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

doi:10.14814/phy2.12683

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; (10mg), L-NAME (1mg/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±26mmHg; P<0.05) and L-NAME (27±22mmHg; 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±8cm/sec; P<0.05) and MH (4±7cm/sec; P<0.05), regardless of study group, with little change following ND (3±3cm/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.

Highlights

Decentralized autonomic cardiovascular control in persons with spinal cord injury (SCI) often results in chronic hypotension and orthostatic hypotension (OH), in individuals with high cord lesions.While most hypotensive individuals with chronic SCI remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion, evidence of reduced resting cerebral blood flow (CBF) has been reported in association with low systemic blood pressure a 2016 The Authors
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
We recently found that middle cerebral artery CBF velocity (CBFv) was not increased during cognitive testing in individuals with SCI (Wecht et al 2012), and noted significantly impaired memory and marginally impaired attention processing in hypotensive individuals with SCI compared to a normotensive SCI cohort (Jegede et al 2010)

Summary

Introduction

While most hypotensive individuals with chronic SCI remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion (i.e., dizziness, lightheadedness, blurry vision, nausea, etc.), evidence of reduced resting cerebral blood flow (CBF) has been reported in association with low systemic blood pressure a 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Given the potential adverse impact of asymptomatic hypotension on CBF and cognitive function in the SCI population treatment options for low BP should be considered. We reported disparity between the evidence of hypotension (%40%) and the clinical diagnosis (

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