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

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.