Fig 1.
Diagram depicting the main signals and the VNS parameters analyzed in this paper.
A) Representation of the left ventricular pressure signal (red), electrogram (EGM, green) and Vagus Nerve Stimulation signal (blue). B) Zoom displaying the main markers extracted from each beat: the inter-beat interval (RR interval) representing the chronotropic effect, the interval between the P-wave and the R-wave (PR inteval) used as a marker of the dromotropic effect and the maximum of the first of the Plv signal (). C) A typical VNS burst delivered synchronously with a cardiac beat (after a given delay Pdel), showing the VNS parameters studied in this paper.
Table 1.
Vagus nerve stimulation parameter ranges.
Fig 2.
Example of acute cardiac effects provoked by two different sets of VNS parameters.
Sequence was applied with parameters S1 = [0.8 mA, 2 pulses, 0.05 ms, 21.3 Hz, 125 ms], while sequence
with S2 = [0.4 mA, 2 pulses, 0.2 ms, 21.3 Hz, 125 ms].
Table 2.
RMSE of the best surrogate model for each cardiac effect and each sheep.
Fig 3.
Cardiac responses to different combinations of VNS parameters, estimated with a Gaussian process regression for sheep 1.
The chronotropic (), dromotropic (
) and inotropic (
) responses are shown in the first, second and third rows, respectively. Note the different scales of each colormap. The continuous black line represents a reference threshold of 5% variation with respect to the baseline value.
Fig 4.
Estimation of Sobol’s main and interactions indices for each VNS parameter on each cardiac effect.
A) chronotropic effect, B) dromotropic effect and C) inotropic effect. Total effects are equal to the sum of main and interactions effects (the whole color bar).
Fig 5.
Relative sensitivity of each VNS parameter and VNS parameter combination, according to Sobol’s first order and interaction indices.
A) chronotropic effect, B) dromotropic effect and C) inotropic effect. Only the five largest indices are shown, while the rest are summed together (“other”).
Table 3.
Sensitivity analysis results for chronotropic dromotropic and inotropic responses.
Main, total and interaction effects are expressed as percentage, along with their corresponding 95% confidence intervals [c.i. 95%], computed using a bootstrap approach.