Avaliação dos parâmetros cardiovasculares no modelo da Doença de Parkinson induzido pela 6-hidroxidopamina (6-OHDA) e tratados com domperidona
Data
2019-11-21
Autores
Rodrigues, Lais Damasceno 
Orientadores
Scorza, Fulvio Alexandre
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
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Resumo
Após a doença de Alzheimer, a doença de Parkinson (DP) é a segunda doença neurológica degenerativa progressiva mais frequente. Afeta tanto o sistema nervoso central quanto o sistema nervoso autônomo de maneira variável. Os sintomas cardiovasculares podem estar presentes antes mesmo dos primeiros sintomas motores. A administração de Levodopa em pacientes com DP provou fornecer algum grau de proteção neurológica. Esta droga, no entanto, causa efeitos colaterais, incluindo náuseas e vômitos, diminuídos pela administração de domperidona. Alguns exames de autópsias na DP não apresentaram uma causa de morte definida, e levaram alguns pesquisadores a sugerir o envolvimento da arritmia ventricular induzida pelos medicamentos. O objetivo do presente estudo foi determinar o impacto da dose máxima humana ajustada de Domperidona, em características cardiológicas em ratos Wistar. Domperidona foi administrada a ambos os modelos de parkinsonismo 6-hidroxidopamina e ratos Wistar controles. A análise quantitativa dos intervalos de variação do batimento cardíaco mostrou distribuição anormal significativa em ambos os grupos que receberam Domperidona, em comparação com os respectivos homólogos Sham. No entanto, a análise qualitativa das parcelas de Poincaré mostrou que os modelos de parkinsonismo com 6-hidroxidopamina que receberam domperidona tinham uma faixa mais estreita do batimento cardíaco e uma pior distribuição dos batimentos cardíacos em comparação com todos os grupos estudados, corroborando com a sugestão anterior de que a administração de Domperidona aos pacientes com DP provavelmente desempenhar um papel na morte súbita e inesperada neste grupo de pacientes.
After Alzheimer, Parkinson disease (PD) is the most frequently occurring progressive, degenerative neurological disease. It affects both sympathetic and parasympathetic nervous systems in a variable fashion. Cardiovascular symptoms are present in almost all stages of PD and narrower heart rate variability is the earliest sign. Administration of Levodopa to PD patients has proven to provide some degree of neurological protection. This drug, however, causes side effects including nausea and vomiting, lessened by the administration of Domperidone. Autopsies in PD led some researchers to suggest the involvement of the ventricular arrhythmia induced by Domperidone. The aim of the present study was to determine the impact of the adjusted human maximal dose of Domperidone, on cardiological features of Wistar rats. Domperidone was administered to both 6-hydroxydopamine Parkinsonism models and regular Wistar rats. Quantitative analysis of ranges of heart beat variation showed significant abnormal distribution in both groups receiving Domperidone as compared with respective sham counterparts. However, qualitative analysis of Poincaré plots showed that 6-hydroxydopamine Parkinsonism models receiving Domperidone had a narrowest of the full range of heart beat and the worst distribution heart beat ranges as compared with all study groups corroborating with previous suggestion that Domperidone administration to PD patients is likely to play a role in sudden unexpected death in this group of patients.
After Alzheimer, Parkinson disease (PD) is the most frequently occurring progressive, degenerative neurological disease. It affects both sympathetic and parasympathetic nervous systems in a variable fashion. Cardiovascular symptoms are present in almost all stages of PD and narrower heart rate variability is the earliest sign. Administration of Levodopa to PD patients has proven to provide some degree of neurological protection. This drug, however, causes side effects including nausea and vomiting, lessened by the administration of Domperidone. Autopsies in PD led some researchers to suggest the involvement of the ventricular arrhythmia induced by Domperidone. The aim of the present study was to determine the impact of the adjusted human maximal dose of Domperidone, on cardiological features of Wistar rats. Domperidone was administered to both 6-hydroxydopamine Parkinsonism models and regular Wistar rats. Quantitative analysis of ranges of heart beat variation showed significant abnormal distribution in both groups receiving Domperidone as compared with respective sham counterparts. However, qualitative analysis of Poincaré plots showed that 6-hydroxydopamine Parkinsonism models receiving Domperidone had a narrowest of the full range of heart beat and the worst distribution heart beat ranges as compared with all study groups corroborating with previous suggestion that Domperidone administration to PD patients is likely to play a role in sudden unexpected death in this group of patients.
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Citação
RODRIGUES, Laís Damasceno. Avaliação de parâmetros cardiovasculares no modelo da doença de Parkinson induzido pela 6-hidroxidopamina (6-OHDA) e tratados com Domperidona. 2019. 106f. Tese (Doutorado em Neurologia e Neurocirurgia) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2019.