Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride

Abstract

Individuals with high-level spinal cord injury (SCI) experience low blood pressure (BP) and cognitive impairments. Such dysfunction may be mediated in part by impaired neurovascular coupling (NVC) (i.e., cerebral blood flow responses to neurologic demand). Ten individuals with SCI >T6 spinal segment, and 10 age- and sex-matched controls were assessed for beat-by-beat BP, as well as middle and posterior cerebral artery blood flow velocity (MCAv, PCAv) in response to a NVC test. Tests were repeated in SCI after 10 mg midodrine (alpha1-agonist). Verbal fluency was measured before and after midodrine in SCI, and in the control group as an index of cognitive function. At rest, mean BP was lower in SCI (70 ± 10 versus 92 ± 14 mm Hg; P<0.05); however, PCAv conductance was higher (0.56 ± 0.13 versus 0.39 ± 0.15 cm/second/mm Hg; P<0.05). Controls exhibited a 20% increase in PCAv during cognition; however, the response in SCI was completely absent (P<0.01). When BP was increased with midodrine, NVC was improved 70% in SCI, which was reflected by a 13% improved cognitive function (P<0.05). Improvements in BP were related to improved cognitive function in those with SCI (r(2)=0.52; P<0.05). Impaired NVC, secondary to low BP, may partially mediate reduced cognitive function in individuals with high-level SCI.

Figures

Figure 1

Cerebrovascular response to visual–spatial task. Mean arterial pressure (MAP), posterior cerebral artery (PCA) mean flow velocity (vmean), cerebrovascular conductance (CVC), and partial pressure end-tidal carbon dioxide (PETCO2) response during verbal fluency testing. Gray line represents able-bodied individuals, black dashed line represents spinal cord injury (SCI) before midodrine, thick black line represents spinal cord injury after midodrine (SCImido). The black filled rectangle represents the 30-second activation period, whereas the six smaller empty rectangles represent 5-second bins from the activation period. Mean arterial pressure and PETCO2 did not change significantly in response to the visual task. Posterior cerebral artery mean flow velocity and PCAcvc did not significantly increase in SCI. Posterior cerebral artery mean flow velocity and PCAcvc increased significantly during activation in SCI after midodrine; however, this response was still reduced as compared with the significant response in AB. AB, able-bodied control; CBF, cerebral blood flow.

Figure 2

Cerebrovascular response to verbal fluency task. Mean arterial pressure (MAP), middle cerebral artery (MCA), mean flow velocity, cerebrovascular conductance (CVC), and partial pressure end-tidal carbon dioxide (PETCO2) response during verbal fluency testing. Gray line represents able-bodied individuals, black dashed line represents spinal cord injury (SCI) before midodrine, thick black line represents spinal cord injury after midodrine (SCImido). The black filled rectangle represents the 30-second activation period, whereas the six smaller empty rectangles represent 5-second bins from the activation period. Although MCAv, MCAcvc, and PETCO2 significantly changes during the activation period, there were no significant differences between AB, SCI, or SCImido with respect to their responses. AB, able-bodied controls; CBF, cerebral blood flow.

Figure 3

The relationship between changes systemic and cerebral parameters and changes in verbal fluency (VF) scores in those with spinal cord injury (SCI). Individuals with larger increases in mean arterial pressure (MAP) also had larger increases in VF. Also, those with greater reductions in resting conductance in the middle cerebral artery (MCAcvc) had larger increases in VF. Symbols represent individual participants.