Protective role of selenium supplementation against cardiac lesions induced by the combination of levomepromazine and risperidone in the rabbit.

Neuroleptics are a suspected cause of sudden death in psychiatric patients, especially in those with pre-existing cardiac lesions. As these lesions were previously shown to be associated with selenium (Se) deficiency, the aim of the present study was to evidence the possible protective effect of Se supplementation against cardiac lesions induced by the combination of the neuroleptic drugs levomepromazine and risperidone in the rabbit. Two groups of 6 rabbits were treated with 3 mg/kg of levomepromazine daily intramuscularly combined with 1 mg/kg of risperidone intramuscularly every other week for 3 consecutive months, and one group additionally received a solution of sodium selenite (2 microg/kg/day) intramuscularly during the whole treatment period. Furthermore, one group of six untreated animals was given the Se supplementation and another group of six control animals received saline daily. Blood samples were drawn before and at the end of the treatment period for the measurement of serum Se levels. At the end of the study, all animals were sacrificed and their hearts were removed for the measurement of tissue Se concentrations. In addition, the hearts were prepared for histopathological examination. A variety of cardiac lesions was found in the neuroleptics-treated animals without supplementation and to a lesser extent in the control and Se-supplemented untreated animals. Importantly, only rare cardiac lesions were observed in neuroleptics-Se-treated animals. The most striking differences in Se concentrations were noted in the myocardium: as compared to controls, there was a 43% reduction in neuroleptics-treated, but non-Se-supplemented animals (p < .01), at the end of the treatment period, whereas only a 14% reduction (p < .05) was noted in the neuroleptics-Se-treated animals. These results confirm that neuroleptics induce cardiac lesions associated with Se deficiency. Selenium supplementation markedly decreased the incidence and severity of neuroleptics-induced cardiac lesions and these findings may serve as a basis for further evaluation of the protective role of Se supplementation in neuroleptics-treated patients. However, Se supplementation in normal animals without Se deficiency was also shown to be cardiotoxic.

Cardiac lesions induced by neuroleptic drugs in the rabbit.

Sudden death seems to be more frequent following treatment with neuroleptic drugs in patients with pre-existing cardiac lesions, especially dilated and hypertrophic myocardiopathy. The present study was undertaken to confirm the hypothesis that myocardial lesions can be induced by neuroleptic drugs. Eight groups of 6 New-Zealand White rabbits were treated for 3 months: group I: controls (saline); group II: 15 mg/kg/day amisulpride; group III: 0.20 mg/kg/day haloperidol; group IV: 3 mg/kg/day levomepromazine; group V: 0.30 mg/kg/day olanzapine; group VI: 1.0 mg/kg risperidone, every 15 days; group VII: levomepromazine+haloperidol, same dose levels as single treatments; group VIII: levomepromazine+risperidone, same dose levels as single treatments. The hearts were immediately weighted and fixed, and paraffin sections were prepared and examined. Ventricular hypertrophy was observed following treatment with olanzapine and was still more marked with the combinations levomepromazine+haloperidol and levomepromazine+risperidone. Amisulpride and haloperidol induced necrotic lesions and levomepromazine, endocardial fibrosis. There was a lack of severe cardiac lesions following treatment with risperidone. The observed cardiac lesions can be compared to those seen in toxic myocarditis. These findings confirm the hypothesis that some neuroleptic drugs induce myocardial lesions. Further studies are warranted to demonstrate the effects of treatments of longer duration and the influence of pre-existing cardiac lesions.