In this study, we calculated the variability parameters of a rotenone-induced Parkinson's disease model to assess the impairment of cardiovascular autonomic function in the model of PD. Parkinson's disease is a complex condition that affects multiple organs throughout the body, with cardiovascular symptoms standing out among the non-motor symptoms26,27. Given the severity of cardiovascular-related symptoms, we used long-term ECG with Continuous blood pressure as a monitoring method, and then calculated variability parameters (blood pressure variability, heart rate variability) to determine the health status of the PD rat model. We found no significant changes in physiological status in the rotenone PD model, including no changes in heart rate, temperature, or mobility, indicating that unilateral stereotactic modeling of rotenone has a minor effect on physical function and does not cause serious harm to rats. Furthermore, central dopamine loss is similar to the pathophysiological relationship of Parkinson's disease in humans, and the effect of substantia nigra and striatal dopaminergic neuron loss on cardiovascular injury can be better explored by central rotenone injection.
HRV is used to assess the balance of sympathetic and parasympathetic nerves in cardiac autonomic nerves and to quantify cardiovascular autonomic function by calculating subtle changes in sinus rhythm per beat interval28,29. The severe imbalance in autonomic function reflected by the PD model's HRV is reflected by a decrease in total power of HRV, a decrease in RMSSD in the time domain, a decrease in the low-frequency component, and an increase in the high-frequency component in the frequency-domain analysis. RMSSD is the root mean square of the interpolated RR interval in time-domain analysis and is the primary indicator of heart parasympathetic innervation30–32. According to Fig. 2, the RMSSD of the experimental rats was lower than that of of the control rats, implying that the parasympathetic innervation of the heart in PD rats was affected compared to normal rats, with less volatility in the RR interval variation and more regular heartbeat rhythms, and this regularity represents to some extent the heart's reduced regulation. The signal was Fourier transformed in the frequency domain into several specific frequency bands, with the high frequency component (HF) reflecting parasympathetic activity and the low frequency component (LF) containing both sympathetic and parasympathetic effects. The normalization of the spectral components was represented on the autonomic nervous system balance in cardiac innervation. The decrease in nLF and increase in nHF in the experimental group reflected changes in sympathetic and parasympathetic innervation in the rotenone model rats, with parasympathetic innervation becoming more dominant and sympathetic innervation decreasing. The findings are consistent with the pathological changes in the autonomic nervous system caused by Parkinson's disease discovered by Ariza et al33 in a 6-OHDA animal model and by Alonso et al 13 in a clinical study, namely that PD causes significant time and frequency changes in HRV, a decrease in total power reflecting overall autonomic indicators, and a decrease in RMSSD reflecting parasympathetic innervation. The possible mechanism is an imbalance of cardiac sympathetic and parasympathetic innervation caused by the central nerve's influence on the vagus nerve dorsal nucleus, which is reached via vagal intestinal diffusion by the Lewy bodies34–37. Furthermore, the rats in the experimental group had low activity and dirty hair, confirming the autonomic innervation imbalance. In this study, telemetry was used to record long-duration ECG signals, which reduced interference in special states such as anesthesia and improved data accuracy when compared to other animal tests in which 5-min ECG signals were collected under anesthesia.
A combination of neural and humoral factors influence changes in arterial blood pressure, which can be easily measured and quantified. Blood pressure signals contain a wealth of physiological and pathological data. Traditional animal blood pressure measurements can only obtain systolic and diastolic blood pressure data at a specific point in time, but in this experiment, a pressure catheter was inserted into a blood vessel and continuous blood pressure was obtained using telemetry technology, allowing for long-term blood pressure monitoring. Circadian rhythm disturbances, upright hypotension, supine hypertension, and other symptoms are all symptoms of Parkinson's disease38,39. The model group had a statistically significant increase in mean arterial pressure, but not in systolic or diastolic blood pressure, which we conjecture is due to blood pressure fluctuations caused by changes in circadian rhythm in rats due to Parkinson's disease. Further research will focus on the analysis of circadian rhythm changes in the rotenone model rats and will extend the time of day when signals are collected. Figure 3 was primarily used to examine the variability of the continuous blood pressure signal. It has been demonstrated that two people with similar blood pressure can have different blood pressure volatility, and that continuously monitoring blood pressure to obtain blood pressure variability sequences can be used as a hidden indicator independent of other cardiovascular risk factors22,40. The standard deviation, coefficient of variation, and continuous variation of continuous blood pressure in experimental and control rats did not show significant differences in this study, but non-linear algorithms like sample entropy and detrended fluctuation analysis were used to sensitively identify changes in blood pressure fluctuations in the two groups of rats. This is in line with the findings of Fares et al41, who found that nonlinear analysis methods can more acutely capture indicators of subtle changes in intravascular pressure than traditional blood pressure variability analysis of standard deviation and coefficient of variation. In general, both sample entropy and detrended fluctuation analysis revealed changes in the blood pressure signal's nonlinear parameters, i.e., subtle changes in vascular pressure in PD rats were monitored in the pathological state, quantifying the biological system's instability in the pathological state42. The entropy value measures the irregularity of biological signals; the lower the entropy value, the more regular the signal, and the higher the entropy value, the more disordered the signal43,44. The relationship between reduced complexity and increased time series in biological systems is linked to the diseased state, with healthy organisms having higher complexity, that is, higher entropy values. This was corroborated in our investigation, where the sample entropy of diastolic and mean arterial pressure was significantly lower in the experimental group of rats than in the control group, while the sample entropy of systolic pressure showed no statistical differences. We hypothesized that Parkinson's disease mainly affects the volatility of diastolic blood pressure, i.e. the probability of generating new information in the diastolic blood pressure time series of PD rats is lower than that of normal controls, based on the clinical association of Parkinson's disease fatigue symptoms with lower levels of diastolic blood pressure45. The DFA values of systolic, diastolic, and mean arterial pressure in the continuous blood pressure signal of PD rats increased, showing that the continuous blood pressure signal's long time series correlation and predictability improved. Blood flow fluctuations in PD rats tended to be regular and predictable, reflecting the rotenone rat model's minor changes in hemodynamics. To summarize, we used a nonlinear approach to determine the variability of blood pressure fluctuations in PD rats versus normal rats, and future research will focus on changes in dynamic blood pressure in the early and late stages of dopaminergic neuronal degeneration, allowing us to investigate trends in blood pressure changes over time.
The current study confirmed that the rotenone stereotaxic model group experienced significant autonomic impairment. This was primarily seen as a reduction in total power in heart rate variability and an increase in high frequency components in normalized spectral analysis. In the absence of significant differences in arterial blood pressure and linear parameters, this study evaluated the variability of continuous blood pressure signals using nonlinear parameters such as sample entropy and detrended fluctuation analysis, perceptibly differentiating the changes in blood flow status in Parkinson's disease rats. This study used telemetry to record the cardiac and blood pressure signals of rats while they were awake, and it analyzed the functional changes of the cardiovascular and autonomic nervous systems in the Parkinson's disease state more precisely. Further research should concentrate on changes in blood pressure signals as the disease progresses, changes in nonlinear dynamics of blood pressure signals, and changes in cardiac autonomic function in the early stages of the disease. Simultaneously, in collaboration with clinical practice, we will design prospective studies to provide more reliable theoretical support for the study of cardiovascular autonomic function impairment in Parkinson's disease.