Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects.

Autonomic nervous system activity is essential for regulation of ventricular repolarization (VR) and plays an important role in several arrhythmogenic conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated the VR response to pharmacologically modulated autonomic nervous system activity applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01-0.1 μg·kg(-1)·min(-1) isoprenaline (Iso) was infused at an increasing flow rate until three targeted heart rates (HR) were reached. After Iso washout, one intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed for each of the seven phases (including baseline 1 and 2). Furthermore, during the first 4 min following atropine, six periods of 10-s VCG were selected for subanalysis to evaluate the time course of change. The analysis included QRS, QT, and T-peak to T-end intervals, measures of the QRS and T vectors and their relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion decreased HR dependent parameters reflecting total heterogeneity of VR (T area) and action potential morphology (ventricular gradient). In contrast, Iso prolonged QT HR corrected according to Bazett and increased the T-peak to T-end-to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration after atropine was accompanied by a transient paradoxical QT prolongation and delayed HR adaptation of T area and ventricular gradient. In addition to the expected HR adaptation, the VR response to β-adrenoceptor stimulation with Iso and to muscarinic receptor blockade with atropine thus included alterations previously observed in congenital and acquired long QT syndromes, demonstrating substantial overlap between physiological and pathophysiological electrophysiology.