Cardiovascular alterations in rats with Parkinsonism induced by 6-OHDA and treated with Domperidone

Sci Rep. 2019 Jun 20;9(1):8965. doi: 10.1038/s41598-019-45518-z.

Abstract

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 patients 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 the narrowest 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology*
  • Disease Models, Animal
  • Domperidone / administration & dosage
  • Domperidone / adverse effects
  • Domperidone / pharmacology*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / adverse effects
  • Dopamine Antagonists / pharmacology*
  • Electrocardiography
  • Heart Rate
  • Humans
  • Immunohistochemistry
  • Male
  • Oxidopamine / adverse effects*
  • Parkinsonian Disorders / chemically induced*
  • Parkinsonian Disorders / complications*
  • Rats

Substances

  • Dopamine Antagonists
  • Domperidone
  • Oxidopamine