Raised Cerebrovascular Resistance in Idiopathic Orthostatic Intolerance

Abstract

Abstract-Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and ␣-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by ␣-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (Ϫ20Ϯ3.2 bpm) and phenylephrine (Ϫ18Ϯ3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20Ϯ3.7 bpm) and at the end of HUT (14Ϯ5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33Ϯ6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, ␣-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture. (Hypertension. 1998;32:699-704.)Key Words: cerebral blood flow Ⅲ receptors, adrenergic Ⅲ phentolamine Ⅲ phenylephrine Ⅲ intolerance, orthostatic Ⅲ tachycardia I diopathic orthostatic intolerance (IOI) is commonly defined as a Ͼ30 bpm increase in heart rate (HR) with standing associated with orthostatic symptoms but without significant orthostatic hypotension.1 The pathophysiology of this disorder, which mainly affects women in the second or third decade of life, is still imperfectly understood.2 It has been suggested that hypovolemia, 3,4 excessive venous pooling in the lower extremities, 5 partial dysautonomia involving the vasculature of the legs, 6-8 or hypersensitivity of ␤-adrenoreceptors 9,10 can contribute to the hemodynamic abnormalities of IOI. The unifying feature of patients with IOI is the presence of symptoms suggestive of cerebral hypoperfusion (eg, presyncope, visual changes, altered mentation) associated with standing despite largely sustained systemic arterial pressure. Recently, an excessive decrease in cerebral blood flow velocity with upright posture as well as stable mean arterial pressure (MAP) was reported in a single patient with a history and physical findings suggestive of IOI.11 Similarly, in a larger group of well-characterized IOI patients, mean middle cerebral blood flow velocity (mean MCA vel ) decreased by 28% with 75°HUT; age-and gender-mat...

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