Published Online
on May 23, 2005

A more recent version of this article appeared on May 31, 2005

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Submitted on August 4, 2004
Revised on February 7, 2005
Accepted on February 16, 2005

Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome

Satish R. Raj MD^*, Bonnie K. Black RN, NP, Italo Biaggioni MD, Paul A. Harris PhD, and David Robertson MD

From the Autonomic Dysfunction Center, Divisions of Clinical Pharmacology (S.R.R., I.B., D.R.) and Cardiovascular Medicine (B.K.B.), Departments of Medicine, Pharmacology (S.R.R., I.B., D.R.), Neurology (D.R.), and Biomedical Engineering (P.A.H.), Vanderbilt University, Nashville, Tenn.

^* To whom correspondence should be addressed. E-mail: satish.raj{at}vanderbilt.edu.

Background--Postural tachycardia syndrome (POTS) induces disabling chronic orthostatic intolerance notable for an excessive increase in heart rate that occurs on standing. Many current therapeutic strategies focus on sympatholysis, but the alternative strategy of enhancing cardiovagal tone has not been studied. The objective of this study was to test the hypothesis that acetylcholinesterase inhibitors will attenuate the tachycardia and improve symptom burden in patients with POTS.

Methods and Results--Seventeen patients with POTS underwent acute drug trials of pyridostigmine 30 mg orally and placebo, on separate mornings, in a randomized crossover design. Blood pressures, heart rate, and symptoms were assessed while patients were seated and after they had been standing for up to 10 minutes both before the study drug was given and at 2 and 4 hours after study drug. The heart rate was significantly lower at 2 hours after pyridostigmine than after placebo (100±16 versus 111±14 bpm, P=0.001). Pyridostigmine significantly decreased the standing heart rate from baseline (119±16 bpm) at 2 hours (104±16 bpm, P<0.001) and 4 hours (100±16 bpm, P<0.001) after administration. There was no significant change in blood pressure. The decrease in symptom burden within 4 hours after study drug was significantly greater with pyridostigmine than placebo (-10.4±14.0 AU versus 0.6±7.5 AU, P<0.025).

Conclusions--Acute acetylcholinesterase inhibition significantly attenuated tachycardia in POTS. There was also an improvement in symptom burden with this promising therapy.

Key words: tachycardia • acetylcholine • nervous system, autonomic • drugs • patients

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