EFFECTS OF VOLUME LOADING AND PRESSOR AGENTS IN IDIOPATHIC ORTHOSTATIC TACHYCARDIA

Background Idiopathic orthostatic tachycardia (IOT) is characterized b y an increase in heart rate (HR) with standing of greater than or equa l to 30 bpm that is associated with elevated catecholamine levels and orthostatic symptoms. A dynamic orthostatic hypovolemia and alpha(1)-a drenoreceptor hypersensitivity have been demonstrated in IOT patients. There is evidence of an autonomic neuropathy affecting the lower-extr emity blood vessels. Methods and Results We studied the effects of pla cebo, the alpha(1)-adrenoreceptor agonist midodrine (5 to 10 mg), the alpha(2)-adrenoreceptor agonist clonidine (0.1 mg), and IV saline (1 L ) in 13 patients with IOT. Supine and upright blood pressure (BP) and HR were measured before and at 1 and 2 hours after intervention. Midod rine decreased both supine and upright HR (all HR values are given as bpm) at 2 hours (from 78+/-2 supine to 108+/-5 upright before treatmen t and from 69+/-2 supine to 95+/-5 upright after treatment, P<.005 for supine and P<.01 for upright). Saline decreased both supine and uprig ht HR (from 80+/-3 supine to 112+/-5 upright before infusion and from 77+/-3 supine to 91+/-3 upright 1 hour after infusion, P<.005 for supi ne and P<.001 for upright). Clonidine decreased supine HR (from 78+/-2 to 74+/-2, P<.03) but did not affect the HR increase with standing. C lonidine very significantly decreased supine systolic BP (from 109+/-3 at baseline to 99+/-2 mm Hg at 2 hours, P<.001), and midodrine decrea sed supine systolic BP mildly. Conclusions IOT responds best acutely t o saline infusion to correct the underlying hypovolemia. Chronically, this can be accomplished with increased salt and water intake in conju nction with fludrocortisone. The response of patients to the alpha(1)- agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of alpha(1)-agonists to pharmacologically repla ce lower-extremity postganglionic sympathetics is an appropriate overa ll goal of therapy; These findings are consistent with our hypothesis that the tachycardia and elevated catecholamine levels associated with IOT are principally due to hypovolemia and loss of adequate lower-ext remity vascular tone.