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.
Eur J Heart Fail. 2015 Mar;17(3):283-90. doi: 10.1002/ejhf.231. Epub 2015 Feb 11.
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.
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.
Oxidative stress is a major mechanism of myocardial damage in human CCM. It concurs with calcium overload to myocyte dysfunction and death.
可卡因相关性心肌病（CCM）的发病机制仍不清楚。实验研究假设，可卡因产生的活性氧（ROS）引起的氧化损伤超过了心肌抗氧化储备。
在 430 例连续扩张型心肌病（DCM）患者中，有 10 例（2.3%）归因于 CCM。回顾性研究了 CCM 的心肌活检标本，进行组织学、电镜、免疫组织化学（0-3 级）检查，并通过 Western blot 分析诱导型一氧化氮合酶（iNOS）和硝基酪氨酸。通过免疫染色检测 8-羟基脱氧鸟苷（8-OHdG）评估 DNA 的氧化损伤，通过发夹探针原位连接评估细胞凋亡和坏死。通过评估每个患者两个冷冻样本中的超氧化物歧化酶（SOD1-2）和过氧化氢酶（CT）活性来评估心肌抗氧化储备。结果与特发性 DCM 和正常对照组进行比较。与 DCM 组相比，CCM 中的心肌细胞更大，心肌纤维化更明显。在三个病例中，仅在 CCM 中检测到收缩带坏死，且淋巴细胞浸润稀疏。与 DCM 相比，CCM 中 iNOS 和硝基酪氨酸的表达明显更高。与对照组和 DCM 相比，CCM 中 8-OHdG 免疫染色、心肌细胞凋亡和坏死明显增加。与 DCM 和对照组相比，心肌 SOD1 和 CT 活性明显降低，与细胞死亡和左心室功能障碍的严重程度相关。
氧化应激是人类 CCM 心肌损伤的主要机制。它与肌细胞功能障碍和死亡的钙超载一致。
