Signal-averaged resting sympathetic transduction of blood pressure: is it time to account for prevailing muscle sympathetic burst frequency?

Abstract

Calculating the blood pressure (BP) response to a burst of muscle sympathetic nerve activity (MSNA), termed sympathetic transduction, may be influenced by an individual's resting burst frequency. We examined the relationships between sympathetic transduction and MSNA in 107 healthy males and females and developed a normalized sympathetic transduction metric to incorporate resting MSNA. Burst-triggered signal-averaging was used to calculate the peak diastolic BP response following each MSNA burst (sympathetic transduction of BP) and following incorporation of MSNA burst cluster patterns and amplitudes (sympathetic transduction slope). MSNA burst frequency was negatively correlated with sympathetic transduction of BP (r=-0.42; P<0.01) and the sympathetic transduction slope (r=-0.66; P<0.01), independent of sex. MSNA burst amplitude was unrelated to sympathetic transduction of BP in males (r=0.04; P=0.78), but positively correlated in females (r=0.44; P<0.01) and with the sympathetic transduction slope in all participants (r=0.42; P<0.01). To control for MSNA, the linear regression slope of the log-log relationship between sympathetic transduction and MSNA burst frequency was used as a correction exponent. In sub-analysis of males (38±10 vs. 14±4bursts/min) and females (28±5 vs. 12±4bursts/min) with high vs. low MSNA, sympathetic transduction of BP and sympathetic transduction slope were lower in participants with high MSNA (all P<0.05). In contrast, normalized sympathetic transduction of BP and normalized sympathetic transduction slope were similar in males and females with high vs. low MSNA (all P>0.22). We propose that incorporating MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.

Reply to Fadel et al.

“…In our view, these results demonstrate an important confounding factor of the signal-averaging technique, which can require normalization [resting MSNA burst frequency represents a proxy of the proportion of bursts occurring at higher BP levels (3)] or the incorporation of the BP responses to nonburst cardiac cycles to enable accurate physiological interpretations between individuals with differing MSNA. Reanalysis of our data (2) shows that the difference in BP responses between cardiac cycles with and without an MSNA burst (as a measure of sympathetic transduction) is unrelated to resting MSNA burst frequency (r 2 = 0.01, P = 0.22).…”

“…REPLY: We thank Dr. Fadel and colleagues (1) for their interest and commentary on our study of the relationships between measures of signal-averaged sympathetic transduction of blood pressure (BP) and resting muscle sympathetic nerve activity (MSNA) in healthy young adults and the development of a method for normalizing differences in MSNA burst frequency between individuals for sympathetic transduction analyses (2). We will address several important points raised in their Letter to the Editor and incorporate the results of our recent analysis showing the influence of BP oscillations on sympathetic transduction of BP (3).…”

“…Finally, we agree with Fadel and colleagues (6) that the signal-averaged sympathetic transduction technique represents a valuable tool to understand neurocardiovascular regulation both within and across different cohorts, to which they have made seminal contributions. Our recent work (2,3) has sought to better understand the limitations of the technique to aid in the physiological interpretation of data. Our analysis of normalizing for resting MSNA was also done to highlight the nonlinear nature of the relationship between sympathetic transduction of BP across a large range of resting MSNA levels.…”

Sympathetic transduction: let’s not forget about the physiology

“…In a recent issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Nardone et al (4) attempt to add to this emerging area of research by considering the potential influence of resting MSNA on sympathetic transduction. The authors propose that incorporating resting MSNA burst frequency into the calculation of sympathetic transduction will allow comparisons between participants with varying levels of resting MSNA.…”

“…In summary, we commend Nardone et al (4) on their attempt to examine the potential influence of resting MSNA on sympathetic transduction. There may indeed be an influence of resting MSNA, but we would argue that is physiology at its finest.…”