Distinct sympathoneural and cardiovagal domains of arterial baroreflex function in autonomic synucleinopathies

Figures

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  Figure 1. Baroreflex-sympathoneural indices across synucleinopathy groups. Individual values are shown for ten indices of baroreflex-sympathoneural function in Control subjects (gray) and in patients with the synucleinopathies pure autonomic failure (PAF, green), Parkinson disease with orthostatic hypotension (PD+OH, red), Parkinson disease without orthostatic hypotension (PD No OH, tan), cerebellar multiple system atrophy (MSA-C, magenta), and parkinsonian multiple system atrophy (MSA-P, blue). Panels show the following indices: (A) pressure recovery time (PRT), (B) ΔBPs during Valsalva Phase II, (C) log baroreflex area total, (D) fractional increase in plasma norepinephrine during orthostasis (FxΔNE Ortho), (E) BRS-A, (F) log baroreflex area III, (G) log baroreflex area II, (H) fractional increase in plasma DHPG during orthostasis (FxΔDHPG Ortho), (I) fractional change in forearm vascular resistance during orthostasis (FxΔFVR Ortho), and (J) fractional change in total peripheral resistance during orthostasis (FxΔTPR Ortho). Bars indicate mean values ± SEM. Horizontal brackets show comparisons between groups; numbers in italics show p values from Tukey’s post-hoc tests. Overall, the…

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  Figure 2. Baroreflex-cardiovagal indices across synucleinopathy groups. Individual values are shown for six indices of baroreflex-cardiovagal function in Control subjects (gray) and in patients with the synucleinopathies pure autonomic failure (PAF, green), Parkinson disease with orthostatic hypotension (PD+OH, red), Parkinson disease without orthostatic hypotension (PD No OH, tan), cerebellar multiple system atrophy (MSA-C, magenta), and parkinsonian multiple system atrophy (MSA-P, blue). Panels show the following indices: (A) increase in heart rate during the Valsalva maneuver (Inc. in HR Val), (B) baroreflex slope (Baroslope), (C) standard deviation of R–R intervals (SDRR), (D) log baseline low-frequency heart rate variability (log BL LF), (E) log baseline high-frequency heart rate variability (log BL HF), and (F) ΔHR/ΔBPs during orthostasis. Bars indicate mean values ± SEM. Horizontal brackets show comparisons between groups; numbers in italics show p values from Tukey’s post-hoc tests. Overall, the indices show reduced cardiovagal baroreflex function in the synucleinopathies, with the most consistent abnormalities in PAF and PD+OH and more variable changes in PD No OH and MSA.

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  Figure 3. Correlation matrix heatmap for indices of arterial baroreflex-sympathoneural function. Spearman correlation coefficients and associated p values are shown for ten indices of baroreflex-sympathoneural function across all subjects. Each cell displays the correlation coefficient and the corresponding p value; darker red shading and white text indicate cells where the p value is less than 0.01. The indices include both physiological and neurochemical measures. PRT denotes pressure recovery time during the Valsalva maneuver and BRS-A baroreflex sensitivity estimated from the ratio of the pressure recovery time to the decrease in systolic blood pressure during the Valsalva maneuver (BRS-A method). Log Baro. Area II and Log Baro. Area III are the logarithm of the baroreflex area relating R–R interval to systolic blood pressure during Phases II and III of the Valsalva maneuverand Log Baro. Area Total the logarithm of the total baroreflex area across the phases of the maneuver. ΔBPs Val Phase II denotes the change in systolic blood pressure during Phase II of the maneuver; FxΔFVR Ortho the fractional change in forearm vascular resistance during orthostasis, and FxΔTPR Ortho the fractional…

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  Figure 4. Correlation matrix heatmap for indices of baroreflex-cardiovagal function. Spearman correlation coefficients and associated p values are shown for six indices of baroreflex-cardiovagal function across all subjects. Each cell displays the correlation coefficient and the corresponding p value; dark blue shading and white text indicate cells where the p value is less than 0.01. Inc. in HR Val denotes the increase in heart rate during the Valsalva maneuver; Baroslope the baroreflex slope relating R–R interval to systolic blood pressure during the Valsalva maneuver; SDRR the standard deviation of R–R intervals during supine rest; log BL LF the logarithm of baseline low-frequency power of heart rate variability during supine rest; log BL HF the logarithm of baseline high-frequency power of heart rate variability during supine rest; and ΔHR/ΔBPs Ortho the ratio of the change in heart rate to the change in systolic blood pressure during head-up tilt at 90 degrees from horizontal. Overall, the matrix shows good agreement among several but not all cardiovagal indices, particularly between measures derived from heart rate variability and Baroslope.

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  Figure 5. Network representations of relationships among indices of arterial baroreflex-sympathoneural and baroreflex-cardiovagal function. The panels show force-directed networks (FDNs). Each circle represents one index, and the spatial arrangement of circles reflects the strength of correlations among indices across all subjects. Circle size is proportional to the summed absolute correlations of that index with the other indices, with larger circles representing variables that are more strongly associated overall with the rest of the network. Lines connecting circles represent correlations between indices; line thickness is proportional to the magnitude of the correlation coefficient, with thicker lines indicating stronger associations and thinner lines indicating weaker associations; solid lines indicate positive correlations and dashed lines indicate negative correlations. (A) Spearman FDN for baroreflex-sympathoneural indices; (B) Spearman FDN for baroreflex-cardiovagal indices; (C) Spearman FDN for combined sympathoneural and cardiovagal indices. Abbreviations: PRT, pressure recovery time during the Valsalva maneuver; ΔBPs Val Phase II, change in systolic blood pressure during Phase…