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Erschienen in: Journal of Nuclear Cardiology 2/2020

18.11.2019 | Original Article

Functional significance of post-myocardial infarction inflammation evaluated by 18F-fluorodeoxyglucose imaging in swine model

verfasst von: Xiao-Ying Xi, MD, Feifei Zhang, MD, Jianfeng Wang, MD, Wei Gao, MD, Yi Tian, MD, Hongyu Xu, MD, Min Xu, MD, Yuetao Wang, MD, Min-Fu Yang, MD

Erschienen in: Journal of Nuclear Cardiology | Ausgabe 2/2020

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Abstract

Background

The aim of the study was to investigate the relationship between post-myocardial infarction (MI) inflammation and left ventricular (LV) remodeling in a swine model by 18F-fluorodeoxyglucose (FDG) imaging.

Methods

MI was induced in swine by balloon occlusion of the left anterior descending coronary artery. A series of FDG positron emission tomography (PET) images were taken within 2 weeks post-MI, employing a comprehensive strategy to suppress the physiological uptake of cardiomyocytes. Echocardiography was applied to evaluate LV volume, global and regional function. CD68+ macrophage and glucose transporters (GLUT-1, -3 and -4) were investigated by immunostaining.

Results

The physiological uptake of myocardium was adequately suppressed in 92.3% of PET scans verified by visual analysis, which was further confirmed by the minimal expression of myocardial GLUT-4. Higher FDG uptake was observed in the infarct than in the remote area and persisted within the observational period of 2 weeks. The FDG uptake of infarcted myocardium on day 1 post-MI was correlated with LV global remodeling, and the FDG uptake of infarcted myocardium on days 1 and 8 post-MI had a trend of correlating with regional remodeling of the infarct area.

Conclusions

We here report a feasible swine model for investigating post-MI inflammation. FDG signal in the infarct area of swine persisted for a longer duration than has been reported in small animals. FDG activity in the infarct area could predict LV remodeling.
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Literatur
1.
Zurück zum Zitat Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 2011;17:581-8.CrossRef Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, et al. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med 2011;17:581-8.CrossRef
2.
Zurück zum Zitat Jung K, Kim P, Leuschner F, Gorbatov R, Kim JK, Ueno T, et al. Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res 2013;112:891-9.CrossRef Jung K, Kim P, Leuschner F, Gorbatov R, Kim JK, Ueno T, et al. Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res 2013;112:891-9.CrossRef
3.
Zurück zum Zitat Majmudar MD, Keliher EJ, Heidt T, Leuschner F, Truelove J, Sena BF, et al. Monocyte-directed RNAi targeting CCR3 improves infarct healing in atherosclerosis-prone mice. Circulation 2013;127:2038-46.CrossRef Majmudar MD, Keliher EJ, Heidt T, Leuschner F, Truelove J, Sena BF, et al. Monocyte-directed RNAi targeting CCR3 improves infarct healing in atherosclerosis-prone mice. Circulation 2013;127:2038-46.CrossRef
4.
Zurück zum Zitat Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 2013;339:161-6.CrossRef Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 2013;339:161-6.CrossRef
5.
Zurück zum Zitat Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64.CrossRef Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64.CrossRef
6.
Zurück zum Zitat Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: Protagonists of infarct inflammation and repair after myocardial infarction. Circulation 2010;121:2437-45.CrossRef Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: Protagonists of infarct inflammation and repair after myocardial infarction. Circulation 2010;121:2437-45.CrossRef
7.
Zurück zum Zitat Van der Laan AM, Ter Horst EN, Delewi R, Begieneman MP, Krijnen PA, Hirsch A, et al. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J 2014;35:376-85.CrossRef Van der Laan AM, Ter Horst EN, Delewi R, Begieneman MP, Krijnen PA, Hirsch A, et al. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur Heart J 2014;35:376-85.CrossRef
8.
Zurück zum Zitat Dimitrijević O, Stojcevski BD, Ignjatović S, Singh NM. Serial measurements of C-reactive protein after acute myocardial infarction in predicting one-year outcome. Int Heart J 2006;47:833-42.CrossRef Dimitrijević O, Stojcevski BD, Ignjatović S, Singh NM. Serial measurements of C-reactive protein after acute myocardial infarction in predicting one-year outcome. Int Heart J 2006;47:833-42.CrossRef
9.
Zurück zum Zitat Prondzinsky R, Unverzagt S, Lemm H, Wegener NA, Schlitt A, Heinroth KM, et al. Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res in Cardiol 2012;101:375-84.CrossRef Prondzinsky R, Unverzagt S, Lemm H, Wegener NA, Schlitt A, Heinroth KM, et al. Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock. Clin Res in Cardiol 2012;101:375-84.CrossRef
10.
Zurück zum Zitat White DA, Su Y, Kanellakis P, Kiriazis H, Morand EF, Bucala R, et al. Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction. J Mol Cell Cardiol 2014;69:32-42.CrossRef White DA, Su Y, Kanellakis P, Kiriazis H, Morand EF, Bucala R, et al. Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction. J Mol Cell Cardiol 2014;69:32-42.CrossRef
11.
Zurück zum Zitat Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, et al. Targeting post-infarct inflammation by PET imaging: Comparison of (68) Ga-citrate and (68) Ga-DOTATATE with (18) F-FDG in a mouse model. Eur J Nucl Med Mol Imaging 2015;42:317-27.CrossRef Thackeray JT, Bankstahl JP, Wang Y, Korf-Klingebiel M, Walte A, Wittneben A, et al. Targeting post-infarct inflammation by PET imaging: Comparison of (68) Ga-citrate and (68) Ga-DOTATATE with (18) F-FDG in a mouse model. Eur J Nucl Med Mol Imaging 2015;42:317-27.CrossRef
12.
Zurück zum Zitat Lee WW, Marinelli B, van der Laan AM, Sena BF, Gorbatov R, Leuschner F, et al. PET/MRI of inflammation in myocardial infarction. J Am Coll Cardiol 2012;59:153-63.CrossRef Lee WW, Marinelli B, van der Laan AM, Sena BF, Gorbatov R, Leuschner F, et al. PET/MRI of inflammation in myocardial infarction. J Am Coll Cardiol 2012;59:153-63.CrossRef
13.
Zurück zum Zitat Rischpler C, Dirschinger RJ, Nekolla SG, Kossmann H, Nicolosi S, Hanus F, et al. Prospective evaluation of 18F-Fluorodeoxyglucose uptake in postischemic myocardium by simultaneous positron emission tomography/magnetic resonance imaging as a prognostic marker of functional outcome. Circ Cardiovasc Imaging. 2016;9:e004316.CrossRef Rischpler C, Dirschinger RJ, Nekolla SG, Kossmann H, Nicolosi S, Hanus F, et al. Prospective evaluation of 18F-Fluorodeoxyglucose uptake in postischemic myocardium by simultaneous positron emission tomography/magnetic resonance imaging as a prognostic marker of functional outcome. Circ Cardiovasc Imaging. 2016;9:e004316.CrossRef
14.
Zurück zum Zitat Wollenweber T, Roentgen P, Schäfer A, Schatka I, Zwadlo C, Brunkhorst T, et al. Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging. Circ Cardiovasc Imaging 2014;7:811-8.CrossRef Wollenweber T, Roentgen P, Schäfer A, Schatka I, Zwadlo C, Brunkhorst T, et al. Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging. Circ Cardiovasc Imaging 2014;7:811-8.CrossRef
15.
Zurück zum Zitat Osborne MT, Hulten EA, Murthy VL, Skali H, Taqueti VR, Dorbala S, et al. Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. J Nucl Cardiol 2017;24:86-99.CrossRef Osborne MT, Hulten EA, Murthy VL, Skali H, Taqueti VR, Dorbala S, et al. Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. J Nucl Cardiol 2017;24:86-99.CrossRef
16.
Zurück zum Zitat Romito E, Shazly T, Spinale FG. In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead. J Appl Physiol 2017;123:728-45.CrossRef Romito E, Shazly T, Spinale FG. In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead. J Appl Physiol 2017;123:728-45.CrossRef
17.
Zurück zum Zitat Chan W, Duffy SJ, White DA, Gao XM, Du XJ, Ellims AH, et al. Acute left ventricular remodeling following myocardial infarction: Coupling of regional healing with remote extracellular matrix expansion. JACC Cardiovasc Imaging 2012;5:884-93.CrossRef Chan W, Duffy SJ, White DA, Gao XM, Du XJ, Ellims AH, et al. Acute left ventricular remodeling following myocardial infarction: Coupling of regional healing with remote extracellular matrix expansion. JACC Cardiovasc Imaging 2012;5:884-93.CrossRef
18.
Zurück zum Zitat Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M, et al. Pathophysiology of LV remodeling in survivors of STEMI: Inflammation, remote myocardium, and prognosis. JACC Cardiovasc Imaging 2015;8:779-89.CrossRef Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M, et al. Pathophysiology of LV remodeling in survivors of STEMI: Inflammation, remote myocardium, and prognosis. JACC Cardiovasc Imaging 2015;8:779-89.CrossRef
19.
Zurück zum Zitat Reinstadler SJ, Stiermaier T, Liebetrau J, Fuernau G, Eitel C, de Waha S, et al. Prognostic significance of remote myocardium alterations assessed by quantitative noncontrast T1 mapping in ST-segment elevation myocardial infarction. JACC Cardiovasc Imaging 2018;11:411-9.CrossRef Reinstadler SJ, Stiermaier T, Liebetrau J, Fuernau G, Eitel C, de Waha S, et al. Prognostic significance of remote myocardium alterations assessed by quantitative noncontrast T1 mapping in ST-segment elevation myocardial infarction. JACC Cardiovasc Imaging 2018;11:411-9.CrossRef
20.
Zurück zum Zitat Puntmann VO, Carr-White G, Jabbour A, Yu CY, Gebker R, Kelle S, et al. Native T1 and ECV of noninfarcted myocardium and outcome in patients with coronary artery disease. J Am Cool Cardiol 2018;71:766-78.CrossRef Puntmann VO, Carr-White G, Jabbour A, Yu CY, Gebker R, Kelle S, et al. Native T1 and ECV of noninfarcted myocardium and outcome in patients with coronary artery disease. J Am Cool Cardiol 2018;71:766-78.CrossRef
21.
Zurück zum Zitat McCall FC, Telukuntla KS, Karantalis V, Suncion VY, Heldman AW, Mushtag M, et al. Myocardial infarction and intramyocardial injection models in swine. Nat Protoc 2012;7:1479-96.CrossRef McCall FC, Telukuntla KS, Karantalis V, Suncion VY, Heldman AW, Mushtag M, et al. Myocardial infarction and intramyocardial injection models in swine. Nat Protoc 2012;7:1479-96.CrossRef
22.
Zurück zum Zitat Wang J, Wang Y, Yang M, Shao S, Tian Y, Shao X, et al. Mechanical contraction to guide CRT left-ventricular lead placement instead of electrical activation in myocardial infarction with left ventricular dysfunction: An experimental study based on non-invasive gated myocardial Perfusion imaging and invasive electroanatomic mapping. J Nucl Cardiol. 2019. https://doi.org/10.1007/s12350-019-01710-2.CrossRefPubMed Wang J, Wang Y, Yang M, Shao S, Tian Y, Shao X, et al. Mechanical contraction to guide CRT left-ventricular lead placement instead of electrical activation in myocardial infarction with left ventricular dysfunction: An experimental study based on non-invasive gated myocardial Perfusion imaging and invasive electroanatomic mapping. J Nucl Cardiol. 2019. https://​doi.​org/​10.​1007/​s12350-019-01710-2.CrossRefPubMed
23.
Zurück zum Zitat Shao X, Wang J, Tian Y, Fan S, Zhang F, Yang W, et al. Role of gated myocardial glucose metabolic imaging in assessing left ventricular systolic dyssynchrony after myocardial infarction and the influential factors. Sci Rep. 2018;8:11178.CrossRef Shao X, Wang J, Tian Y, Fan S, Zhang F, Yang W, et al. Role of gated myocardial glucose metabolic imaging in assessing left ventricular systolic dyssynchrony after myocardial infarction and the influential factors. Sci Rep. 2018;8:11178.CrossRef
24.
Zurück zum Zitat Higashi T, Tamaki N, Honda T, Torizuka T, Kimura T, Inokuma T, et al. Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study. J Nucl Med 1997;38:1337-44.PubMed Higashi T, Tamaki N, Honda T, Torizuka T, Kimura T, Inokuma T, et al. Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study. J Nucl Med 1997;38:1337-44.PubMed
25.
Zurück zum Zitat Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med 2001;42:1551-5.PubMed Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med 2001;42:1551-5.PubMed
26.
Zurück zum Zitat Lautamäki R, Schuleri KH, Sasano T, Javadi MS, Youssef A, Merrill J, et al. Integration of infarct size, tissue perfusion, and metabolism by hybrid cardiac positron emission tomography/computed tomography: Evaluation in a porcine model of myocardial infarction. Circ Cardiovasc Imaging 2009;2:299-305.CrossRef Lautamäki R, Schuleri KH, Sasano T, Javadi MS, Youssef A, Merrill J, et al. Integration of infarct size, tissue perfusion, and metabolism by hybrid cardiac positron emission tomography/computed tomography: Evaluation in a porcine model of myocardial infarction. Circ Cardiovasc Imaging 2009;2:299-305.CrossRef
27.
Zurück zum Zitat Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice. Eur J Nucl Med Mol Imaging 2015;42:771-80.CrossRef Thackeray JT, Bankstahl JP, Wang Y, Wollert KC, Bengel FM. Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice. Eur J Nucl Med Mol Imaging 2015;42:771-80.CrossRef
28.
Zurück zum Zitat Cheng VY, Slomka PJ, Ahlen M, Thomson LE, Waxman AD, Berman DS. Impact of carbohydrate restriction with and without fatty acid loading on myocardial 18F-FDG uptake during PET: A randomized controlled trial. J Nucl Cardiol 2010;17:286-91.CrossRef Cheng VY, Slomka PJ, Ahlen M, Thomson LE, Waxman AD, Berman DS. Impact of carbohydrate restriction with and without fatty acid loading on myocardial 18F-FDG uptake during PET: A randomized controlled trial. J Nucl Cardiol 2010;17:286-91.CrossRef
29.
Zurück zum Zitat Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med 2009;50:563-8.CrossRef Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, et al. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med 2009;50:563-8.CrossRef
30.
Zurück zum Zitat Schatka I, Bengel FM. Advanced imaging of cardiac sarcoidosis. J Nucl Med 2014;55:99-106.CrossRef Schatka I, Bengel FM. Advanced imaging of cardiac sarcoidosis. J Nucl Med 2014;55:99-106.CrossRef
31.
Zurück zum Zitat Minamimoto R, Morooka M, Kubota K, Ito K, Masuda-Miyata Y, Mitsumoto T, et al. Value of FDG-PET/CT using unfractionated heparin for managing primary cardiac lymphoma and several key findings. J Nucl Cardiol 2011;18:516-20.CrossRef Minamimoto R, Morooka M, Kubota K, Ito K, Masuda-Miyata Y, Mitsumoto T, et al. Value of FDG-PET/CT using unfractionated heparin for managing primary cardiac lymphoma and several key findings. J Nucl Cardiol 2011;18:516-20.CrossRef
32.
Zurück zum Zitat Toyama H, Ichise M, Liow JS, Vines DC, Seneca NM, Modell KJ, et al. Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol 2004;31:251-6.CrossRef Toyama H, Ichise M, Liow JS, Vines DC, Seneca NM, Modell KJ, et al. Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET. Nucl Med Biol 2004;31:251-6.CrossRef
33.
Zurück zum Zitat Koudstaal S, Gho JM, van Hout GP, Jansen MS, Gründeman PF, et al. Myocardial infarction and functional outcome assessment in pigs. J Vis Exp. 2014;86:e51269. Koudstaal S, Gho JM, van Hout GP, Jansen MS, Gründeman PF, et al. Myocardial infarction and functional outcome assessment in pigs. J Vis Exp. 2014;86:e51269.
Metadaten
Titel
Functional significance of post-myocardial infarction inflammation evaluated by 18F-fluorodeoxyglucose imaging in swine model
verfasst von
Xiao-Ying Xi, MD
Feifei Zhang, MD
Jianfeng Wang, MD
Wei Gao, MD
Yi Tian, MD
Hongyu Xu, MD
Min Xu, MD
Yuetao Wang, MD
Min-Fu Yang, MD
Publikationsdatum
18.11.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Nuclear Cardiology / Ausgabe 2/2020
Print ISSN: 1071-3581
Elektronische ISSN: 1532-6551
DOI
https://doi.org/10.1007/s12350-019-01952-0

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