title: Oxidative myocardial damage in human cocaine-related cardiomyopathy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 0-3), 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.
  
  
  CONCLUSIONS
  Oxidative stress is a major mechanism of myocardial damage in human CCM. It concurs with calcium overload to myocyte dysfunction and death.
authors: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, University 'La Sapienza', Viale del Policlinico 155, I-00161, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
authors: Andrea
authors: A
authors: Frustaci
authors: Matteo A
authors: MA
authors: Russo
authors: Emanuela
authors: E
authors: Morgante
authors: Fernanda
authors: F
authors: Scopelliti
authors: Katia
authors: K
authors: Aquilano
authors: Maria R
authors: MR
authors: Ciriolo
authors: Claudia
authors: C
authors: Grande
authors: Romina
authors: R
authors: Verardo
authors: Cristina
authors: C
authors: Chimenti
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology*; D002374:Catalase / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006335:Heart Injuries / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012189:Retrospective Studies; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D003849:Deoxyguanosine
keywords: Cardiomyopathy; Cocaine; Nitric oxide