Autonomic integration: the physiological basis of cardiovascular variability

Blood pressure (BP) and heart rate (HR) are continually varying. The nervous mechanisms behind this variability have been studied extensively in non-human animal models (for reviews, see Eckberg & Sleight, 1992). Since the 1980s, the combined availability of non-invasive blood pressure measurement by the Penaz-Wesseling Finapres, and more and more powerful computers in the laboratory, have revived research into prevalence and physiological meaning of this variability in humans. When Fourier analysis was applied to analysis of BP variability (BPV) and HR variability (HRV), two frequency peaks stood out: one around the respiratory frequency and one around 0.1 Hz, or one oscillation in 10 s. These frequencies had been observed in blood pressure recordings before, actually over 130 years ago: Traube-Hering waves (coupled to respiration) and Mayer waves, the 0.1 Hz and slower oscillations. In the earlier research it had been established that oscillating sympathetic activity causes the Mayer waves in blood pressure. The respiration-coupled blood pressure oscillations were partly explained by mechanical effects of respiration and possibly by the vagally induced heart period oscillations coupled to respiration, known as respiratory sinus arrhythmia (RSA) (Eckberg & Sleight, 1992). Due to the easy availability of ECG recordings, heart rate oscillations have extensively been studied, much more so than blood pressure oscillations. In this field of research the idea was put forward that the 0.1 Hz oscillation in HRV, also called low frequency or LF, might be used as indicator of sympathetic activity. The respiratory (high frequency or HF) frequency in HR must be due to vagal activity, the vagus nerve being the only one that can make HRV follow at the respiratory rate; atropine also completely blocks RSA. It was but one step to suggest that the relative amounts of LF and HF HRV gave an impression of the balance between sympathetic and parasympathetic (vagal) outflow to the heart. Indeed, on many occasions where one would expect the balance to shift either way, the LF/HF ratio shifted similarly, even though it is common knowledge that atropine not only blocks HF but most of LF as well, demonstrating that both peaks in HRV are due to (mainly) vagal activity. A review of this theory and the arguments is given by Camm et al. (1996). This leaves a discrepancy: why would the LF/HF HRV ratio have a relation to the sympathetic/vagal outflow at all? The answer lies in the baroreflex: LF HRV is riding on a blood pressure oscillation. That, too, explains the phase relationship: blood pressure is leading the HR wave. The basis of this particular oscillation is, still, an unsettled matter. In this issue of The Journal of Physiology, Cooke et al. (1999) have very carefully investigated the prevalence of LF oscillations in healthy test humans who were subjected to graded passive orthostatic tilt on a tilt table. Efferent sympathetic activity, measured directly from the peroneal nerve, increased in proportion to the orthostatic load. However, in spite of large changes in baroreceptor loading and accompanying nerve traffic, the frequency of the LF band did not change at all. In the view of the authors, this pleads against the current theory for the origin of LF: up until now, many shared the view that this oscillation found its origin in the slowness of the baroreflex feedback to changes in peripheral resistance (resonance theory). This was supported by computer simulations of the cardiovascular control system and by other supporting evidence (DeBoer et al. 1987). Cooke et al. (1999) are inclined to put the origin of LF oscillations in some pacemaker, possibly in the CNS, rather than in the baroreflex. A comparable, unsettled matter is the origin of RSA. One explanation has been to see it as a baroreflex phenomenon: BP changing mechanically by the respiratory act, and HR following at the speed of vagal control, within the same beat (DeBoer et al. 1987). Another explanation would place the origin of RSA in the CNS, where co-activity of the vagus nerve with respiratory activity would drive HR in the same frequency as respiration (Taylor & Eckberg, 1996). Careful analysis of the phase relationships between respiratory oscillations in HR and BP should give the answer: is HR leading, or is BP?Cooke et al. (1999) have dealt with this issue as well: their analysis yields a phase advance for HR compared with BP changes. A comparable phase advance had been found earlier, by slightly different (Fourier) analysis methods (DeBoer et al. 1987). However, this had led those authors to give the advantage to BP, favouring the baroreflex hypothesis. The basic problem here is how one turns essentially discontinuous signals (systolic pressure values, heart period durations) into continuous ones that are input into the Fourier analysis. This calls for a meta-analysis of methods and results, rather than more experiments. The study by Cooke et al. (1999) has been one of the most carefully executed experimental studies in literature to date, so the final answer should be at hand. Where does this leave the LF/HF ratio as a measure for sympatho-vagal balance? From the Cooke et al. (1999) paper we learn how LF BP increases at increasing orthostatic stress. At the same time respiration-related vagal activity decreases, resulting in less HF HRV and almost unchanged LF HRV. The net effect is that LF/HF HRV, indeed, would shift as predicted. But then, so what? One may wonder if we should put much more effort in to what is clearly an epiphenomenon of basic processes in central cardiovascular control. The paper by Cooke et al. (1999) has probably not put an end to LF/HF HRV computations, but sends a clear warning sign to all who take its physiology seriously.