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Variability of human vagal baroreflex responses
In ‘steady-state’ resting humans, baroreflex gain fluctuates hugely and rhythmically at very low frequencies
Features
Variability of human vagal baroreflex responses
In ‘steady-state’ resting humans, baroreflex gain fluctuates hugely and rhythmically at very low frequencies
Features
Dwain L Eckberg (1) & Tom A Kuusela (2)
1: Departments of Medicine and Physiology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center and Medical College of Virginia at Virginia Commonwealth University, Richmond, VA, USA
2: Department of Physics, University of Turku, Turku, Finland
https://doi.org/10.36866/pn.64.26
The arterial baroreflex occupies a central position in physiology: in healthy people, ever-present arterial pressure fluctuations lead to nearly instantaneous, usually reciprocal, changes of vagal and sympathetic neural outflows, which in turn modulate function of the heart and blood vessels.
Before 1969, there was no quantitative way to gauge the effectiveness of human baroreflex control. However, in that year, Smyth, Sleight & Pickering (1969) reported that brief systolic pressure elevations following bolus intravenous pressor injections provoke parallel prolongations of the intervals between heart beats. The regression of cardiac responses on pressure changes yields a slope, expressed in ms mmHg-1, which represents the ’gain’ of the vagal, or heart rate, portion of a subject’s baroreflex responses. Subsequent research (Bertinieri et al. 1985; Fritsch et al. 1986) showed that baroreflex gain also can be calculated from simple regression analysis of (small) spontaneously-occurring systolic pressure and heart period changes.
Wesseling and Settels (1985) mused about a conundrum that besets baroreflex research: If highly sensitive (Eckberg, 1977) baroreflex mechanisms are functioning properly, why is blood pressure so variable? We sought answers to this question by analysing the baroreflex function of supine healthy young adults on three separate days, using a cross-spectral method (Badra et al. 2001) which is based on correlations between power spectra of spontaneously-occurring systolic pressure and heart period changes. We estimated baroreflex gain over 15 s windows, moved every 2 s through 20 min periods of frequency- and tidal volume-controlled breathing (Eckberg & Kuusela, 2005).
Figure 1 shows an example of our results. The top and middle left panels indicate that this resting subject, who was to all outward appearances in a ‘steady-state’, was actually changing profoundly: for unknown reasons, his blood pressure, heart period (R-R intervals), and R-R interval variability increased steadily. The lowest left panel indicates that, during a 19 min period, this subject’s baroreflex gain, estimated from baroreflex sequences [red (Bertinieri et al. 1985; Fritsch et al. 1986)] and cross-spectra (black), more than doubled. Cross-spectral baroreflex gain fluctuated profoundly and ranged from 5 to 68 ms mmHg-1, a 14-fold difference! The right panel of Fig. 1 indicates that baroreflex fluctuations were periodic, with a peak frequency of about 0.009 Hz, or one cycle every 110 s.
Although other volunteers did not have such a striking steady increase of baroreflex gain, they all had major fluctuations of baroreflex gain. In the nine subjects studied, minimum, mean, and maximum baroreflex gain averaged 5, 18, and 55 ms mmHg-1, and the ratio of maximum to minimum baroreflex gain ranged from 4 to 35 (average: 14). The centre frequency of baroreflex fluctuations averaged 0.011 Hz, or about one cycle every 90 s. Thus, baroreflex gain periodicity falls in the very low [arbitrarily, 0.003 to 0.05 Hz (Berntson et al. 1997)] frequency range.
Figure 2 provides a different perspective on variability of baroreflex gain. In this and all other subjects, baroreflex distributions were skewed to the right, such that all subjects experienced infrequent, but major, augmentations of gain above their more prevalent levels. This figure also illustrates heretofore unrecognized complexities of human baroreflex function; it documents major differences in the distributions of baroreflex gain from day to day. Although this subject’s average baroreflex gain on days 2 and 3 were similar, 52 and 45 ms mmHg-1, their distributions were vastly different. Baroreflex gain was concentrated at lower levels on Day 2 than Day 3.
Figure 3 suggests that fluctuations of baroreflex gain may have functional significance. In these two. and several other, subjects, spikes of baroreflex gain (shown in red) seemed to occur in response to troughs of blood pressure – that is, brief pressure reductions ratcheted up baroreflex responsiveness. The right panels of Fig. 3 show the reverse side of the same coin. Here, systolic pressure was signal-averaged on average baroreflex gain (black), and at 2, 4, 6, and 8 mmHg ms-1 below the average (illustrated by gradations of gray from the highest (lightest), to the lowest (darkest) level of baroreflex gain. These data suggest that reductions of baroreflex gain are followed by elevations of arterial pressure.
These findings may have clinical significance. Patients with cardiovascular diseases have reduced vagal baroreflex gain in proportion to the severity of their diseases (Eckberg et al. 1971). Moreover, the prognosis of cardiac patients is poor when vagal baroreflex responses (La Rovere et al. 1998) or vagally-mediated heart rate fluctuations (Bigger Jr et al. 1992) are low. Subnormal heart rate variability at very low frequencies is particularly ominous. Our research provides a significant link between prognostically important baroreflex gain and prognostically-important very low frequency heart rate variability. The import of this association is unknown; however, it may be that cardiac patients do not have the ‘baroreflex reserve’ we report in healthy people, and thus may inadequately mount reflex responses to the major haemodynamic challenges that occur in daily living.
In conclusion, our work shows that in ostensibly ‘steady-state’ resting healthy people, vagal baroreflex responsiveness fluctuates in a major way at very low frequencies. These results suggest that the key dimension of time should be included in characterizations of human baroreflex function.
Acknowledgements
This work was supported by the National Institutes of Health, the Department of Veterans Affairs, and the National Aeronautics and Space Administration.
References
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