EXCESSIVE GRAVITATIONAL BLOOD POOLING CAUSED BY IMPAIRED VENOUS TONE IS THE PREDOMINANT NONCARDIAC MECHANISM OF ORTHOSTATIC INTOLERANCE

1. In a group of 40 patients with orthostatic intolerance due to hypot ension and/or tachycardia, we have compared the pathogenetic roles of impaired contractility of the arterioles and the veins by measuring co ntractile responsiveness of the arterioles, reflected by increases in diastolic blood pressure and of the veins reflected by measurements of reduction in venous diameter during intravenous noradrenaline infusio ns, 2. Compared with 27 healthy subjects, patients with diffuse autono mic insufficiency showed striking supersensitivity in diastolic blood pressure (six out of eight) and venous constrictive responses (seven o ut of eight patients) to noradrenaline, consistent with impaired arter iolar and venous innervation, 3. In contrast, the patients with hypera drenergic orthostatic hypotension (n=16) and orthostatic tachycardia ( n=16) showed diastolic blood pressure responses to noradrenaline that were almost invariably within the 95% confidence limits of the changes in normal subjects but supersensitive constrictive responses of foot veins in 22 of 32 subjects and subnormal venous responses in two indiv iduals, The rate of noradrenaline infusion calculated to cause 50% of maximal venous constriction (the ED(50)) was significantly lower in th e patients [mean (SEM) 6.8 (1.9) ng/min] than in the normal subjects [ mean (SEM) 23.2 (3.0) ng/min, P<0.025]. 4. The finding of significantl y supersensitive foot vein constrictive responses to noradrenaline inf usion in the patients of all three groups and supersensitive blood pre ssure responses exclusively in the patients with diffuse autonomic ins ufficiency indicates that venous pooling in the legs was the predomina nt pathogenetic mechanism of orthostatic intolerance in all three type s of patients studied, 5. Correction of the orthostatic hypotension an d/or tachycardia by external compression in virtually all patients con firmed this conclusion.