Abstract 816: Sympathetic Nerve Protein Analysis, Sympathetic Microneurography and Catecholamine Kinetics in Postural Syncope Phenotypes
Background: Vasovagal syncope (VVS), postural tachycardia syndrome (POTS), and low supine systolic blood pressure (LSBP) are common causes of postural syncope. The sympathetic nervous system is critical to neurocirculatory control. POTS is characterized by a hyperadrenergic state which we hypothesize is due to norepinephrine transporter (NET) dysfunction. In contrast, LSBP may be secondary to low sympathetic activity. VVS, it is claimed, is characterized by sympathetic withdrawal (cessation of MSNA- muscle sympathetic nerve activity) and an epinephrine surge during the faint.
Methods: We performed HUT (head-up tilt) with whole body norepinephrine (NE) kinetics and MSNA (microneurography) in untreated patients with POTS (n = 14), VVS (n = 10), and LSBP (n = 10). A subset of patients underwent subcutaneous forearm vein biopsy, to examine sympathetic nerve proteins by Western blot (NET and tyrosine hydroxylase, TH).
Results: LSBP group was characterized by low NE spillover and MSNA at rest compared to the control group (p<0.05). POTS subjects had normal NE spillover and MSNA, but during HUT they displayed excessive MSNA response and normal NE spillover suggesting electro-chemical dysjunction in sympathetic nerves. Protein extraction from vein biopsies showed that POTS patients had minimal/absent NET protein. LSBP patients have low TH which may explain low blood pressure and the tendency to faint. Preliminary data reveal increased NET protein in VVS, and contrary to current belief we found no evidence of sympathetic withdrawal, as defined by cessation of MSNA.
Conclusions: LSBP is a distinct clinical disorder characterized by low sympathetic tone. The absence of NET in POTS may underlie the hyperadrenergic state; sympathetic nerve protein analysis may be useful in diagnosis. Sympathetic withdrawal does not occur in VVS; excess NET may be implicated in pathogenesis and our findings provide a scientific rationale for therapeutic use of Reboxetine (NET inhibitor).