Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome: Effects of Pyridostigmine and Digoxin

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Upright postural tachycardia syndrome (POTS) resembles hemorrhage with reduced central blood volume, parasympathetic withdrawal, and sympathetic activation. Baroreflex dysfunction causes low heart rate variability, enhanced blood pressure variability, and decreased maximum baroreflex gain (Gmax) putatively measured by spontaneous fluctuation of blood pressure and heart rate. We investigated whether/how cardiovagal baroreflex in POTS differ from control, supine, and upright by comparing indices of spontaneous baroreflex function to that measured using the reference standard modified Oxford method. This uses sodium nitroprusside and phenylephrine to generate the sigmoidal cardiovagal baroreflex curve. Baroreflex in POTS was evaluated supine and upright untreated and then treated to determine whether pyridostigmine or digoxin (a vagotonic agent) corrects baroreflex deficits. Supine, Gmax was reduced by 25% in POTS compared with controls, and descriptors of this sigmoidal relationship showed a reduction, downward shift, and left shift of the response to the pharmacological decrease and increase in blood pressure. Digoxin normalized supine cardiovagal baroreflex while pyridostigmine resulted in partial normalization as Gmax, and other descriptors of these relationships were similar to control. Upright, cardiovagal curves were distorted and displaced in untreated POTS, while digoxin and pyridostigmine left shifted the cardiovagal curves due to sympathetic activity. Cardiovagal baroreflex deficits in POTS relate to parasympathetic withdrawal while supine, remediated completely by digoxin, and sympathetic activation upright through alteration of baroreflex responsivity. Since these baroreflex effects resemble those measured following microgravity/chronic bedrest, vagotonic/sympatholytic treatment combined with aerobic exercise might normalize the cardiovagal baroreflex and provide therapeutic benefit in patients with POTS.

Keywords: baroreflex; digoxin; modified oxford method; orthostasis; postural tachycardia syndrome; pyridostigmine.