Modulation of QT interval during autonomic nervous system blockade in humans

Background-It is thought that the autonomic nervous system modulates QT interval, but traditional autonomic blockade combining propranolol and atropine has produced conflicting results. We used the alternative approach of interrupting neurotransmission at the level of autonomic ganglia to determine its effect on the QT interval. Methods and Results-We infused trimethaphan at increasing doses (0.5 to 10 mg/min IV) while monitoring heart rate, heart rate variability spectra, QT interval, and blood pressure in 10 normal volunteers, 9 patients with multiple system atrophy (MSA), and 8 patients with pure autonomic failure (PAF). The QT interval was corrected for heart rate using Bazett's formula (QTc). Patients with PAF had very low heart rate variability and a prolonged QTc at baseline (465 +/- 8 ms) compared with patients with MSA (448 +/- 6 ms) and normal subjects (432 +/- 6 ms). In normal subjects, trimethaphan dose-dependently prolonged QTc (to 469 +/- 7 ms), decreased RR interval (995 +/- 45 to 670 +/- 35 ms), and abolished heart rate variability. In MSA patients, trimethaphan also prolonged QTc (to 463 +/- 7 ms) and reduced heart rate variability but did not significantly change RR interval (from 813 +/- 38 to 801 +/- 39). Conclusions-Autonomic blockade prolongs QT interval in normal subjects to a similar duration as in PAF patients. Furthermore, blocking residual autonomic tone in PAF patients is associated with a further increase in QT interval length. Patients with MSA have greater residual sympathetic tone and greater prolongation of the QT interval during ganglionic blockade than PAF patients.