Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls

Jill M Wecht, Joseph P Weir, Miroslav Radulovic, William A Bauman, Jill M Wecht, Joseph P Weir, Miroslav Radulovic, William A Bauman

Abstract

We previously showed that increases in mean arterial pressure (MAP) following administration of midodrine hydrochloride (MH) and nitro-L-arginine methyl ester (L-NAME) resulted in increased mean cerebral blood flow velocity (MFV) during head-up tilt in hypotensive individuals with spinal cord injury (SCI) and question if this same association was evident during cognitive activation. Herein, we report MAP and MFV during two serial subtraction tasks (SSt) given before (predrug) and after (postdrug) administration of MH; (10 mg), L-NAME (1 mg/kg) or no drug (ND) in 15 subjects with SCI compared to nine able-bodied (AB) controls. Three-way factorial analysis of variance (ANOVA) models were used to determine significant main and interaction effects for group (SCI, AB), visit (MH, L-NAME, ND), and time (predrug, postdrug) for MAP and MFV during the two SSt. The three-way interaction was significant for MAP (F = 4.262; P = 0.020); both MH (30 ± 26 mmHg; P < 0.05) and L-NAME (27 ± 22 mmHg; P < 0.01) significantly increased MAP in the SCI group, but not in the AB group. There was a significant visit by time interaction for MFV suggesting an increase from predrug to postdrug following L-NAME (6 ± 8 cm/sec; P < 0.05) and MH (4 ± 7 cm/sec; P < 0.05), regardless of study group, with little change following ND (3 ± 3 cm/sec). The relationship between change in MAP and MFV was significant in the SCI group following administration of MH (r(2) = 0.38; P < 0.05) and L-NAME (r(2) = 0.32; P < 0.05). These antihypotensive agents, at the doses tested, raised MAP, which was associated with an increase MFV during cognitive activation in hypotensive subjects with SCI.

Keywords: Blood pressure; L‐NAME; Midodrine; NOS inhibition; cerebral blood flow; cognition; spinal cord injury; tetraplegia.

© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Figures

Figure 1
Figure 1
Change from predrug to postdrug following L‐NAME (open triangles), MH (closed squares) and ND (open circles) for MAP (top panels), SBP (middle panels), and DBP (bottom panels) in the SCI (A, C, E) and AB (B, D, F) groups.
Figure 2
Figure 2
Change from predrug to postdrug following L‐NAME (open triangles), MH (closed squares) and ND (open circles) for MFV (top panels), SFV (middle panels), and DFV (bottom panels) in the SCI (A, C, E) and AB (B, D, F) groups.
Figure 3
Figure 3
Relationship between change in MAP and change in MFV from predrug to postdrug during the SSt following MH (closed circles) and LN (open squares) in the SCI group. The slope of this relationship was significant for MH (r2 = 0.39; P < 0.01) and LN (r2 = 0.33; P < 0.05).

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