Closed-loop bioelectronic block of stellate ganglia reduces neurotransmitter release and improves recovery following programmed ventricular pacing

Figures

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  FIGURE 1. The surgical preparation and pacing protocol for the terminal experiments. The top portion of the plot shows the surgical setup and instrumentation for these experiments. For chronically infarcted animals, the site of the left anterior descending (LAD) artery occlusion is labeled, along with the resulting scar tissue. The bottom portion shows an example of the decremental programmed pacing protocol used in these experiments.

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  FIGURE 2. The above plots show the normalized NE current traces for each trial in both healthy and MI animals. The bolded traces represent the mean value at each timepoint. From left to right, there is the unblocked baseline trials (A) the 33% reduction controlled trials (B) and the 66% reduction control trials (C) In general, the current trajectories appear similar between the healthy and MI animals, aside from a single 66% reduction trial in a healthy animal, where the norepinephrine spontaneously plunged below the baseline soon after block was applied.

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  FIGURE 3. This plot shows the peak normalized current for each type of trial. For the healthy animals, the unblocked trials had the highest peaks, (median 112.5%), the 33% reduction trials were lower (median 81.8%) and the 66% reduction trials were the lowest (median 60.6%). The MI pigs followed the same order, with the unblocked trials having the largest peaks, (median 115.2%), the 33% reduction trials were lower (median 93.5%) and the 66% reduction trials were the lowest (median 82.3%).

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  FIGURE 4. The dashed box plots show the mean normalized current during the programmed pacing for each type of trial. In both healthy and MI animals, an increase in block lowered the mean NE currents measured. The solid box blots show the settling value for each type of trial, represented by the mean of the last 30 s of pacing. Similar to the mean values, an increase in block lowered the mean NE currents measured in both healthy and MI animals.

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  FIGURE 5. The above plot shows the mean blocking current delivered during the programmed pacing for both the healthy and MI animals, reported as a function of the block threshold (%BT). For both cases, the 66% reduction trials saw more blocking current than the 33% reduction trials, but the differences were not statistically significant.

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  FIGURE 6. The left plot (A) shows the change in left ventricular systolic pressure after pacing compared to the pre-pacing baseline. Significant differences were seen between MI and healthy animals at each setpoint, with the MI animals showing significant decreases in pressure following pacing, where healthy animals showed increases. There were also significant differences between the unblocked and 66% reduction trials in both MI and healthy animals. The right plot (B) shows the time after pacing where the LVSP returned to the baseline level. Responses were quite varied for most groups, but in MI animals the 66% decrease trials recovered significantly faster than the unblocked trials.

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  FIGURE 7. The left plot (A) shows the change in heart rate after pacing compared to the pre-pacing baseline. In general, the MI animals saw marginally smaller increases in heart rate after pacing, but no significant differences between any groups were seen. The right plot (B) shows the time after pacing where the heart rate returned to the baseline level. Responses were quite varied, and no significant differences were seen between any groups.