Toward understanding respiratory sinus arrhythmia: Relations to cardiac vagal tone, evolution and biobehavioral functions
Introduction
Respiratory sinus arrhythmia (RSA) is a cardiorespiratory phenomenon characterized in mammals by heart rate (HR) or R-R interval (RRI) fluctuations that are in phase with inhalation and exhalation. Typically, HR accelerates during inspiration and slows down during expiration, but the exact phase relationship between respiratory and HR oscillations is dependent upon the prevailing respiration rate (Eckberg, 1983). Furthermore, even when autonomic tone remains stable, the amplitude of these rhythmic HR fluctuations (i.e. the magnitude of RSA) is greatly dependent upon both respiratory frequency and depth of ventilation (i.e. tidal volume; Hirsch and Bishop, 1981). The central, neural, humoral and mechanical feedback mechanisms that together generate RSA are a complex of integrated respiratory and cardiovascular responses (Grossman, 1983, Jordan and Spyer, 1987, Spyer, 1990). Therefore, RSA must be conceptualized as a phenomenon that directly results from the interaction between the cardiovascular and respiratory systems.
RSA has been shown to importantly reflect rhythmic waxing and waning of cardiac vagal efferent effects upon the sinoatrial node and, therefore, HR (Eckberg, 2003, Hedman et al., 1995b). The relationship between RSA and vagal control of HR has generated great interest among scientists who wish to explore and exploit noninvasive estimates of cardiovascular autonomic control. Along a related line, evidence that RSA magnitude in humans is sometimes predictive of both physiologic and psychological morbidity has also engendered research focused upon using RSA more as a marker of risk than as an index of discrete parasympathetic cardiac control (e.g. Bigger et al., 1992, Hayano et al., 1990, Janszky et al., 2004, Kluge et al., 1988, Nishimura et al., 2004).
Whatever the basic motivation for investigation, a firm understanding of what RSA is – and what RSA is not – would seem essential. All too commonly, a thorough grasp of RSA appears missing in the literature, and this has led to contradiction, confusion, misinterpretation and misattribution with respect to research findings and appropriate methods of measurement and analysis. The major purposes of this article are (1) to clarify the nature of RSA, (2) to elucidate certain misconceptions regarding RSA, and (3) to elaborate upon a new theoretical model that integrates RSA and biobehavioral functioning. In this model, RSA plays a significant role in coordinating physical energy requirements and continuously changing behavioral activities.
RSA – in addition to being simply employed as a cardiac vagal index – has become embedded in a theoretical framework of evolutionary, biological and psychobiological adaptation. Therefore, we will address both proximal concerns about its accuracy as a parasympathetic measure and broader aspects of its functional roles and its evolutionary origins in non-mammalian vertebrates. Specifically, we will discuss the biological function that RSA is likely to serve in coordinating and maintaining interplay between the respiratory and cardiovascular systems, which are together responsible for meeting metabolic demands over a range of highly variable internal and external conditions. Both respiratory and cardiovascular processes are responsive not only to gross metabolic demands but also to levels of alertness and, in humans at least, different types of emotion, mental activity and arousal (and the latter may only minimally or not at all change metabolism). Coupling of respiratory and cardiovascular systems, consequently, are likely to be pertinent to psychological and behavioral variations, as well as physiological state.
Our arguments fall under two themes: (1) clarification of the relationships between RSA and vagal tone in mammals and particularly humans, and (2) the evolution of central, vagal control of cardiorespiratory interactions in vertebrates. With respect to evolutionary issues, we will also critique the polyvagal theory (Porges, 1995), a currently popular view based upon assumptions about the evolution of the autonomic nervous system. The polyvagal theory attempts to introduce an evolutionary perspective into relations between parasympathetic activity and behavior and to explain situations in which changes in RSA clearly do not correspond to alterations in vagally mediated HR (i.e. cardiac vagal tone; Porges, 1995, Porges, 2001, Porges, 2003b). The theory maintains that RSA is generated in functionally distinct vagal systems that first evolved in the brainstem of mammals (Porges, 1995, Porges, 2003b). In recent years, this theory has been expanded to encompass a wide range of postulates regarding physical, psychophysiological and even social functioning in humans (e.g. Porges, 2003b, Sahar et al., 2001).
The following six points will guide the structure of our presentation:
- 1.
Respiratory parameters of rate and volume can confound relations between RSA and cardiac vagal tone.
- 2.
Although within-subject relations between RSA and cardiac vagal control are often strong (when properly measured), between-subject associations may be relatively weak.
- 3.
RSA measurement is strongly influenced by concurrent levels of momentary physical activity, which can bias estimation of individual differences in vagal tone.
- 4.
RSA amplitude is affected by beta-adrenergic tone and may not be a pure vagal measure.
- 5.
RSA and cardiac vagal tone may dissociate under certain circumstances.
- 6.
Basic assumptions of the polyvagal theory regarding RSA are at odds with current knowledge of the neuroanatomical and functional evolution of cardiac vagal control.
RSA can be quantified in a number of different ways, most commonly including spectral analysis, time-domain peak-valley analysis or application of a band-pass filter. Units of measurement can also consequently vary. For time-domain measures, RSA is typically estimated in ms (e.g. the inspiratory–expiratory difference in RRI). With spectral analysis and other frequency-domain approaches, the variation of RRI occurring within the range of the respiratory frequency is estimated; thus ms2 is frequently employed, consistent with usual statistical units of variance. Often RSA measures are logarithmically transformed to normalize distribution, but this is not always the case. Because different methods are almost perfectly correlated with each other when properly employed (Grossman et al., 1990b), we will not detail quantification methods when reviewing the literature, except when it might be pertinent to a specific topic. A fuller treatment of measurement issues is beyond the scope of this article.
Section snippets
Respiratory confounds in RSA estimation of cardiac vagal tone
Numerous studies have documented the effects upon RSA of voluntary and spontaneous changes in respiration rate and tidal volume under steady-state conditions and during mental tasks. Steady state, in this context, connotes conditions during which metabolic activity and autonomic tone remain largely constant. A sample of these studies include the following: Ahmed et al., 1982, Ahmed et al., 1986, Althaus et al. (1998), Angelone and Coulter (1964), Badra et al. (2001), Ben Lamine et al. (2004),
Individual differences in vagal tone may not always be reflected by variations of RSA
Studies validating RSA as a within-individual index of cardiac vagal tone have shown RSA to decrease proportionately to levels of atropine-induced cardiac vagal withdrawal. Along a different line, individual differences in cardiac vagal tone among humans are defined as the decrease in mean RRI (ms), produced by complete vagal blockade using atropine or some other vagolytic drug under basal conditions. In other words, cardiac vagal tone is operationalized as the difference between the average
Concurrent physical activity alters cardiac vagal tone and RSA
Recent evidence (Bernardi et al., 1996, Grossman et al., 2004) shows that accurate estimation of RSA is seriously biased by variations in concurrent physical activity. Heart rate during mild-to-moderate change in physical activity, characteristic of normal variations of daily activity, is predominantly under parasympathetic control (Boushel et al., 2001, Ekblom et al., 1972, Epstein et al., 1965, Grossman et al., 1991, Hopkins et al., 2003, Janicki et al., 1996, Maciel et al., 1986, O’Leary and
RSA is affected by sympathetic tone and may not be a ‘pure’ vagal index
As previously mentioned, within-individual validation studies of RSA are based upon evidence of changes in RSA during progressive pharmacological blockade of cardiac parasympathetic control (Ali-Melkkila et al., 1991, Coker et al., 1984, Dellinger et al., 1987, Hayano et al., 1991, Julu and Hondo, 1992, Medigue et al., 2001, Pyetan et al., 2003, Raczkowska et al., 1983, Scheinin et al., 1999). In almost all studies, an exponential reduction of RSA (quantified in different ways) is found as HR
RSA and cardiac vagal tone can dissociate under certain circumstances
There is evidence that RSA magnitude can sometimes dissociate from cardiac vagal tone, even under conditions of no apparent sympathetic–vagal interaction and when respiration is controlled. One example replicated in several studies is when extreme levels of cardiac vagal tone are provoked by pharmacological enhancement of the cardiac baroreflex (Goldberger et al., 1994, Goldberger et al., 1996, Goldberger et al., 2001). The baroreflex is a cardiovascular feedback system with a primary function
A critique and an alternative to the polyvagal theory
As stated earlier, the polyvagal theory was first proposed in 1995 (Porges, 1995, Porges, 2001, Porges, 2003b) as an attempt to (a) introduce an evolutionary perspective into relations between parasympathetic activity and behavior (possibly on the basis of a phylogenetic overview of vagal control of the heart in vertebrates reviewed by Taylor, 1994, as suggested by Medigue et al., 2001), and (b) to explain situations in which changes in RSA clearly do not correspond to alterations in vagally
Acknowledgements
Preparation of this article was partially supported by a grant from HRCA Research and Training Institute, Boston MA, U.S.A. We would like to thank Dr. Frank H. Wilhelm for discussion and comments, as well as all reviewers for their remarks.
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