The location of the human volume indifferent point predicts orthostatic tolerance

The volume indifferent point (VIP) is the point within the circulation where blood volume does not change with changes in posture. Because both volume and pressure are unaffected by posture at this point, its location should dictate the filling gradient to the heart. Previously we identified a contribution of the splanchnic circulation to its location. We experimentally manipulated blood volume in the splanchnic region to quantify changes in the VIP. Furthermore, we determined the relationship between the VIP and an individual's tolerance to an orthostatic stress. In Protocol 1, we found that administration of the somatostatin analog octreotide acetate, which elicits relatively selective splanchnic vasoconstriction, induced a superior shift in the VIP (+1.9 +/- 3.3 cm, P = 0.03). This finding corroborates previous reports of improvements in tilt tolerance after octreotide and suggests it might be related to relocation of the VIP. In Protocol 2, application of -20 mmHg lower body negative pressure (LBNP) induced splanchnic pooling and moved the VIP inferiorly (-6.0 +/- 7.2 cm, P < 0.01). LBNP combined with head-up tilt significantly decreased tilt tolerance (median tilt time: 28.0 vs. 4.2 min; Chi (2) = 14.29, P < 0.01); the change in the VIP predicted the reduction in tilt time (Deltatilt time = 3.05 + 0.12 DeltaVIP, P = 0.03). Thus, individuals with the largest inferior shift in the VIP also demonstrated the largest decrease in tilt table tolerance. We conclude that the splanchnic circulation plays an important role in determining the location of the VIP and the location of the VIP is a determinant of tolerance to orthostatic stress.