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

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.

Sudden death in a rat model of Parkinson's disease

“…However, none of the currently available animal models can completely reproduce the clinical characteristics of PD (21), although the unilateral 6-OHDA model used in the present study remains the most widely used model for experimental studies of PD in rats (22,23). Importantly, the immunohistochemical and cardiovascular data demonstrated here are consistent with previous studies of Parkinsonism in the unilateral 6-OHDA animal model of PD, suggesting that the rats were adequately lesioned (7,8,10,19,22).…”

“…These studies demonstrated that several ECG parameters reflect autonomic dysfunction or disease progression, strongly suggesting that clinicians should pay more attention to ECG abnormalities when treating patients with PD (3,(12)(13)(14). From an experimental point of view, several authors have also described cardiovascular changes in PD animals, which could be directly linked to cases of sudden death (7)(8)(9)(10). Thus, a recent study conducted by our research group showed that animals subjected to 6-OHDA showed a reduction in HR and greater variability of heartbeats using the Poincaré plot technique (10), which allows us to gain new insights into the dynamics of cardiac neural mechanisms (15).…”

“…In this context, the 6-hydroxydopamine (6-OHDA) model continues to constitute a classic animal model of PD in rats that has contributed to our current knowledge about motor and biochemical dysfunctions in PD (6). Importantly, several studies have also provided significant evidence that the 6-OHDA animal model can also be used to assess cardiovascular and autonomic changes, mimicking those found in patients with PD (7)(8)(9)(10). Considering the relevance of this model, we detected a case of a Wistar rat subjected to 6-OHDA that died suddenly, and the event was recorded during routine electrocardiogram (ECG) monitoring.…”

“…Another important point is that independent of the site of injection, the 6-OHDA-induced dopamine depletion appears to be a valuable model to investigate clinical PD manifestations and gain more insight into the systemic abnormalities observed in this neurodegenerative disease (7)(8)(9)(10)19,20). Both the unilateral and bilateral 6-OHDA models have their advantages and disadvantages (20,21).…”

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

“…In addition to impaired voluntary movements, 6-OHDA-injured rats exhibit a variety of nonmotor disturbances [ 17 ]. Some studies have shown that 6-OHDA-treated rats have lower patterns of HR and HRV than their control counterparts [ 18 , 19 , 20 ]. Knowledge of the pathological dysfunctions in an animal model is critical for recognizing prospective therapeutic targets as adjunctive therapies aimed at multiple levels of pathology are required in PD.…”