Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies

Journal of Molecular and Cellular Cardiology - Tập 52 Số 6 - Trang 1213-1225 - 2012
Yanti Octavia1, Carlo G. Tocchetti2, Kathleen L. Gabrielson3, Stefan Janssens4, Harry J.G.M. Crijns1, An L. Moens1
1Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Dept. of Cardiology, Maastricht, The Netherlands
2Div. of Cardiology, National Cancer Institute, Pascale Foundation, Naples, Italy
3Johns Hopkins Medical Institutions, Dept. of Molecular and Comparative Pathobiology, Baltimore, USA
4Department of Cardiology, Gasthuisberg University Hospital, University of Leuven, Leuven, Belgium

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Tài liệu tham khảo

Allen, 1992, The cardiotoxicity of chemotherapeutic drugs, Semin Oncol, 19, 529

Jain, 2000, Cardiotoxicity of doxorubicin and other anthracycline derivatives, J Nucl Cardiol, 7, 53, 10.1067/mnc.2000.103324

Lipshultz, 1995, Female sex and drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer, N Engl J Med, 332, 1738, 10.1056/NEJM199506293322602

Lanzarini, 2000, Lack of clinically significant cardiac dysfunction during intermediate dobutamine doses in long-term childhood cancer survivors exposed to anthracyclines, Am Heart J, 140, 315, 10.1067/mhj.2000.108237

Sorensen, 1995, Cardiac function in Wilms' tumor survivors, J Clin Oncol, 13, 1546, 10.1200/JCO.1995.13.7.1546

Silber, 1993, Increased risk of cardiac dysfunction after anthracyclines in girls, Med Pediatr Oncol, 21, 477, 10.1002/mpo.2950210704

Biancaniello, 1980, Doxorubicin cardiotoxicity in children, J Pediatr, 97, 45, 10.1016/S0022-3476(80)80128-4

Hershman, 2008, Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma, J Clin Oncol, 26, 3159, 10.1200/JCO.2007.14.1242

Godoy, 1997, Anthracycline-induced cardiotoxicity in children with malignancies, Acta Paediatr Jpn, 39, 188, 10.1111/j.1442-200X.1997.tb03579.x

Pein, 2004, Cardiac abnormalities 15years and more after adriamycin therapy in 229 childhood survivors of a solid tumour at the Institut Gustave Roussy, Br J Cancer, 91, 37, 10.1038/sj.bjc.6601904

Saltiel, 1983, Doxorubicin (adriamycin) cardiomyopathy, West J Med, 139, 332

Singal, 1998, Doxorubicin-induced cardiomyopathy, N Engl J Med, 339, 900, 10.1056/NEJM199809243391307

Kremer, 2002, Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review, Ann Oncol, 13, 503, 10.1093/annonc/mdf118

Xu, 2001, Effects by doxorubicin on the myocardium are mediated by oxygen free radicals, Life Sci, 68, 889, 10.1016/S0024-3205(00)00990-5

Simunek, 2009, Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron, Pharmacol Rep, 61, 154, 10.1016/S1734-1140(09)70018-0

Horenstein, 2000, Molecular basis of anthracycline-induced cardiotoxicity and its prevention, Mol Genet Metab, 71, 436, 10.1006/mgme.2000.3043

Doroshow, 1980, Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin, J Clin Invest, 65, 128, 10.1172/JCI109642

Goormaghtigh, 1980, Evidence of a complex between adriamycin derivatives and cardiolipin: possible role in cardiotoxicity, Biochem Pharmacol, 29, 3003, 10.1016/0006-2952(80)90050-7

Schlame, 2000, The biosynthesis and functional role of cardiolipin, Prog Lipid Res, 39, 257, 10.1016/S0163-7827(00)00005-9

Kashfi, 1990, Inhibition of mitochondrial carnitine palmitoyltransferases by adriamycin and adriamycin analogues, Biochem Pharmacol, 40, 1441, 10.1016/0006-2952(90)90438-Q

Ventura-Clapier, 2004, Energy metabolism in heart failure, J Physiol, 555, 1, 10.1113/jphysiol.2003.055095

Cole, 2006, The protective roles of nitric oxide and superoxide dismutase in adriamycin-induced cardiotoxicity, Cardiovasc Res, 69, 186, 10.1016/j.cardiores.2005.07.012

Minotti, 2004, Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity, Pharmacol Rev, 56, 185, 10.1124/pr.56.2.6

Papadopoulou, 1999, Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression, Biochem Pharmacol, 57, 481, 10.1016/S0006-2952(98)00305-0

Carvalho, 2010, Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy, Toxicology, 270, 92, 10.1016/j.tox.2010.01.019

Suliman, 2007, The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy, J Clin Invest, 117, 3730

Piantadosi, 2008, Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1, Circ Res, 103, 1232, 10.1161/01.RES.0000338597.71702.ad

Pani, 2000, Deregulated manganese superoxide dismutase expression and resistance to oxidative injury in p53-deficient cells, Cancer Res, 60, 4654

Kim, 2006, Protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity, Eur J Pharmacol, 541, 24, 10.1016/j.ejphar.2006.04.045

Xiong, 2006, Attenuation of doxorubicin-induced contractile and mitochondrial dysfunction in mouse heart by cellular glutathione peroxidase, Free Radic Biol Med, 41, 46, 10.1016/j.freeradbiomed.2006.02.024

Vasquez-Vivar, 1997, Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin, Biochemistry, 36, 11293, 10.1021/bi971475e

Kalivendi, 2001, Doxorubicin-induced apoptosis is associated with increased transcription of endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and calcium, J Biol Chem, 276, 47266, 10.1074/jbc.M106829200

Moens, 2009, Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor, J Mol Cell Cardiol, 47, 576, 10.1016/j.yjmcc.2009.06.005

Neilan, 2007, Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin, Circulation, 116, 506, 10.1161/CIRCULATIONAHA.106.652339

Duquaine, 2003, Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase, Vasc Med, 8, 101, 10.1191/1358863x03vm476oa

Mukhopadhyay, 2009, Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro, Am J Physiol Heart Circ Physiol, 296, H1466, 10.1152/ajpheart.00795.2008

Fu, 2004, Human neuronal nitric oxide synthase can catalyze one-electron reduction of adriamycin: role of flavin domain, Arch Biochem Biophys, 427, 180, 10.1016/j.abb.2004.04.030

Liu, 2006, Nitric oxide synthase expressions in ADR-induced cardiomyopathy in rats, J Biochem Mol Biol, 39, 759, 10.5483/BMBRep.2006.39.6.759

Deng, 2007, Gp91phox-containing NAD(P)H oxidase increases superoxide formation by doxorubicin and NADPH, Free Radic Biol Med, 42, 466, 10.1016/j.freeradbiomed.2006.11.013

Gilleron, 2009, NADPH oxidases participate to doxorubicin-induced cardiac myocyte apoptosis, Biochem Biophys Res Commun, 388, 727, 10.1016/j.bbrc.2009.08.085

Wojnowski, 2005, NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity, Circulation, 112, 3754, 10.1161/CIRCULATIONAHA.105.576850

Blanco, 2008, Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer, Cancer, 112, 2789, 10.1002/cncr.23534

May, 1980, Solution chemistry studies of adriamycin–iron complexes present in vivo, Eur J Cancer, 16, 1275, 10.1016/0014-2964(80)90189-9

Kappus, 1980, In vivo studies on adriamycin-induced lipid peroxidation and effects of ferrous ions, Dev Toxicol Environ Sci, 8, 635

Xu, 2005, Molecular pharmacology of the interaction of anthracyclines with iron, Mol Pharmacol, 68, 261, 10.1124/mol.105.013383

Minotti, 1998, The secondary alcohol metabolite of doxorubicin irreversibly inactivates aconitase/iron regulatory protein-1 in cytosolic fractions from human myocardium, FASEB J, 12, 541, 10.1096/fasebj.12.7.541

Miranda, 2003, Hfe deficiency increases susceptibility to cardiotoxicity and exacerbates changes in iron metabolism induced by doxorubicin, Blood, 102, 2574, 10.1182/blood-2003-03-0869

Panjrath, 2007, Potentiation of doxorubicin cardiotoxicity by iron loading in a rodent model, J Am Coll Cardiol, 49, 2457, 10.1016/j.jacc.2007.02.060

Barton, 2000, Transfusion iron overload in adults with acute leukemia: manifestations and therapy, Am J Med Sci, 319, 73, 10.1097/00000441-200002000-00001

Dhalla, 2000, Role of oxidative stress in cardiovascular diseases, J Hypertens, 18, 655, 10.1097/00004872-200018060-00002

Bjelogrlic, 2005, Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice, Basic Clin Pharmacol Toxicol, 97, 311, 10.1111/j.1742-7843.2005.pto_166.x

Nitobe, 2003, Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes, Cardiovasc Res, 57, 119, 10.1016/S0008-6363(02)00646-6

Liu, 2007, Effect of curcumin on expression of survivin, Bcl-2 and Bax in human multiple myeloma cell line, Zhongguo Shi Yan Xue Ye Xue Za Zhi, 15, 762

Vedam, 2010, Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice, Am J Physiol Heart Circ Physiol, 298, H1832, 10.1152/ajpheart.01047.2009

Shan, 2003, Hsp10 and Hsp60 modulate Bcl-2 family and mitochondria apoptosis signaling induced by doxorubicin in cardiac muscle cells, J Mol Cell Cardiol, 35, 1135, 10.1016/S0022-2828(03)00229-3

Fan, 2008, Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity, Circ Res, 103, 1270, 10.1161/CIRCRESAHA.108.182832

Kim, 2009, Extracellular heat shock protein 60, cardiac myocytes, and apoptosis, Circ Res, 105, 1186, 10.1161/CIRCRESAHA.109.209643

Rayner, 2008, Extracellular release of the atheroprotective heat shock protein 27 is mediated by estrogen and competitively inhibits acLDL binding to scavenger receptor-A, Circ Res, 103, 133, 10.1161/CIRCRESAHA.108.172155

Nozaki, 2004, Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2-knockout mice, Circulation, 110, 2869, 10.1161/01.CIR.0000146889.46519.27

Riad, 2008, Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice, Eur J Heart Fail, 10, 233, 10.1016/j.ejheart.2008.01.004

Chen, 2007, Effects of oxymatrine on expression of nuclear factor kappa B in kidneys of rats with adriamycin-induced chronic renal fibrosis, Nan Fang Yi Ke Da Xue Xue Bao, 27, 345

Wang, 2002, Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide, Biochem J, 367, 729, 10.1042/bj20020752

Ueno, 2006, Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo, J Pharmacol Sci, 101, 151, 10.1254/jphs.FP0050980

Youn, 2005, Induction of caspase-independent apoptosis in H9c2 cardiomyocytes by adriamycin treatment, Mol Cell Biochem, 270, 13, 10.1007/s11010-005-2541-2

Bruynzeel, 2007, Caspase-dependent and -independent suppression of apoptosis by monoHER in doxorubicin treated cells, Br J Cancer, 96, 450, 10.1038/sj.bjc.6603598

Maejima, 2005, Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation, J Mol Cell Cardiol, 38, 163, 10.1016/j.yjmcc.2004.10.012

d'Anglemont de Tassigny, 2008, The volume-sensitive chloride channel inhibitors prevent both contractile dysfunction and apoptosis induced by doxorubicin through PI3kinase, Akt and Erk 1/2, Eur J Heart Fail, 10, 39, 10.1016/j.ejheart.2007.11.002

Kalivendi, 2005, Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium, Biochem J, 389, 527, 10.1042/BJ20050285

Arai, 2000, Mechanism of doxorubicin-induced inhibition of sarcoplasmic reticulum Ca(2+)-ATPase gene transcription, Circ Res, 86, 8, 10.1161/01.RES.86.1.8

Holmberg, 1990, Patterns of interaction between anthraquinone drugs and the calcium-release channel from cardiac sarcoplasmic reticulum, Circ Res, 67, 272, 10.1161/01.RES.67.2.272

Saeki, 2002, Doxorubicin directly binds to the cardiac-type ryanodine receptor, Life Sci, 70, 2377, 10.1016/S0024-3205(02)01524-2

Caroni, 1981, The cardiotoxic antibiotic doxorubicin inhibits the Na+/Ca2+ exchange of dog heart sarcolemmal vesicles, FEBS Lett, 130, 184, 10.1016/0014-5793(81)81115-5

Keung, 1991, L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations, J Clin Invest, 87, 2108, 10.1172/JCI115241

Favero, 1995, Hydrogen peroxide stimulates the Ca2+ release channel from skeletal muscle sarcoplasmic reticulum, J Biol Chem, 270, 25557, 10.1074/jbc.270.43.25557

Nakagawa, 2000, Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta, Nature, 403, 98, 10.1038/47513

Jang, 2004, Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats, FEBS Lett, 577, 483, 10.1016/j.febslet.2004.10.053

Sawyer, 2002, Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity, Circulation, 105, 1551, 10.1161/01.CIR.0000013839.41224.1C

Lim, 2004, Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes, J Biol Chem, 279, 8290, 10.1074/jbc.M308033200

Solem, 1996, Dose-dependent increase in sensitivity to calcium-induced mitochondrial dysfunction and cardiomyocyte cell injury by doxorubicin, J Mol Cell Cardiol, 28, 1023, 10.1006/jmcc.1996.0095

Chacon, 1992, A digitized-fluorescence-imaging study of mitochondrial Ca2+ increase by doxorubicin in cardiac myocytes, Biochem J, 281, 871, 10.1042/bj2810871

Gabrielson, 2007, Heat shock protein 90 and ErbB2 in the cardiac response to doxorubicin injury, Cancer Res, 67, 1436, 10.1158/0008-5472.CAN-06-3721

Peng, 2005, Heat shock protein 90 stabilization of ErbB2 expression is disrupted by ATP depletion in myocytes, J Biol Chem, 280, 13148, 10.1074/jbc.M410838200

Negro, 2006, erbB2 is required for G protein-coupled receptor signaling in the heart, Proc Natl Acad Sci, 103, 15889, 10.1073/pnas.0607499103

Tripathy, 2004, Effect of cardiac dysfunction on treatment outcomes in women receiving trastuzumab for HER2-overexpressing metastatic breast cancer, Clin Breast Cancer, 5, 293, 10.3816/CBC.2004.n.033

Tokarska-Schlattner, 2005, Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply, Am J Physiol Heart Circ Physiol, 289, H37, 10.1152/ajpheart.01057.2004

Keller, 1986, Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity, Magn Reson Med, 3, 834, 10.1002/mrm.1910030603

Nicolay, 1987, Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity, Biochim Biophys Acta, 929, 5, 10.1016/0167-4889(87)90234-5

Bordoni, 1999, The impairment of essential fatty acid metabolism as a key factor in doxorubicin-induced damage in cultured rat cardiomyocytes, Biochim Biophys Acta, 1440, 100, 10.1016/S1388-1981(99)00113-4

Chatham, 1990, The relationship between cardiac function and metabolism in acute adriamycin-treated perfused rat hearts studied by 31P and 13C NMR spectroscopy, J Mol Cell Cardiol, 22, 1187, 10.1016/0022-2828(90)90082-D

Thomas, 1994, Free radical inactivation of rabbit muscle creatinine kinase: catalysis by physiological and hydrolyzed ICRF-187 (ICRF-198) iron chelates, Free Radic Res, 21, 387, 10.3109/10715769409056591

Mihm, 2002, Intracellular distribution of peroxynitrite during doxorubicin cardiomyopathy: evidence for selective impairment of myofibrillar creatine kinase, Br J Pharmacol, 135, 581, 10.1038/sj.bjp.0704495

Suzuki, 2001, A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes, Am J Physiol Regul Integr Comp Physiol, 280, R1399, 10.1152/ajpregu.2001.280.5.R1399

Picard, 1998, Coordinated upregulation of the cardiac endothelin system in a rat model of heart failure, J Cardiovasc Pharmacol, 31, S294, 10.1097/00005344-199800001-00082

Pieske, 1999, Functional effects of endothelin and regulation of endothelin receptors in isolated human nonfailing and failing myocardium, Circulation, 99, 1802, 10.1161/01.CIR.99.14.1802

Sayed-Ahmed, 2001, Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced cardiomyopathy, Pharmacol Toxicol, 89, 140, 10.1034/j.1600-0773.2001.d01-148.x

Luscher, 2000, Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs, Circulation, 102, 2434, 10.1161/01.CIR.102.19.2434

Miller, 1993, Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effects are attenuated by nitroglycerin in vivo, Am J Hypertens, 6, 156, 10.1093/ajh/6.2.156

Bien, 2007, The endothelin receptor blocker bosentan inhibits doxorubicin-induced cardiomyopathy, Cancer Res, 67, 10428, 10.1158/0008-5472.CAN-07-1344

Yang, 2004, Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice, Circulation, 109, 255, 10.1161/01.CIR.0000105701.98663.D4

Spinale, 2007, Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function, Physiol Rev, 87, 1285, 10.1152/physrev.00012.2007

Goetzenich, 2009, Alteration of matrix metalloproteinases in selective left ventricular adriamycin-induced cardiomyopathy in the pig, J Heart Lung Transplant, 28, 1087, 10.1016/j.healun.2009.06.025

Spallarossa, 2006, Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: the role of MAP kinases and NAD(P)H oxidase, Cardiovasc Res, 69, 736, 10.1016/j.cardiores.2005.08.009

Tokarska-Schlattner, 2010, Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes, Am J Physiol Regul Integr Comp Physiol, 298, R1075, 10.1152/ajpregu.00360.2009

Singh, 2010, Diclofenac sodium, a nonselective nonsteroidal anti-inflammatory drug aggravates doxorubicin-induced cardiomyopathy in rats, J Cardiovasc Pharmacol, 55, 139, 10.1097/FJC.0b013e3181c87e17

Dowd, 2001, Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo, J Clin Invest, 108, 585, 10.1172/JCI200111334

Horie, 2010, Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin–ErbB pathway, Cardiovasc Res, 87, 656, 10.1093/cvr/cvq148

Andrieu-Abadie, 1999, l-Carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation, FASEB J, 13, 1501, 10.1096/fasebj.13.12.1501

d'Anglemont de Tassigny, 2004, Volume-sensitive chloride channels (ICl,vol) mediate doxorubicin-induced apoptosis through apoptotic volume decrease in cardiomyocytes, Fundam Clin Pharmacol, 18, 531, 10.1111/j.1472-8206.2004.00273.x

Mukhopadhyay, 2007, Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity, J Am Coll Cardiol, 50, 528, 10.1016/j.jacc.2007.03.057

Mukhopadhyay, 2010, CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes, Cardiovasc Res, 85, 773, 10.1093/cvr/cvp369

Hydock, 2009, Anandamide preserves cardiac function and geometry in an acute doxorubicin cardiotoxicity rat model, J Cardiovasc Pharmacol Ther, 14, 59, 10.1177/1074248408329449

Torti, 1986, Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy, Cancer Res, 46, 3722

Bristow, 1982, Toxic cardiomyopathy due to doxorubicin, Hosp Pract (Off Ed), 17, 101, 10.1080/21548331.1982.11702439

Takemura, 2007, Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management, Prog Cardiovasc Dis, 49, 330, 10.1016/j.pcad.2006.10.002

Hengel, 2006, Subacute anthracycline cardiotoxicity, Heart Lung Circ, 15, 59, 10.1016/j.hlc.2005.06.003

Saini, 1987, Reversibility of severe left ventricular dysfunction due to doxorubicin cardiotoxicity. Report of three cases, Ann Intern Med, 106, 814, 10.7326/0003-4819-106-6-814

Cohen, 1982, Reversible doxorubicin-induced congestive heart failure, Arch Intern Med, 142, 1570, 10.1001/archinte.1982.00340210168032

McKillop, 1983, Sensitivity and specificity of radionuclide ejection fractions in doxorubicin cardiotoxicity, Am Heart J, 106, 1048, 10.1016/0002-8703(83)90651-8

Tjeerdsma, 1999, Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables, Heart, 81, 419, 10.1136/hrt.81.4.419

Panjrath, 2006, Monitoring chemotherapy-induced cardiotoxicity: role of cardiac nuclear imaging, J Nucl Cardiol, 13, 415, 10.1016/j.nuclcard.2006.03.002

Gabrielson, 2008, Detection of dose response in chronic doxorubicin-mediated cell death with cardiac technetium 99m annexin V single-photon emission computed tomography, Mol Imaging, 7, 132, 10.2310/7290.2008.00015

Migrino, 2008, Early detection of doxorubicin cardiomyopathy using two-dimensional strain echocardiography, Ultrasound Med Biol, 34, 208, 10.1016/j.ultrasmedbio.2007.07.018

Klewer, 1992, Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer, J Am Coll Cardiol, 19, 394, 10.1016/0735-1097(92)90497-B

Elbl, 2003, The evaluation of left ventricular function in childhood cancer survivors by pharmacological stress echocardiography, Neoplasma, 50, 191

Marchandise, 1989, Early detection of doxorubicin cardiotoxicity: interest of Doppler echocardiographic analysis of left ventricular filling dynamics, Am Heart J, 118, 92, 10.1016/0002-8703(89)90077-X

Stoddard, 1992, Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans, J Am Coll Cardiol, 20, 62, 10.1016/0735-1097(92)90138-D

Lipshultz, 2004, The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia, N Engl J Med, 351, 145, 10.1056/NEJMoa035153

Hayakawa, 2001, Plasma levels of natriuretic peptides in relation to doxorubicin-induced cardiotoxicity and cardiac function in children with cancer, Med Pediatr Oncol, 37, 4, 10.1002/mpo.1155

Suzuki, 1998, Elevated B-type natriuretic peptide levels after anthracycline administration, Am Heart J, 136, 362, 10.1053/hj.1998.v136.89908

Erttmann, 1988, Pharmacokinetics of doxorubicin in man: dose and schedule dependence, J Cancer Res Clin Oncol, 114, 509, 10.1007/BF00391502

Creech, 1980, An effective low-dose adriamycin regimen as secondary chemotherapy for metastatic breast cancer patients, Cancer, 46, 433, 10.1002/1097-0142(19800801)46:3<433::AID-CNCR2820460302>3.0.CO;2-6

Schroeder, 2005, Metabolism of the one-ring open metabolites of the cardioprotective drug dexrazoxane to its active metal-chelating form in the rat, Drug Metab Dispos, 33, 1367, 10.1124/dmd.105.005546

Hasinoff, 1990, The hydrolysis activation of the doxorubicin cardioprotective agent ICRF-187 [+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane), Drug Metab Dispos, 18, 344

Lebrecht, 2007, Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats, Br J Pharmacol, 151, 771, 10.1038/sj.bjp.0707294

Barry, 2008, Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane, J Clin Oncol, 26, 1106, 10.1200/JCO.2007.12.2481

Tebbi, 2007, Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease, J Clin Oncol, 25, 493, 10.1200/JCO.2005.02.3879

Hensley, 2009, American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants, J Clin Oncol, 27, 127, 10.1200/JCO.2008.17.2627

van Acker, 1993, Cardioprotective properties of O-(beta-hydroxyethyl)-rutosides in doxorubicin-pretreated BALB/c mice, Cancer Res, 53, 4603

van Acker, 2001, New synthetic flavonoids as potent protectors against doxorubicin-induced cardiotoxicity, Free Radic Biol Med, 31, 31, 10.1016/S0891-5849(01)00546-9

van Acker, 1995, Monohydroxyethylrutoside as protector against chronic doxorubicin-induced cardiotoxicity, Br J Pharmacol, 115, 1260, 10.1111/j.1476-5381.1995.tb15034.x

van Acker, 1997, Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin, Clin Cancer Res, 3, 1747

Bruynzeel, 2007, The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study, Br J Cancer, 97, 1084, 10.1038/sj.bjc.6603994

Kalay, 2006, Protective effects of carvedilol against anthracycline-induced cardiomyopathy, J Am Coll Cardiol, 48, 2258, 10.1016/j.jacc.2006.07.052

Georgakopoulos, 2010, Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up, Am J Hematol, 85, 894, 10.1002/ajh.21840

Tallaj, 2005, Response of doxorubicin-induced cardiomyopathy to the current management strategy of heart failure, J Heart Lung Transplant, 24, 2196, 10.1016/j.healun.2004.12.108

Jensen, 1996, Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy, Lancet, 347, 297, 10.1016/S0140-6736(96)90469-9

Sacco, 2001, Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat, Eur J Pharmacol, 414, 71, 10.1016/S0014-2999(01)00782-8

al-Shabanah, 1998, Captopril ameliorates myocardial and hematological toxicities induced by adriamycin, Biochem Mol Biol Int, 45, 419

Sacco, 2009, ACE inhibition and protection from doxorubicin-induced cardiotoxicity in the rat, Vascul Pharmacol, 50, 166, 10.1016/j.vph.2009.01.001

Ibrahim, 2009, Angiotensin-converting enzyme inhibition and angiotensin AT(1)-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity, Pharmacol Res, 60, 373, 10.1016/j.phrs.2009.05.007

Ramond, 2008, Erythropoietin pretreatment protects against acute chemotherapy toxicity in isolated rat hearts, Exp Biol Med (Maywood), 233, 76, 10.3181/0706-RM-152

Engert, 2010, Epoetin alfa in patients with advanced-stage Hodgkin's lymphoma: results of the randomized placebo-controlled GHSG HD15EPO trial, J Clin Oncol, 28, 2239, 10.1200/JCO.2009.25.1835

Fisher, 2005, Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity, Circulation, 111, 1601, 10.1161/01.CIR.0000160359.49478.C2

Di, 2010, Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells, Breast Cancer Res Treat, 124, 349, 10.1007/s10549-010-0765-7

Das, 2010, Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction, Proc Natl Acad Sci U S A, 107, 18202, 10.1073/pnas.1006965107

Gross, 2011, Evidence for pleiotropic effects of phosphodiesterase-5 (PDE5) inhibitors: emerging concepts in cancer and cardiovascular medicine, Circ Res, 108, 1040, 10.1161/RES.0b013e31821d2c31

Tatlidede, 2009, Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage, Free Radic Res, 43, 195, 10.1080/10715760802673008

Ajijola, 2008, Usefulness of cardiac resynchronization therapy in the management of doxorubicin-induced cardiomyopathy, Am J Cardiol, 101, 1371, 10.1016/j.amjcard.2007.12.037

Ward, 2004, Pediatric heart transplantation for anthracycline cardiomyopathy: cancer recurrence is rare, J Heart Lung Transplant, 23, 1040, 10.1016/j.healun.2003.08.014

van Dalen, 2010, Different anthracycline derivates for reducing cardiotoxicity in cancer patients, Cochrane Database Syst Rev, CD005006

Suter, 2007, Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial, J Clin Oncol, 25, 3859, 10.1200/JCO.2006.09.1611

Eschenhagen, 2011, Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology, Eur J Heart Fail, 13, 1, 10.1093/eurjhf/hfq213