Clinical and Physiological Effects of an Acute α-1 Adrenergic Agonist and a β-1 Adrenergic Antagonist in Chronic Orthostatic Intolerance

Abstract

Background— Adrenergic agents are commonly used in the treatment of chronic orthostatic intolerance with postural tachycardia syndrome (POTS). POTS may be associated with increased limb blood flow (“high flow”) and defective orthostatic vasoconstriction or decreased limb blood flow (“low flow”) and potentially with small blood volume. Methods and Results— We investigated the consequences of short-term intravenous administration of an α-1 adrenergic agonist, phenylephrine, and a β-1 adrenergic antagonist, esmolol, in 14 patients with POTS aged 13 to 19 years. Indices of heart rate and blood pressure variability, peripheral blood flow, and arterial resistance were assessed, and the capacitance relation was computed for every subject using venous occlusion plethysmography. Patients were tilted to 35° upright while medicated and while unmedicated, and measurements were repeated. Phenylephrine improved orthostatic tolerance and normalized hemodynamics and indices of heart rate/blood pressure variability while supine and while upright, producing significant peripheral vasoconstriction and venoconstriction (20% capacitance change). Esmolol did not improve orthostatic tolerance or hemodynamics. A subgroup of low-flow POTS patients had exaggerated venoconstriction to phenylephrine (50% capacitance change) but others had no response. Conclusions— Phenylephrine, but not esmolol, improves orthostatic tolerance and hemodynamics in POTS. This lends support to the use of oral α-1 agonists in the treatment of patients with chronic orthostatic intolerance.

Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome

“…However, administration of nonselective vasoconstrictive agents may cause a simple reduction of cerebral blood flow via elevation of cerebrovascular resistance, although intravenous infusion of phenylephrine, a sympathetic nerve α 1 stimulator, has been reported to improve OI, as a result of producing significant peripheral vasoconstriction and venoconstriction in some OI patients. 31 Volume repletion by increasing sodium intake or by treatment with fludrocortisones may theoretically improve OI and also symptoms of CFS by replenishing intravascular volume. 4,7,9,22,25 Military antishock trousers and elastic stockings may also be effective via potentiation of venous return, resulting in increased cardiac output.…”

Midodrine Hydrochloride Is Effective in the Treatment of Children With Postural Orthostatic Tachycardia Syndrome

“…13 But in 2002, Stewart et al reported that esmolol could not improve OI and hemodynamics in POTS. 4 Up to now, there are disputations on the effect of β-blockers for POTS.…”

“…Treatment of POTS most often involves pharmacotherapy, commonly with β-blockers; however, there are disputations on the effect of β-blockers for POTS. In 2002, Stewart et al 4 reported that esmolol could not improve orthostatic tolerance and hemodynamics in POTS. Midodrine hydrochloride, a selective α-agonist, is particularly attractive because it significantly decreases venous capacitance and might be effective at doses that do not increase blood pressure.…”

Small Heart as a Constitutive Factor Predisposing to Chronic Fatigue Syndrome

“…However, administration of nonselective vasoconstrictive agents may cause a simple reduction of cerebral blood flow via elevation of cerebrovascular resistance, although intravenous infusion of phenylephrine, a sympathetic nerve α 1 stimulator, has been reported to improve OI, as a result of producing significant peripheral vasoconstriction and venoconstriction in some OI patients. 56 Volume repletion by increasing sodium intake or by treatment with fludrocortisones may theoretically improve OI and also symptoms of CFS by replenishing intravascular volume. 17,35,38,42,46 Military anti-shock trousers as well as elastic stockings which compress lower extremities may also be effective via potentiation of venous return, resulting in increased cardiac output.…”