1604 November 2000, Part I PACE, Vol. 23 Introduction The measurement of the QT interval on elec- trocardiogram (ECG) represents a marker of global ventricular repolarization in vivo. 1,2 The QT inter- val duration is known to be sensitive to many and various factors. 3–5 The heart rate and, particularly, the duration of the preceding cardiac cycles are the primary sources of QT changes. 1,2,5–9 The au- tonomic nervous system (ANS), which can act di- rectly at the cellular level or indirectly through modulation of heart rate, is also an important source of QT changes. This has been well illus- trated by the prolongation of the QT interval dura- tion observed during sleep independent of heart rate that has been recognized as a consequence of the circadian changes in sympathovagal bal- ance. 3,4,9–11 Another important factor that can in- fluence the relationships between QT interval and the preceding cardiac cycle is the time delay re- quired for the QT interval to complete a full adap- tation after an instantaneous change in heart rate. This “QT delay” phenomenon has been docu- mented in animals and in humans and the time re- quired to achieve the full adaptation to a change in cardiac cycle length has been estimated to be be- tween 2 and 3 minutes in humans. 12 QT delay can influence the relationship between the QT inter- val and the preceding cardiac cycle length (QT- RR). Indeed, since a part of the QT rate adaptation follows RR changes with a time lag, a lower QT-RR relationship may be expected in the presence of a high beat-to-beat heart rate variability. Abnormalities of ventricular repolarization present several prognostic clinical implications in myocardial infarction, in long QT syndromes, or in sudden infant death syndrome, particularly as a marker of the propensity for cardiac arrhyth- mia. 13–16 Thus, investigating the respective contri- bution of interdependent factors such as heart rate, sympathetic tone, heart rate variability (HRV), and Influence of Sympathetic Heart Rate Modulation on RT Interval Rate Adaptation in Conscious Dogs PATRICK PLADYS,* PIERRE MAISON-BLANCHE,† BERNARD GOUT,‡ FABIO BADILINI,† ANTOINE BRIL,‡ and FRANÇOIS CARRɧ From the *Pediatric Department, Pontchaillou Hospital, Rennes, †Department of Cardiology and INSERM U127, Lariboisière Hospital, Paris, ‡SmithKline Beecham Laboratoires Pharmaceutiques, Cardiovascular Biology, Saint-Grégoire, and the §Medical Physiology Department and INSERM U127, Pontchaillou Hospital, Rennes, France PLADYS, P., ET AL.: Influence of Sympathetic Heart Rate Modulation on R Interval Rate Adaptation In Conscious Dogs. The objective was to test if changes in autonomic tone still influenced the RT-RR rela- tionship when full RT adaptation is completed, when heart rate is controlled, and when beat-to-beat vari- ability is abolished by atrial pacing. Eight dogs (8–11 kg) were chronically instrumented with atrial pacing electrodes. Digital ECG (1,000 Hz, 12 bits) were recorded from healthy conscious dogs during spontaneous sinus rhythm and during atrial pacing. The protocol was repeated before and after atenolol (2 mg/kg), pra- zosin (0.5 mg/kg), or atenolol 1 prazosin. A vocal incitation was used as sympathetic stimulation. Beat-to- beat quantitative analysis of the RT interval (from QRS apex to end of T wave) was correlated with the pre- ceding RR by linear regression. In spontaneous rhythm, atenolol increased RR (P , 0.001), RT (P , 0.001), and short-term heart rate variability (P , 0.01) and decreased RT-RR slopes (P , 0.001). Prazosin did not significantly modify any parameter. Sympathetic stimulation decreased RR (P , 0.001), RT (P , 0.05), and short-term heart rate variability (P , 0.01) and increased RT-RR slopes (P , 0.001). In atrial pacing, the RT- RR slopes were steeper during pacing than during spontaneous rhythm but were not modified by pharma- cological manipulation of the autonomic nervous system. During sinus rhythm the RT-RR relationship is increased by sympathetic stimulation and decreased by b-blockade. When heart rate modulation and the effects of the time delay in RT rate adaptation are abolished by atrial pacing, the influence of autonomic tone on RT rate adaptation disappears. (PACE 2000; 23[Pt. I]:1604–1610) QT, beta-adrenergic antagonists, autonomic nervous system, heart rate Address for reprints: François Carré, M.D., Laboratoire de Physiologie, Faculté de Médecine de Rennes. 2, Avenue du Professeur Léon Bernard, 35043 Rennes, France. Fax: (33) 299- 33-68-43; e-mail: patrick.pladys 6universal.fr Received August 3, 1999; revised January 28, 2000; accepted March 30, 2000. Reprinted with permission from JOURNAL OF PACING AND CLINICAL ELECTROPHYSIOLOGY , Volume 23, No. 11, Part I, November 2000 Copyright © 2000 by Futura Publishing Company, Inc., Armonk, NY 10504-0418.