Advancements in Estimating Baroreflex Function Exploring Different Aspects of Autonomic Control of the Heart through the Sequence Technique T he arterial baroreflex plays a key role in blood pressure (BP) homeostasis, and its impairment may result in exaggerated blood pressure fluctuations and an in- creased risk of cardiovascular morbid events [1]. Given its pathophysiological relevance, arterial baroreflex function, and in particular baroreflex control of heart rate, is now widely assessed both in cardiovascular research and in a clinical setting [2]. Such an extensive interest has triggered a growing demand for tech- niques able to investigate the arterial baroreflex under different behavioral con- ditions, with no need of external surveil- lance or of interventions on the subject under investigation. Moreover, as the characteristics of baroreflex control have been reported to change over time [3], the increasing need is for methods able to as- sess such a regulatory function in a dy- namic fashion. Over the years, a number of techniques satisfying the above requirements have been developed. These techniques pro- vide dynamic estimates of the gain of baroreflex heart rate control—usually re- ferred to as baroreflex sensitivity (BRS)—through computer processing of BP and heart rate spontaneous beat-to- beat variability (Table 1). All these ap- proaches can be classified as “modern” techniques, to differentiate them from the “traditional” techniques which, con- versely, cannot estimate BRS under con- ditions of spontaneous behavior, nor can they yield information on the dynamical features of baroreflex cardiovascular reg- ulation (Table 2). Indeed, the “traditional” approaches have to be employed in a labo- ratory environment, and these provide only spot BRS estimates by evaluating the R-R interval (RRI; i.e., the reciprocal of the heart rate) reflex response to BP changes induced by external stimuli. Fur- ther details on these techniques may be found in [2]. Among the modern approaches for evaluating BRS, one of the most fre- quently employed is the sequence tech- nique [8]. This method is based on the computerized scanning of beat-to-beat se- ries of systolic (S)BP and RRI values in search of spontaneous sequences of three or more consecutive heart beats in which SBP progressively increases and, usually with a one-beat delay, RRI progressively lengthens (RRI+/SBP+ sequences) or, vice-versa, SBP progressively decreases and RRI shortens (RRI - /SBP - se- quences). The slope of the regression line between the SBP and RRI values included in each sequence is traditionally taken as a measure of BRS (a scheme of this method is shown in Fig. 1). A large number of these baroreflex sequences spontaneously occurs during daily life activities (approx. 80 per hour [9]), thus providing a detailed profile of BRS modulation over time. In this article, we focus on the method- ological basis of this technique. In partic- ular, by taking advantage of experimental data collected over the years, we explore the characteristics of the SBP and RRI patterns within each spontaneous se- quence. This analysis will be followed by methodological considerations aimed at clarifying the perspective from which the sequence technique evaluates BRS, as compared with other techniques. Finally, the latest enhancements of the sequence technique, leading to the quantification of other aspects of baroreflex function apart from BRS, will also be described. Underlying Concepts and Considerations Each of the above-mentioned sponta- neous RRI/SBP sequence is based on the joint occurrence of concordant monotonic changes in both SBP and RRI signals. In March/April 2001 IEEE ENGINEERING IN MEDICINE AND BIOLOGY 25 0739-5175/01/$10.00©2001IEEE ©1989-97 TechPool Studios, Inc. Marco Di Rienzo 1 , Paolo Castiglioni 1 , Giuseppe Mancia 2 , Antonio Pedotti 1,3 , Gianfranco Parati 4 1 LaRC, Centro di Bioingegneria, Fnd. Don C. Gnocchi and Politecnico, Milano 2 Ospedale S. Gerardo, Monza and Università di Milano-Bicocca 3 Dept. of Bioengineering, Politecnico di Milano 4 Istituto Scientifico San Luca, Centro Auxologico Italiano, Milano