Cardiac and Autonomic Dysfunctions Assessed Through Recurrence Quantitative Analysis of Electrocardiogram Signals and an Application to the 6-Hydroxydopamine Parkinson's Disease Animal Model.

A classic method to evaluate autonomic dysfunction is through the evaluation of heart rate variability (HRV). HRV provides a series of coefficients, such as Standard Deviation of n-n intervals (SDNN) and Root Mean Square of Successive Differences (RMSSD), which have well-established physiological associations. However, using only electrocardiogram (ECG) signals, it is difficult to identify proper autonomic activity, and the standard techniques are not sensitive and robust enough to distinguish pure autonomic modulation in heart dynamics from cardiac dysfunctions. In this proof-of-concept study we propose the use of Poincaré mapping and Recurrence Quantification Analysis (RQA) to identify and characterize stochasticity and chaoticity dynamics in ECG recordings. By applying these non-linear techniques in the ECG signals recorded from a set of Parkinson's disease (PD) animal model 6-hydroxydopamine (6-OHDA), we showed that they present less variability in long time epochs and more stochasticity in short-time epochs, in their autonomic dynamics, when compared with those of the sham group. These results suggest that PD animal models present more "rigid heart rate" associated with "trembling ECG" and bradycardia, which are direct expressions of Parkinsonian symptoms. We also compared the RQA factors calculated from the ECG of animal models using four computational ECG signals under different noise and autonomic modulatory conditions, emulating the main ECG features of atrial fibrillation and QT-long syndrome.

Assessment of vitamin D and inflammatory markers profile in cardiac tissue on Parkinson disease animal model.

BACKGROUND: Cardiovascular dysfunctions are common non-motor symptoms in patients with Parkinson's disease (PD) that can result in reduced quality of life and even death. Research in animal models designed to characterize the pathological association between PD and cardiovascular abnormalities is still in its infancy. This study assessed the early impact of the nigrostriatal dopaminergic damage on cardiological features in the unilateral 6-OHDA rat model of PD. METHODS: Male Wistar rats received unilateral intrastriatal injections of 6-OHDA and sham rats were injected with saline. Animals were studied 15 days later. Immunohistochemistry was used for visualization of tyrosine hydroxylase (TH)-positive neurons in the nigrostriatal system. Electrocardiogram recordings of heart rate were performed in conscious rats. Heart levels of vitamin D, inflammatory cytokines and C-reactive protein were assessed through electrochemiluminescence immunoassay, quantitative reverse transcription PCR and turbidimetric method, respectively. RESULTS: We found a post-injury reduction of TH-immunoreactivity of approximately 45% in the substantia nigra pars compacta and 20% in the striatum. Heart rate reduction was found in 6-OHDA-lesioned rats as compared with sham counterparts. Reduced levels of vitamin D and increased levels of inflammatory factors (C-reactive protein, IL-6, TNF-α and TGF-ß) were detected in the heart tissue of PD rats in comparison with sham. CONCLUSION: Our findings suggest a link between cardiac tissue changes and cardiac functional changes early after the central dopaminergic damage induced by 6-OHDA. Knowledge of the cardiac abnormalities in the 6-OHDA model is critical in identifying future therapeutic targets and disease-modifying approaches for PD non-motor features.