{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:49:32Z","timestamp":1788353372419,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T00:00:00Z","timestamp":1423612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The pathogenesis of cocaine-related cardiomyopathy (CCM) is still unclear. Oxidative damage from cocaine-generated reactive oxygen species (ROS) overcoming myocardial antioxidant reserve has been hypothesized by experimental studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Ten (2.3%) of 430 consecutive cases with dilated cardiomyopathy (DCM) were attributed to CCM. Endomyocardial biopsies from CCM were retrospectively investigated with histology, electron microscopy, immunohistochemistry (graded 0\u20133), and Western blot analysis for inducible nitric oxide synthase (iNOS) and nitrotyrosine. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), while apoptosis and necrosis were evaluated by in situ ligation with hairpin probes. Myocardial anti-oxidant reserve was evaluated through assessment of superoxide dismutase (SOD1-2) and catalase (CT) activity in two frozen samples from each patient. Results were compared with idiopathic DCM and normal controls. Cardiomyocytes were bigger and myocardial fibrosis was more pronounced in CCM than in the DCM cohort. Contraction band necrosis was always detectable only in CCM with sparse lymphocytic infiltrates in three cases. Both iNOS and nitrotyrosine were significantly more expressed in CCM than in DCM. Immunostaining for 8-OHdG, cardiomyocyte apoptosis, and necrosis were significantly increased in CCM compared with controls and DCM. Myocardial SOD1 and CT activity was significantly decreased compared with DCM and controls, and correlated with cell death and severity of left ventricular dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Oxidative stress is a major mechanism of myocardial damage in human CCM. It concurs with calcium overload to myocyte dysfunction and death.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.231","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T04:49:57Z","timestamp":1423802997000},"page":"283-290","source":"Crossref","is-referenced-by-count":39,"title":["Oxidative Myocardial Damage in Human Cocaine-Related Cardiomyopathy"],"prefix":"10.1093","volume":"17","author":[{"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, University \u2018La Sapienza\u2019 , Viale del Policlinico 155, I\u201300161, Rome ,","place":["Italy"]},{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo A.","family":"Russo","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Laboratory, IRCCS S. Raffaele Pisana , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Morgante","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, University \u2018La Sapienza\u2019 , Viale del Policlinico 155, I\u201300161, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Scopelliti","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, University \u2018La Sapienza\u2019 , Viale del Policlinico 155, I\u201300161, Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Aquilano","sequence":"additional","affiliation":[{"name":"Department of Biology, Tor Vergata University , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R.","family":"Ciriolo","sequence":"additional","affiliation":[{"name":"Department of Biology, Tor Vergata University , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Grande","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Verardo","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, University \u2018La Sapienza\u2019 , Viale del Policlinico 155, I\u201300161, Rome ,","place":["Italy"]},{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,11]]},"reference":[{"key":"2026011921084356800_ejhf231-bib-0001","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ijcard.2005.09.058","article-title":"Severe cardiomyopathy associated to cocaine abuse","volume":"112","author":"Robledo-Carmona","year":"2006","journal-title":"Int J Cardiol"},{"key":"2026011921084356800_ejhf231-bib-0002","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/0002-8703(88)90078-6","article-title":"Cardiovascular effects of cocaine: an autopsy study of 40 patients","volume":"115","author":"Virmani","year":"1988","journal-title":"Am Heart J"},{"key":"2026011921084356800_ejhf231-bib-0003","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0046-8177(87)80338-6","article-title":"Cocaine and the heart","volume":"18","author":"Tazelaar","year":"1987","journal-title":"Hum Pathol"},{"key":"2026011921084356800_ejhf231-bib-0004","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1097\/00005344-200311000-00010","article-title":"Prolonged cardiac dysfunction after withdrawal of chronic cocaine exposure in rats","volume":"42","author":"Moritz","year":"2003","journal-title":"J Cardiovasc Pharmacol"},{"key":"2026011921084356800_ejhf231-bib-0005","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.yjmcc.2006.11.011","article-title":"NADPH oxidase prevents cocaine-induced up regulation of xanthine oxidoreductase and cardiac dysfunction","volume":"42","author":"Isabelle","year":"2007","journal-title":"J Mol Cell Cardiol"},{"key":"2026011921084356800_ejhf231-bib-0006","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.mehy.2004.06.028","article-title":"Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer","volume":"64","author":"Kovacic","year":"2005","journal-title":"Med Hypotheses"},{"key":"2026011921084356800_ejhf231-bib-0007","doi-asserted-by":"crossref","first-page":"C926","DOI":"10.1152\/ajpcell.00254.2001","article-title":"Role of reactive oxygen species and NADPH oxidase in alpha(1)-adrenoceptor signaling in adult rat cardiac myocytes","volume":"282","author":"Xiao","year":"2002","journal-title":"Am J Physiol"},{"issue":"Suppl 1","key":"2026011921084356800_ejhf231-bib-0008","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1002\/jat.793","article-title":"Toxicology update: the cardiotoxicity of the oxidative stress metabolites of catecholamines (aminochromes)","volume":"21","author":"Behonick","year":"2001","journal-title":"J Appl Toxicol"},{"key":"2026011921084356800_ejhf231-bib-0009","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1161\/01.RES.0000093985.76901.AF","article-title":"Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure","volume":"93","author":"Chimenti","year":"2003","journal-title":"Circ Res"},{"key":"2026011921084356800_ejhf231-bib-0010","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/01.RES.87.12.1123","article-title":"Myocardial cell death in human diabetes","volume":"87","author":"Frustaci","year":"2000","journal-title":"Circ Res"},{"key":"2026011921084356800_ejhf231-bib-0011","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1016\/j.biocel.2008.05.013","article-title":"Glutathione and copper, zinc superoxide dismutase are modulated by overexpression of neuronal nitric oxide synthase","volume":"40","author":"Baldelli","year":"2008","journal-title":"Int J Biochem Cell Biol"},{"key":"2026011921084356800_ejhf231-bib-0012","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/00005792-199907000-00005","article-title":"The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1278 patients","volume":"78","author":"Felker","year":"1999","journal-title":"Medicine"},{"key":"2026011921084356800_ejhf231-bib-0013","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/mus.20907","article-title":"Possible role for nitric oxide dysregulation in critical illness myopathy","volume":"3","author":"Capasso","year":"2008","journal-title":"Muscle & Nerve"},{"issue":"Suppl 1","key":"2026011921084356800_ejhf231-bib-0014","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1002\/jat.793","article-title":"Toxicology update: the cardiotoxicity of the oxidative stress metabolites of catecholamines (aminochromes)","volume":"21","author":"Behonick","year":"2001","journal-title":"J Appl Toxicol"},{"key":"2026011921084356800_ejhf231-bib-0015","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1089\/ars.2012.4615","article-title":"p53 orchestrates the PGC-1\u03b1-mediated antioxidant response upon mild redox and metabolic imbalance","volume":"18","author":"Aquilano","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"2026011921084356800_ejhf231-bib-0016","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/ijc.21904","article-title":"Tumor suppressive activity of a variant isoform of manganese superoxide dismutase released by a human liposarcoma cell line","volume":"119","author":"Mancini","year":"2006","journal-title":"Int J Cancer"},{"key":"2026011921084356800_ejhf231-bib-0017","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1002\/ijc.23791","article-title":"Biophysical and biochemical characterization of a liposarcoma derived recombinant MnSOD protein acting as anticancer agent","volume":"123","author":"Mancini","year":"2008","journal-title":"Int J Cancer"},{"key":"2026011921084356800_ejhf231-bib-0018","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.freeradbiomed.2008.10.030","article-title":"A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells","volume":"46","author":"Borrelli","year":"2009","journal-title":"Free Radic Biol Med"},{"key":"2026011921084356800_ejhf231-bib-0019","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jhep.2012.09.010","article-title":"Recombinant human manganese superoxide dismutase reduces liver fibrosis and portal pressure in CCI4-cirrhotic rats","volume":"58","author":"Guilaume","year":"2013","journal-title":"J Hepatol"},{"key":"2026011921084356800_ejhf231-bib-0020","first-page":"424","article-title":"Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury","volume":"18","author":"Pisani","year":"2014","journal-title":"Clin Exp Nephrol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.231","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/3\/283\/66423578\/eurjhf_17_3_283.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/3\/283\/66423578\/eurjhf_17_3_283.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:08:58Z","timestamp":1768874938000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/17\/3\/283\/8426609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,11]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,2,11]]},"published-print":{"date-parts":[[2015,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.231","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,3]]},"published":{"date-parts":[[2015,2,11]]}}}