1. Studies were carried out on 43 otherwise healthy patients referred for investigation for attacks of syncope of unknown cause and on six healthy volunteers.
2. Plasma volume was determined by Evans Blue dye dilution and blood volume was estimated using haematocrit. Carotid baroreceptor sensitivity was determined from the changes in pulse interval in response to subatmospheric pressures applied to the neck overlying the carotid sinuses, and orthostatic tolerance was assessed as the time to presyncope in a test of head-up tilt, followed by the addition of graded lower body suction.
3. Eight patients and one volunteer fainted during head-up tilt alone, 23 patients and two volunteers fainted during tilt with lower body suction at −20 mmHg and 12 patients and three volunteers either fainted during suction at −40 mmHg or tolerated the entire procedure.
4. Although plasma and blood volumes were higher in males than females, the values normalized for either body weight or for calculated lean body mass were not different between male and female patients and asymptomatic volunteers. The subjects showing the greatest resistance to syncope were found to have significantly larger plasma and blood volumes (P < 0.0001) and significantly smaller baroreceptor sensitivities (P < 0.0002) than those who fainted earlier.
5. There was a highly significant positive correlation in all subjects between orthostatic tolerance (time to onset of syncope) and plasma and blood volumes (r = 0.60, P < 0.0001; r = 0.53, P < 0.0002), and highly significant negative correlations between time to syncope and baroreceptor sensitivity (r = −0.61, P < 0.0001) and between baroreceptor sensitivity and plasma and blood volumes (r = −0.54, P < 0.0001; r = −0.31, P < 0.03).
6. These results show that tolerance to orthostatic stress is favoured by large plasma and blood volumes and a low sensitivity of the carotid baroreceptor—heart rate reflex.