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.


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.
Diedrich
André
A
Autonomic Dysfunction Center, Vanderbilt University, Nashville, Tenn. 37232-2195, USA. andre.diedrich@vanderbilt.edu
Jordan
Jens
J
Shannon
John R
JR
Robertson
David
D
Biaggioni
Italo
I
D000368:Aged; D001341:Autonomic Nervous System / Q000187:drug effects*; D001342:Autonomic Nervous System Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004562:Electrocardiography; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D012791:Shy-Drager Syndrome / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D013057:Spectrum Analysis; D009435:Synaptic Transmission / Q000187:drug effects; D014294:Trimethaphan / Q000494:pharmacology
D002395:Catecholamines; D005730:Ganglionic Blockers; D014294:Trimethaphan