Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
EJNMMI Research
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction

Authors: Mélanie Bousquenaud, Fatiha Maskali, Sylvain Poussier, Jennifer Zangrando, Pierre-Yves Marie, Henri Boutley, Renaud Fay, Gilles Karcher, Daniel R Wagner, Yvan Devaux

Published in: EJNMMI Research | Issue 1/2013

Login to get access

Abstract

Background

Adenosine may have beneficial effects on left ventricular function after myocardial infarction (MI), but the magnitude of this effect on remote and MI areas is controversial. We assessed the long-term effects of adenosine after MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission tomography.

Methods

Wistar rats were subjected to coronary ligation and randomized into three groups treated daily for 2 months by NaCl (control; n = 7), 2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an antagonist of adenosine receptors (8-SPT; n = 8).

Results

After 2 months, control rats exhibited left ventricular remodelling, with increased end-diastolic volume and decreased ejection fraction. Left ventricular remodelling was not significantly inhibited by CADO. Segmental contractility, as assessed by the change in myocardial thickening after 2 months, was improved in CADO rats compared to control rats (+1.6% ± 0.8% vs. −2.3% ± 0.8%, p < 0.001). This improvement was significant in border (+5.6% ± 0.8% vs. +1.5% ± 0.8%, p < 0.001) and remote (−4.0% ± 1.0% vs. −10.4% ± 1.3%, p < 0.001) segments, but absent in MI segments. Histological analyses revealed that CADO reduced fibrosis, cardiomyocyte hypertrophy and apoptosis. Protective effects of CADO were blunted by 8-SPT.

Conclusion

Long-term administration of adenosine protects the left ventricle from contractile dysfunction following MI.
Appendix
Available only for authorised users
Literature
1.
Wolk MJ, Scheidt S, Killip T: Heart failure complicating acute myocardial infarction. Circulation 1972, 45: 1125–1138. 10.1161/01.CIR.45.5.1125CrossRef
2.
Jessup M, Brozena S: Heart failure. N Engl J Med 2003, 348: 2007–2018. 10.1056/NEJMra021498CrossRef
3.
Cohn JN, Ferrari R, Sharpe N: Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling: behalf of an international forum on cardiac remodeling. J Am Coll Cardiol 2000, 35: 569–582. 10.1016/S0735-1097(99)00630-0CrossRef
4.
Headrick JP, Peart JN, Reichelt ME, Haseler LJ: Adenosine and its receptors in the heart: regulation, retaliation and adaptation. Biochimica et Biophysica Acta (BBA) - Biomembranes 2011, 1808: 1413–1428. 10.1016/j.bbamem.2010.11.016CrossRef
5.
Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, Stone GW: Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial. Eur Heart J 2006, 27: 2400–2405. 10.1093/eurheartj/ehl094CrossRef
6.
Desmet W, Bogaert J, Dubois C, Sinnaeve P, Adriaenssens T, Pappas C, Ganame J, Dymarkowski S, Janssens S, Belmans A, Van de Werf F: High-dose intracoronary adenosine for myocardial salvage in patients with acute ST-segment elevation myocardial infarction. Eur Heart J 2011, 32: 867–877. 10.1093/eurheartj/ehq492CrossRef
7.
Fokkema ML, Vlaar PJ, Vogelzang M, Gu YL, Kampinga MA, de Smet BJ, Jessurun GA, Anthonio RL, van den Heuvel AF, Tan ES, Zijlstra F: Effect of high-dose intracoronary adenosine administration during primary percutaneous coronary intervention in acute myocardial infarction: a randomized controlled trial. Circ Cardiovasc Interv 2009, 2: 323–329.CrossRef
8.
Wakeno M, Minamino T, Seguchi O, Okazaki H, Tsukamoto O, Okada K, Hirata A, Fujita M, Asanuma H, Kim J, Komamura K, Takashima S, Mochizuki N, Kitakaze M: Long-term stimulation of adenosine A2b receptors begun after myocardial infarction prevents cardiac remodeling in rats. Circulation 2006, 114: 1923–1932. 10.1161/CIRCULATIONAHA.106.630087CrossRef
9.
Wheeler DG, Joseph ME, Mahamud SD, Aurand WL, Mohler PJ, Pompili VJ, Dwyer KM, Nottle MB, Harrison SJ, d'Apice AJ, Robson SC, Cowan PJ, Gumina RJ: Transgenic swine: expression of human CD39 protects against myocardial injury. J Mol Cell Cardiol 2012, 52: 958–961. 10.1016/j.yjmcc.2012.01.002PubMedCentralCrossRef
10.
Bousquenaud M, Maskali F, Poussier S, Marie PY, Boutley H, Karcher G, Wagner DR, Devaux Y: Acipimox-enhanced (18)F-fluorodeoxyglucose positron emission tomography for characterizing and predicting early remodeling in the rat infarct model. Int J Cardiovasc Imaging 2012, 28: 1407–1415. 10.1007/s10554-011-9983-2CrossRef
11.
Maskali F, Poussier S, Marie PY, Tran N, Antunes L, Olivier P, Plenat F, Maitrejean S, Zannad F, Karcher G: High-resolution simultaneous imaging of SPECT, PET, and MRI tracers on histologic sections of myocardial infarction. J Nucl Cardiol 2005, 12: 229–230. 10.1016/j.nuclcard.2004.12.296CrossRef
12.
Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E: Myocardial infarct size and ventricular function in rats. Circ Res 1979, 44: 503–512. 10.1161/01.RES.44.4.503CrossRef
13.
Poussier S, Maskali F, Tran N, Person C, Maureira P, Boutley H, Karcher G, Lacolley P, Regnault V, Fay R, Marie PY: ECG-triggered (18)F-fluorodeoxyglucose positron emission tomography imaging of the rat heart is dramatically enhanced by acipimox. Eur J Nucl Med Mol Imaging 2010, 37: 1745–1750. 10.1007/s00259-010-1418-0CrossRef
14.
Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS: Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002, 105: 539–542. 10.1161/hc0402.102975CrossRef
15.
Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, Van Train KF, Berman DS: Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995, 36: 2138–2147.
16.
Germano G, Kavanagh PB, Berman DS: An automatic approach to the analysis, quantitation and review of perfusion and function from myocardial perfusion SPECT images. Int J Card Imaging 1997, 13: 337–346. 10.1023/A:1005815206195CrossRef
17.
Marie PY, Djaballah W, Franken PR, Vanhove C, Muller MA, Boutley H, Poussier S, Olivier P, Karcher G, Bertrand A: OSEM reconstruction, associated with temporal fourier and depth-dependant resolution recovery filtering, enhances results from sestamibi and 201Tl 16-interval gated SPECT. J Nucl Med 2005, 46: 1789–1795.
18.
Slart RH, Bax JJ, van Veldhuisen DJ, van der Wall EE, Dierckx RA, de Boer J, Jager PL: Prediction of functional recovery after revascularization in patients with coronary artery disease and left ventricular dysfunction by gated FDG-PET. J Nucl Cardiol 2006, 13: 210–219.CrossRef
19.
Soeki T, Kishimoto I, Okumura H, Tokudome T, Horio T, Mori K, Kangawa K: C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction. J Am Coll Cardiol 2005, 45: 608–616. 10.1016/j.jacc.2004.10.067CrossRef
20.
Wang X, Jameel MN, Li Q, Mansoor A, Qiang X, Swingen C, Panetta C, Zhang J: Stem cells for myocardial repair with use of a transarterial catheter. Circulation 2009, 120: S238–246. 10.1161/CIRCULATIONAHA.109.885236PubMedCentralCrossRef
21.
Tao Z, Chen B, Tan X, Zhao Y, Wang L, Zhu T, Cao K, Yang Z, Kan YW, Su H: Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A 2011, 108: 2064–2069. 10.1073/pnas.1018925108PubMedCentralCrossRef
22.
Tran N, Franken PR, Maskali F, Nloga J, Maureira P, Poussier S, Groubatch F, Vanhove C, Villemot JP, Marie PY: Intramyocardial implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT. J Nucl Med 2007, 48: 405–412.
23.
Ernens I, Rouy D, Velot E, Devaux Y, Wagner DR: Adenosine inhibits matrix metalloproteinase-9 secretion by neutrophils: implication of A2A receptor and cAMP/PKA/Ca2+ pathway. Circ Res 2006, 99: 590–597. 10.1161/01.RES.0000241428.82502.d4CrossRef
24.
Velot E, Haas B, Leonard F, Ernens I, Rolland-Turner M, Schwartz C, Longrois D, Devaux Y, Wagner DR: Activation of the adenosine-A3 receptor stimulates matrix metalloproteinase-9 secretion by macrophages. Cardiovasc Res 2008, 80: 246–254. 10.1093/cvr/cvn201CrossRef
25.
Leonard F, Devaux Y, Vausort M, Ernens I, Rolland-Turner M, Wagner DR: Adenosine modifies the balance between membrane and soluble forms of Flt-1. J Leukoc Biol 2011, 90: 199–204. 10.1189/jlb.0910505CrossRef
26.
Rolland-Turner M, Goretti E, Bousquenaud M, Leonard F, Nicolas C, Zhang L, Maskali F, Marie PY, Devaux Y, Wagner D: Adenosine stimulates the migration of human endothelial progenitor cells: role of CXCR4 and microRNA-150. PLoS ONE 2013, 8: e54135. 10.1371/journal.pone.0054135PubMedCentralCrossRef
27.
Simonis G, Wiedemann S, Joachim D, Weinbrenner C, Marquetant R, Strasser RH: Stimulation of adenosine A2b receptors blocks apoptosis in the non-infarcted myocardium even when administered after the onset of infarction. Mol Cell Biochem 2009, 328: 119–126. 10.1007/s11010-009-0081-xCrossRef
28.
Fassett JT, Hu X, Xu X, Lu Z, Zhang P, Chen Y, Bache RJ: Adenosine kinase regulation of cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 2011, 300: H1722-H1732. 10.1152/ajpheart.00684.2010PubMedCentralCrossRef
29.
Ali SM, Brown EJ Jr, Nallapati SR, Alhaddad IA: Early angiotensin converting enzyme inhibitor therapy after experimental myocardial infarction prevents left ventricular dilation by reducing infarct expansion: a possible mechanism of clinical benefits. Coron Artery Dis 1998, 9: 815–821. 10.1097/00019501-199809120-00006CrossRef
30.
Steinberg SF, Zhang H, Pak E, Pagnotta G, Boyden PA: Characteristics of the beta-adrenergic receptor complex in the epicardial border zone of the 5-day infarcted canine heart. Circulation 1995, 91: 2824–2833. 10.1161/01.CIR.91.11.2824CrossRef
31.
Ryzhov S, Zhang Q, Biaggioni I, Feoktistov I: Adenosine A2B receptors on cardiac stem cell antigen (Sca)-1-positive stromal cells play a protective role in myocardial infarction. Am J Pathol 2013, 183: 665–672. 10.1016/j.ajpath.2013.05.012PubMedCentralCrossRef
32.
Toldo S, Zhong H, Mezzaroma E, Van Tassell B, Kannan H, Zeng D, Belardinelli L, Voelkel N, Abbate A: GS-6201, a selective blocker of the A2B adenosine receptor, attenuates cardiac remodeling following acute myocardial infarction in the mouse. J Pharmacol Exp Ther 2012, 343: 587–595. 10.1124/jpet.111.191288CrossRef
33.
Eltzschig HK, Bonney SK, Eckle T: Attenuating myocardial ischemia by targeting A2B adenosine receptors. Trends Mol Med 2013, 19: 345–354. 10.1016/j.molmed.2013.02.005PubMedCentralCrossRef
34.
Matherne GP, Linden J, Byford AM, Gauthier NS, Headrick JP: Transgenic A1 adenosine receptor overexpression increases myocardial resistance to ischemia. Proc Natl Acad Sci U S A 1997, 94: 6541–6546. 10.1073/pnas.94.12.6541PubMedCentralCrossRef
35.
Albrecht-Kupper BE, Leineweber K, Nell PG: Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal 2012, 8: 91–99.PubMedCentralCrossRef
36.
Lu Z, Fassett J, Xu X, Hu X, Zhu G, French J, Zhang P, Schnermann J, Bache RJ, Chen Y: Adenosine A3 receptor deficiency exerts unanticipated protective effects on the pressure-overloaded left ventricle. Circulation 2008, 118: 1713–1721. 10.1161/CIRCULATIONAHA.108.788307PubMedCentralCrossRef
37.
Du L, Gao ZG, Nithipatikom K, Ijzerman AP, Veldhoven JP, Jacobson KA, Gross GJ, Auchampach JA: Protection from myocardial ischemia/reperfusion injury by a positive allosteric modulator of the A(3) adenosine receptor. J Pharmacol Exp Ther 2012, 340: 210–217. 10.1124/jpet.111.187559PubMedCentralCrossRef
Metadata
Title
Cardioprotective effects of adenosine within the border and remote areas of myocardial infarction
Authors
Mélanie Bousquenaud
Fatiha Maskali
Sylvain Poussier
Jennifer Zangrando
Pierre-Yves Marie
Henri Boutley
Renaud Fay
Gilles Karcher
Daniel R Wagner
Yvan Devaux
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-65

Other articles of this Issue 1/2013

EJNMMI Research 1/2013 Go to the issue

Original research

Noninvasive k3 estimation method for slow dissociation PET ligands: application to [11C]Pittsburgh compound B

Original research

11C-LY2428703, a positron emission tomographic radioligand for the metabotropic glutamate receptor 1, is unsuitable for imaging in monkey and human brains

Original research

Comparison between kinetic modelling and graphical analysis for the quantification of [18F]fluoromethylcholine uptake in mice

Letter to the Editor

About inflammation and infection

Original research

Radiosynthesis and preclinical evaluation of [11C]prucalopride as a potential agonist PET ligand for the 5-HT4 receptor

Original research

Pulmonary vein isolation in patients with paroxysmal atrial fibrillation is associated with regional cardiac sympathetic denervation