Spike rate of multi-unit muscle sympathetic nerve fibers after catheter-based renal nerve ablation

Abstract

Patients with treatment-resistant arterial hypertension exhibited profound reductions in single sympathetic vasoconstrictor fiber firing rates after renal nerve ablation. In contrast, integrated multi-unit muscle sympathetic nerve activity (MSNA) changed little or not at all. We hypothesized that conventional MSNA analysis may have missed single fiber discharges, thus, obscuring sympathetic inhibition after renal denervation. We studied patients with difficult-to-control arterial hypertension (age 45-74 years) before, 6 (n = 11), and 12 months (n = 8) after renal nerve ablation. Electrocardiogram, respiration, brachial, and finger arterial blood pressure (BP), as well as the MSNA and raw MSNA signals were analyzed. We detected MSNA action-potential spikes using 2 stage kurtosis wavelet denoising techniques to assess mean, median, and maximum spike rates for each beat-to-beat interval. Supine heart rate and systolic BP did not change at 6 (ΔHR: -2 ± 3 bpm; ΔSBP: 2 ± 9 mm Hg) or at 12 months (ΔHR: -1 ± 3 mm Hg, ΔSBP: -1 ± 9 mm Hg) after renal nerve ablation. Mean burst frequency and mean spike frequency at baseline were 34 ± 3 bursts per minute and 8 ± 1 spikes per second. Both measurements did not change at 6 months (-1.4 ± 3.6 bursts/minute; -0.6 ± 1.4 spikes/second) or at 12 months (-2.5 ± 4.0 bursts/minute; -2.0 ± 1.6 spikes/second) after renal nerve ablation. After renal nerve ablation, BP decreased in 3 of 11 patients. BP and MSNA spike frequency changes were not correlated (slope = -0.06; P = .369). Spike rate analysis of multi-unit MSNA neurograms further suggests that profound sympathetic inhibition is not a consistent finding after renal nerve ablation.

Keywords: Arterial hypertension; blood pressure; microneurography; renal denervation.

Figure 1

Illustration of the spike detection method. Two stage kurtosis wavelet denoising technique for single spike detection. SWT= stationary wavelet transform, ISWT= inverse stationary wavelet transform

Figure 2

Individual changes in supine blood pressure and heart rate data obtained 6 months and 12 months following catheter-based renal nerve ablation compared to baseline measurements.

Figure 3

Original tracings of ECG, finger blood pressure (FBP), integrated (MSNA_i) and raw multi-fiber MSNA signals. The signal to noise ratio in the raw nerve signal is sufficiently high such that single sympathetic spikes can be discriminated. Several MSNA spikes occurred outside discernible bursts in the integrated MSNA signal. Arrows mark the beginning, maximum and the end of a burst in the integrated nerve signal. Stars mark single spikes.

Figure 4

Individual changes in burst frequency and burst incidence calculated from the integrated MSNA signal at 6 months and at 12 months following renal nerve ablation compared to baseline measurements.

Figure 5

Individual changes in mean, median and maximum beat to beat spike frequency calculated directly from the MSNA neurogram at 6 months and at 12 months after renal nerve ablation compared to baseline measurements.

Figure 6

Linear regression analysis between changes in supine systolic blood pressure and changes in mean beat to beat spike frequency at 6 months after renal denervation (left). Linear regression analysis between MSNA burst frequency and mean beat to beat spike frequency based on the pooled data from baseline, 6, and 12 months after renal nerve ablation (right).