Autonomic ganglionic blockade does not prevent reduction in cerebral blood flow velocity during orthostasis in humans

The underlying mechanisms for reductions in cerebral blood flow (CBF) during orthostasis are not completely understood. This study tested the hypothesis that sympathetic activation causes cerebral vasoconstriction leading to reductions in CBF during lower body negative pressure (LBNP).

CBF velocity, arterial pressure, and end-tidal CO(2) were measured during LBNP (-30 to -50 mm Hg) in 11 healthy subjects before and after autonomic ganglionic blockade with trimethaphan. Arterial partial pressure of CO(2) also was measured in a subgroup of 5 subjects. Mean arterial pressure during LBNP after blockade was maintained by infusion of phenylephrine.

Before blockade, mean arterial pressure did not change during LBNP. However, CBF velocity was reduced in all subjects by 14% (P<0.05). Systolic and pulsatile (systolic-diastolic) CBF velocity were reduced by 18% and 28%, respectively, associated with significant reductions in pulse arterial pressure and end-tidal CO(2) (all P<0.05). After blockade, mean arterial pressure during LBNP was well-maintained and even increased slightly with infusion of phenylephrine. However, reductions in mean, systolic, and pulsatile CBF velocity, pulse arterial pressure, and ETCO(2) were similar to those before blockade. In contrast to reductions in end-tidal CO(2), arterial partial pressure of CO(2) did not change during LBNP.

These data, contrary to our hypothesis, demonstrate that sympathetic vasoconstriction is not the primary mechanism underlying reductions in CBF during moderate LBNP. We speculate that diminished pulse arterial pressure or pulsatile blood flow may reduce cerebral vessel wall shear stress and contribute to reductions in CBF during orthostasis through flow mediated regulatory mechanisms.