Baroreflex control of muscle sympathetic nerve activity: a nonpharmacological measure of baroreflex sensitivity

Abstract

The sensitivity of baroreflex control of sympathetic nerve activity (SNA) represents the responsiveness of SNA to changes in blood pressure. In a slightly different analysis, the baroreflex threshold measures the probability of whether a sympathetic burst will occur at a given diastolic blood pressure. We hypothesized that baroreflex threshold analysis could be used to estimate the sensitivity of the sympathetic baroreflex measured by the pharmacological modified Oxford test. We compared four measures of sympathetic baroreflex sensitivity in 25 young healthy participants: the "gold standard" modified Oxford analysis (nitroprusside and phenylephrine), nonbinned spontaneous baroreflex analysis, binned spontaneous baroreflex analysis, and threshold analysis. The latter three were performed during a quiet baseline period before pharmacological intervention. The modified Oxford baroreflex sensitivity was significantly related to the threshold slope (r = 0.71, P < 0.05) but not to the binned (1 mmHg bins) and the nonbinned spontaneous baroreflex sensitivity (r = 0.22 and 0.36, respectively, P > 0.05), which included burst area. The threshold analysis was also performed during the modified Oxford manipulation. Interestingly, we found that the threshold analysis results were not altered by the vasoactive drugs infused for the modified Oxford. We conclude that the noninvasive threshold analysis technique can be used as an indicator of muscle SNA baroreflex sensitivity as assessed by the modified Oxford technique. Furthermore, the modified Oxford method does not appear to alter the properties of the baroreflex.

Fig. 1.

Example of a threshold diagram from a female participant. The individual circles represent the mean diastolic blood pressure in each 1-mmHg blood pressure bin. For each of these bins the percentage of heart beats associated with a burst is plotted against the mean of the pressure in that bin. The dotted line represents the diastolic blood pressure associated with 50% bursts (T₅₀). In this particular female the T₅₀ is 72 mmHg.

Fig. 2.

Threshold analysis of an individual male participants baroreflex sensitivity at baseline (solid line, black circles) and during a modified Oxford (Modox; dashed line, white circles). There were no changes in the sensitivity of the baroreflex (T₅₀: baseline, 82 mmHg, solid line vs. modified Oxford; 82 mmHg, dotted line).

Fig. 3.

Relationship of sympathetic baroreflex slope estimated by the modified Oxford method to the slope measured by the spontaneous baroreflex in 2-mmHg blood pressure bins (left, n = 18 participants) and the slope measured by the threshold method (right, n = 25 participants). The slope measured by the modified Oxford method was not related to the slope estimated by the spontaneous baroreflex method but was strongly related to the slope calculated by the threshold analysis. AU, arbitrary units.

Fig. 4.

Bland-Altman plots to predict the limits of agreement between the baroreflex slope measured by the modified Oxford method and the baroreflex slope estimated by the baroreflex threshold analysis (n = 25 participants). Left: fixed bias (solid line) between 2 methods (the mean difference between the 2 methods) and the dashed lines represent the 95% confidence limits. The bias is low when the slope of the modified Oxford is compared with the slope calculated from the baroreflex threshold analysis (bias = 0.4); therefore, both methods are producing similar results. Right: there is a proportional bias between the methods (the slope of the relationship between the difference between both methods and the mean of both methods is significant from 0, solid line). The dashed lines represent the prediction interval calculated from the slope of the regression line. These intervals suggest that 95% of all data points will lie within these limits.