Impact of vericiguat on baroreflex-mediated sympathetic circulatory regulation: An open-loop analysis

Figures

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  Fig 1. A conceptual figure representing the baroreflex equilibrium diagram analysis. The baroreflex equilibrium diagram is obtained by plotting the neural arc (CSP–SNA relationship) and peripheral arc (SNA–AP relationship) on the plane of pressure versus SNA. The operating point of the carotid sinus baroreflex is determined from the intersection of the neural and peripheral arcs on the baroreflex equilibrium diagram.

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  Fig 2. An example time series obtained from one rat in the vericiguat protocol. CSP was changed in a stepwise manner with a step duration of 60 s. The input sequence was repeated and designated as S1 through S4. An increase in CSP decreased SNA, AP, HR, and m-AoF. CVP did not change significantly with the increase in CSP. From 1 min after the completion of S2, an intravenous administration of vericiguat was started and continued throughout the end of the protocol. The effect of vericiguat was evaluated in S4. Vericiguat decreased AP without significant changes in the SNA and HR responses. The CSP and HR are presented as 10-Hz resampled signals. The green and yellow lines in the SNA plot indicate 10-Hz resampled and 2-s moving averaged signals, respectively. The red and yellow lines in the AP plot indicate 100-Hz resampled and 2-s moving averaged signals, respectively. The m-AoF is presented as 2-s moving averaged signals. CSP, carotid sinus pressure; SNA, sympathetic nerve activity; AP, arterial pressure; HR, heart rate; m-AoF, mean aortic flow; CVP, central venous pressure.

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  Fig 3. Hemodynamic changes and baroreflex equilibrium diagram during administration of vericiguat. Group-averaged relationships of the total arc (A), CSP–HR relationship (B), neural arc (C), peripheral arc (D), SNA–SVR relationship (E), SNA–AoF relationship (F), CSP–CVP relationship (G), and the baroreflex equilibrium diagram constructed from the mean curve of the neural arc and the mean line of the peripheral arc (H) in the vericiguat protocol. In panels A–G, the data points are presented as mean ± SE values. In panel H, the operating point is displayed as mean ± SE values. P1 and P4 indicate the response range and the lower limit, respectively. The symbol * and ** indicate statistical significances at P < 0.05 and P < 0.01, respectively, by the Wilcoxon signed-rank test. In panel G, the P value was derived from the Wilcoxon signed-rank test. CSP, carotid sinus pressure; AP, arterial pressure; HR, heart rate; SNA, sympathetic nerve activity; SVR, systemic vascular resistance; AoF, aortic flow; CVP, central venous pressure; op-AP, AP at the operating point.

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  Fig 4. An example time series obtained from one rat in the SNP protocol. CSP was changed in a stepwise manner with a step duration of 60 s. The input sequence was repeated and designated as S1 through S4. An increase in CSP decreased SNA, AP, HR, and m-AoF. CVP did not change significantly with the increase in CSP. From 1 min after the completion of S2, an intravenous administration of SNP was started and continued throughout the end of the protocol. The effect of SNP was evaluated in S4. SNP decreased AP without significant changes in the SNA and HR responses. The CSP and HR are presented as 10-Hz resampled signals. The green and yellow lines in the SNA plot indicate 10-Hz resampled and 2-s moving averaged signals, respectively. The red and yellow lines in the AP plot indicate 100-Hz resampled and 2-s moving averaged signals, respectively. The m-AoF is presented as 2-s moving averaged signals. CSP, carotid sinus pressure; SNA, sympathetic nerve activity; AP, arterial pressure; HR, heart rate; m-AoF, mean aortic flow; CVP, central venous pressure; SNP, sodium nitroprusside.

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  Fig 5. Hemodynamic changes and baroreflex equilibrium diagram during administration of SNP. Group-averaged relationships of the total arc (A), CSP–HR relationship (B), neural arc (C), peripheral arc (D), SNA–SVR relationship (E), SNA–AoF relationship (F), CSP–CVP relationship (G), and the baroreflex equilibrium diagram constructed from the mean curve of the neural arc and the mean line of the peripheral arc (H) in the SNP protocol. In panels A–G, the data points are presented as mean ± SE values. In panel H, the operating point is displayed as mean ± SE values. P1 and P4 indicate the response range and the lower limit, respectively. The symbol * and ** indicate statistical significances at P < 0.05 and P < 0.01, respectively, by the Wilcoxon signed-rank test. n.s., not significant by the Wilcoxon signed-rank test; CSP, carotid sinus pressure; AP, arterial pressure; HR, heart rate; SNA, sympathetic nerve activity; SVR, systemic vascular resistance; AoF, aortic flow; CVP, central venous pressure; op-AP, AP at the operating point; SNP, sodium nitroprusside.