Vaillant F, Turrel F, Bost M, Bricca G, Descotes J, Bui-Xuan B, Tabib A, Manati W, Timour Q
Laboratory of Medical Pharmacology (INSERM ERI22), Claude Bernard University, Lyon, France.
J Appl Toxicol. 2008 Mar;28(2):212-6. doi: 10.1002/jat.1279.
Organic and/or functional heart lesions sometimes resulting in sudden death have been described in psychiatric patients treated with neuroleptics. As selenium has been suggested previously to play a role in the development of such lesions, the present study was undertaken to determine whether a correlation could be found between heart lesions induced by neuroleptics and changes in blood selenium as well as myocardial tissue concentrations in the rabbit. Twelve NZW adult rabbits were treated intramuscularly with both levomepromazine (3 mg kg(-1) day(-1)) and risperidone (1 mg kg(-1) once every other week) for 3 months, and compared with 12 saline-treated controls. Blood samples were drawn before and at the end of the study. Tissue samples from the heart, liver and kidneys were obtained at the end of treatment, and the hearts were examined histologically. Heart lesions including disorganization of cardiac fibers, myolysis, interstitial and endocardial fibrosis, and necrosis were noted in treated animals, but not in controls. There was a 20% decrease in selenium blood levels and a 50% decrease in selenium myocardial tissue levels in treated animals compared with controls (P < 0.001). In contrast, no differences in selenium levels in liver and kidneys were found across the experimental groups. These results suggest a possible correlation between selenium depletion and neuroleptics-induced heart lesions.
在接受抗精神病药物治疗的精神病患者中，曾有过关于有时会导致猝死的器质性和/或功能性心脏病变的描述。由于此前有人提出硒在这类病变的发生发展中起作用，因此开展了本研究，以确定在兔子中抗精神病药物诱发的心脏病变与血硒以及心肌组织中硒浓度的变化之间是否存在关联。12只成年新西兰白兔每隔一周肌肉注射一次左美丙嗪（3毫克/千克/天）和利培酮（1毫克/千克），持续3个月，并与12只接受生理盐水注射的对照组兔子进行比较。在研究开始前和结束时采集血样。在治疗结束时获取心脏、肝脏和肾脏的组织样本，并对心脏进行组织学检查。在接受治疗的动物中发现了心脏病变，包括心肌纤维紊乱、肌溶解、间质和心内膜纤维化以及坏死，但对照组未出现这些病变。与对照组相比，接受治疗的动物血硒水平下降了20%，心肌组织硒水平下降了50%（P < 0.001）。相比之下，各实验组肝脏和肾脏中的硒水平没有差异。这些结果表明硒缺乏与抗精神病药物诱发的心脏病变之间可能存在关联。
