Research Paper ClinicalAutonomic Research 2000, 10:107-110 Invasive animal models indicate that the accelerative effects of the sympathetic nervous system on heart rate are highly de- pendent on the background level of vagal activity. A noninva- sive, parasympathetic chronotropic index (respiratory sinus ar- rhythmia) and a sympathetic chronotropic index (left ventricu- lar ejection time) were used to evaluate autonomic control of human heart rate. A strong interaction, previously called ac- centuated antagonism, was found. Sympathetic heart rate ef- fects were substantially smaller with high levels of vagal tone than with low vagal background activity. Furthermore, vagal effects became progressively stronger with increasing sympa- thetic background activity, demonstrating the predominance of parasympathetic control of human heart rate. This finding implies that changes in cardiac activity resulting from changes in sympathetic control cannot be interpreted accurately unless concurrent vagal activity is taken into account, as well. Key words: heart rate, parasympathetic, accentuated antagonism, respiratory sinus arrhythmia. Accentuated antagonism in the control of human heart rate Sebastian H.J. Uijtdehaage, Ph.D.,1 and Julian F. Thayer, Ph.D. 2 1Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles, California, USA; 2Department of Psychology, University of Missouri, Columbia, Missouri, USA Address correspondence and reprint requests to Julian F. Thayer, Ph.D., NIMGRC/LPC, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Tel: 410-558-8612; Fax: 410-558-8108 E-Mail: thayer@lpc.grc.nia.nih.gov ReceivedJuly 20, 1999; accepted as revised January 12, 2000 Heart rate (HR) is determined by intrinsic cardiac mecha- nisms and the joint activity of the sympathetic nerve and the parasympathetic (vagus) nerve at the sinoatrial node. An increase in sympathetic activity results in HR acceleration, whereas an increase in parasympathetic activity has a decel- erating effect. Usually, both branches of the autonomic ner- vous system are tonically active. However, their opposing effects are not algebraically additive. Instead, complex in- teractions have been demonstrated between the sympathetic and vagal determination of HR in animals [1,2]. For ex- ample, Levy and Zieske [1] systematically manipulated sym- pathetic and vagal stimulation in open-chest dogs, showing that an increase of sympathetic nerve firing caused HR ac- celeration. However, this HR increase was substantially sup- pressed when strong vagal activity occurred simultaneously. Furthermore, vagal deceleration effects were augmented with increased sympathetic background levels. This vagal predominance of HR control has been termed accentuated antagonism. Three basic aspects of heart activity may be distinguished: HR (chronotropic) properties, contractility (inotropic) properties, and conduction (dromotropic) properties. This conceptual separation of cardiac properties is often ignored but necessary to understand cardiac behavior. Each kind of activity has its own idiosyncratic relationship with the two divisions of the autonomic nervous system [3]. This article deals with chronotropic effects of autonomic influences, acknowledging the close inter-relationships among the three basic aspects of cardiac behavior. The purpose of this study was to demonstrate accentu- ated sympathetic-parasympathetic antagonism in humans with use of noninvasive and nonpharmacologic techniques. Respiratory sinus arrhythmia (RSA) is a widely accepted noninvasive index of parasympathetic chronotropic influ- ences [4,5,6]. A similar noninvasive index of sympathetic effects on HR is not yet available. Such an index is needed to assess sympathetic-parasympathetic interactions. There- fore, a secondary purpose was to search for such a sympa- thetic index. Materials and methods Five healthy college-aged subjects performed a multitude of tasks in a 3g2-hour session. All tasks were approved by the University Human Subjects Office. (1) The first was a re- action-time shock-avoidance task lasting 21/2 minutes. Sub- jects reacted to a visual stimulus on a monitor as rapidly as possible. Subjects were told that if their performance was "not good enough" they would receive a shock on the calf. No criteria of good performance were specified. Before the task, subjects were given sample shocks and determined themselves the maximum shock level they could tolerate. They were told that if they could avoid all shocks a $10 bonus would be offered. During the task, no actual shocks were administered. The monetary award was always given, regardless of the subject's performance. After the procedure was explained, all subjects gave written informed consent. The other tasks were (2) a hand grip task, in which the subjects squeezed a hand dynamometer at 40%, 30%, and 20% of maximum strength for 1 minute to produce varying levels of sympathetic activation caused by the well-known relationship between muscular work and HR [7]; (3) a cold pressor task, during which the subjects put their right arms in ice water for three 1-minute periods, separated by a 15- second recovery period; (4) a forehead cold pressor task, in which bags containing water of 35~ 20~ and 10~ were placed on the forehead for 1 minute each, causing varying degrees of the diving reflex [8]; (5) relaxation, during which 0959-9851 9 2000 LippincottWilliams & Wilkins 107