye DM (2008) Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals. Gene Ther 15(23):1550–1557CrossRefPubMed
5.
go back to reference Dixon JA, Spinale FG (2009) Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail 2:262–271CrossRefPubMedPubMedCentral Dixon JA, Spinale FG (2009) Large animal models of heart failure: a critical link in the translation of basic science to clinical practice. Circ Heart Fail 2:262–271CrossRefPubMedPubMedCentral
6.
go back to reference Lai NC, Roth DM, Gao MH, Tang T, Dalton N, Lai YY, Spellman M, Clopton P, Hammond HK (2004) Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110(3):330–336CrossRefPubMed Lai NC, Roth DM, Gao MH, Tang T, Dalton N, Lai YY, Spellman M, Clopton P, Hammond HK (2004) Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110(3):330–336CrossRefPubMed
7.
go back to reference Pleger ST, Boucher M, Most P, Koch WJ (2007) Targeting myocardial beta-adrenergic receptor signaling and calcium cycling for heart failure gene therapy. J Card Fail 13(5):401–414CrossRefPubMed Pleger ST, Boucher M, Most P, Koch WJ (2007) Targeting myocardial beta-adrenergic receptor signaling and calcium cycling for heart failure gene therapy. J Card Fail 13(5):401–414CrossRefPubMed
8.
go back to reference Pleger ST, Shan C, Ksienzyk J, Bekeredjian R, Boekstegers P, Hinkel R, Schinkel S, Leuchs B, Ludwig J, Qiu G, Weber C, Raake P, Koch WJ, Katus HA, Müller OJ, Most P (2011) Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci Transl Med 3(92):92ra64CrossRefPubMedPubMedCentral Pleger ST, Shan C, Ksienzyk J, Bekeredjian R, Boekstegers P, Hinkel R, Schinkel S, Leuchs B, Ludwig J, Qiu G, Weber C, Raake P, Koch WJ, Katus HA, Müller OJ, Most P (2011) Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci Transl Med 3(92):92ra64CrossRefPubMedPubMedCentral
9.
go back to reference Raake PW, Schlegel P, Ksienzyk J, Reinkober J, Barthelmes J, Schinkel S, Pleger S, Mier W, Haberkorn U, Koch WJ, Katus HA, Most P, Müller OJ (2013) AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 34(19):1437–1447CrossRefPubMed Raake PW, Schlegel P, Ksienzyk J, Reinkober J, Barthelmes J, Schinkel S, Pleger S, Mier W, Haberkorn U, Koch WJ, Katus HA, Most P, Müller OJ (2013) AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 34(19):1437–1447CrossRefPubMed
10.
go back to reference Lin HY, Freed D, Lee TW, Arora RC, Ali A, Almoustadi W, Xiang B, Wang F, Large S, King SB, Tomanek B, Tian G (2011) Quantitative assessment of cardiac output and left ventricular function by noninvasive phase-contrast and cine MRI: validation study with invasive pressure-volume loop analysis in a swine model. J Magn Reson Imaging 34(1):203–210CrossRefPubMed Lin HY, Freed D, Lee TW, Arora RC, Ali A, Almoustadi W, Xiang B, Wang F, Large S, King SB, Tomanek B, Tian G (2011) Quantitative assessment of cardiac output and left ventricular function by noninvasive phase-contrast and cine MRI: validation study with invasive pressure-volume loop analysis in a swine model. J Magn Reson Imaging 34(1):203–210CrossRefPubMed
11.
go back to reference Van Hout GP, Jansen of Lorkeers SJ, Gho JM, Doevendans PA, van Solinge WW, Pasterkamp G, Chamuleau SA, Hoefer IE (2014) Admittance-based pressure-volume loops versus gold standard cardiac magnetic resonance imaging in a porcine model of myocardial infarction. Physiol Rep 2(4):e00287CrossRefPubMedPubMedCentral Van Hout GP, Jansen of Lorkeers SJ, Gho JM, Doevendans PA, van Solinge WW, Pasterkamp G, Chamuleau SA, Hoefer IE (2014) Admittance-based pressure-volume loops versus gold standard cardiac magnetic resonance imaging in a porcine model of myocardial infarction. Physiol Rep 2(4):e00287CrossRefPubMedPubMedCentral
12.
go back to reference Licka M, Zimmermann R, Zehelein J, Dengler TJ, Katus HA, Kübler W (2002) Troponin T concentrations 72 hours after myocardial infarction as a serological estimate of infarct size. Heart 87(6):520–524CrossRefPubMedPubMedCentral Licka M, Zimmermann R, Zehelein J, Dengler TJ, Katus HA, Kübler W (2002) Troponin T concentrations 72 hours after myocardial infarction as a serological estimate of infarct size. Heart 87(6):520–524CrossRefPubMedPubMedCentral
13.
go back to reference Cingolani OH, Kass DA (2011) Pressure-volume relation analysis of mouse ventricular function. Am J Physiol Heart Circ Physiol 301(6):H2198–H2206CrossRefPubMed Cingolani OH, Kass DA (2011) Pressure-volume relation analysis of mouse ventricular function. Am J Physiol Heart Circ Physiol 301(6):H2198–H2206CrossRefPubMed
14.
go back to reference Burkhoff D, Mirsky I, Suga H (2005) Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers. Am J Physiol Heart Circ Physiol 289(2):H501–H512CrossRefPubMed Burkhoff D, Mirsky I, Suga H (2005) Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers. Am J Physiol Heart Circ Physiol 289(2):H501–H512CrossRefPubMed
15.
go back to reference Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1(8476):307–310CrossRefPubMed Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1(8476):307–310CrossRefPubMed
16.
go back to reference Tilemann L, Ishikawa K, Weber T, Hajjar RJ (2012) Gene therapy for heart failure. Circ Res 10(5):777–793CrossRef Tilemann L, Ishikawa K, Weber T, Hajjar RJ (2012) Gene therapy for heart failure. Circ Res 10(5):777–793CrossRef
17.
go back to reference Steen H, Nasir K, Flynn E, El-Shehaby I, Lai S, Katus HA, Bluemcke D, Lima JA (2007) Is magnetic resonance imaging the ‘reference standard’ for cardiac functional assessment? Factors influencing measurement of left ventricular mass and volumes. Clin Res Cardiol 96(10):743–751CrossRefPubMed Steen H, Nasir K, Flynn E, El-Shehaby I, Lai S, Katus HA, Bluemcke D, Lima JA (2007) Is magnetic resonance imaging the ‘reference standard’ for cardiac functional assessment? Factors influencing measurement of left ventricular mass and volumes. Clin Res Cardiol 96(10):743–751CrossRefPubMed
18.
go back to reference Yilmaz A, Ferreira V, Klingel K, Kandolf R, Neubauer S, Sechtem U (2013) Role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis of acute and chronic myocarditis. Heart Fail Rev 18(6):747–760CrossRefPubMed Yilmaz A, Ferreira V, Klingel K, Kandolf R, Neubauer S, Sechtem U (2013) Role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis of acute and chronic myocarditis. Heart Fail Rev 18(6):747–760CrossRefPubMed
Metadata
Title
Comprehensive cardiac phenotyping in large animals: comparison of pressure–volume analysis and cardiac magnetic resonance imaging in pig post-myocardial infarction systolic heart failure
Authors
Philip W. J. Raake
Jens Barthelmes
Birgit Krautz
Sebastian Buss
Regina Huditz
Philipp Schlegel
Christophe Weber
Manfred Stangassinger
Uwe Haberkorn
Hugo A. Katus
Patrick Most
Sven T. Pleger
Publication date
01-09-2019
Publisher
Springer Netherlands
Published in
The International Journal of Cardiovascular Imaging / Issue 9/2019
Print ISSN: 1569-5794
Electronic ISSN: 1875-8312
DOI
https://doi.org/10.1007/s10554-019-01610-z

Other articles of this Issue 9/2019

The International Journal of Cardiovascular Imaging 9/2019 Go to the issue