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

Abstract

[Figure: see text].

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

Figure 1.

It shows an idealized cardiovagal baroreflex as a sigmoidal relationship between systolic arterial pressure (SAP) and RR interval over a wide range of pressures. The sigmoid curve can be uniquely specified by 4 parameters: the systolic blood pressure (BP; SAP) at the centering point, the slope at the centering point (maximum gain or baroreflex sensitivity, G_max), the curve’s threshold, and its response range. Operating points define the current state of the system; local slopes at operating points and correspond to the variation of RR interval with variation of BP (BPV) near 0.1 Hz near that particular operating point.

Figure 2.

It shows the flow sheet and design of the described studies. The experimental protocol is shown on top and the administration of drugs is shown on the bottom.

Figure 3.

It compares untreated patients with postural tachycardia syndrome (POTS; red lines) with control (black lines) supine and during head-up tilt (HUT). Operating points are shown by red and black circles. G_max and the response range remained unchanged with tilt in control but were reduced in POTS, and further reduced in POTS when tilted. Additional key features of POTS include left lateral and downwards shifts of centering points and operating points and decreased response range with tilt.

Figure 4.

It compares patients with postural tachycardia syndrome (POTS) treated with pyridostigmine (blue lines) with control (black lines) supine and during head-up tilt (HUT). Operating points are shown by blue and black circles. G_max is restored to near control values supine and upright. Supine systolic arterial pressure (SAP) at centering and operating points are similar to control, but threshold is displaced downwards and response range is curtailed. During tilt centering point, SAP and G_max were sustained but response range was greatly reduced during tilt contributing to the left shift of the operating point.

Figure 5.

It compares patients with postural tachycardia syndrome (POTS) treated with digoxin (teal lines) with control (black lines) supine and during head-up tilt (HUT). Operating points are shown by cyan and black circles. Digoxin returns the centering point and G_max of patients with POTS to similar to control values. The response range supine postdigoxin is greater in treated POTS than control. After tilt, threshold was more in POTS while systolic arterial pressure (SAP) at centering point and Gmax were sustained. However, response range decreased markedly with tilt in POTS and contributed to the left shift of the operating point for digoxin and consequently reduced operating point slope.