In multiple system atrophy (MSA), increased venous compliance with excessive venous pooling is assumed to be a major contributor to orthostatic hypotension (OH); however, venous compliance has never been assessed in MSA patients. We evaluated the severity and distribution of adrenergic, cardiovagal, and sudomotor failure in 11 patients with probable MSA, 14 age- and sex-matched control subjects, and 8 patients with Parkinson's disease (PD) but not OH. Calf venous compliance, venous filling, and capillary filtration were measured using calf plethysmography. The response to the directly acting alpha-adrenergic stimulation (10 mg midodrine) on calf venous compliance was additionally evaluated. Contrary to our hypothesis, pressure-volume curves in the legs of MSA patients were flatter than in PD patients (P < 0.05) or controls (P < 0.001); this indicated reduced calf venous compliance in MSA. The MSA group had reduced venous filling compared with control (P < 0.001) or PD subjects (P < 0.001) but had a normal capillary filtration rate (P = 0.73). Direct alpha-adrenergic stimulation resulted in a slight but significant reduction of calf venous compliance in controls (P = 0.001) and PD subjects (P < 0.001) but not in the MSA group. The compliance change in MSA significantly regressed with autonomic failure (composite autonomic severity scale, r(2) = 0.56) but not with parkinsonism (Unified MSA Rating Scale, r(2) = 0.12). Our data indicate that MSA patients with chronic OH have reduced, rather than increased, venous compliance in the lower leg. We postulate that chronic venous distension that is associated with OH results in structural remodeling of veins, leading to reduced compliance, a change which may protect patients against orthostatic stress.
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