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.

Vascular-Cognitive Impairment following High-Thoracic Spinal Cord Injury Is Associated with Structural and Functional Maladaptations in Cerebrovasculature

“…5 Multiple studies from our group and others have presented a relationship between cerebrovascular dysfunction and cognitive decline in individuals with SCI. [6][7][8] Intriguingly, cerebrovascular function is only partially restored in response to normalization of systemic BP, indicating that other factors, for example, vascular remodeling, fibrosis, and endothelial dysfunction, may contribute to the observed vascular impairment associated with SCI. We have previously used a rat model to demonstrate that high-thoracic SCI leads to significant fibrosis and increased stiffness of the cerebrovasculature at the sub-acute stage.…”

Patterns of cognitive deficits in persons with spinal cord injury as compared with both age-matched and older individuals without spinal cord injury

“…27 Although the etiology of the cognitive deficits in SCI remains elusive, several factors have been suggested as contributory including concomitant traumatic brain injury (TBI), 2,3,10,11,[28][29][30][31][32][33][34] secondary trauma as a result of cerebral edema, hypoxia and anoxia 27 and cardiovascular and cerebrovascular dysfunction. 7,35,36 Recent studies also suggest that factors such as sleep disordered breathing/sleep apnea, 31 core body temperature dysregulation, 37,38 as well as medications prescribed for symptom management such as pain, 39,40 and neurogenic lower urinary tract dysfunction 41 may contribute to post-SCI cognitive dysfunction. Recent work by Bombardier and colleagues 42 highlight the likelihood that factors other than TBI likely contribute to cognitive deficits post-SCI, because the number of patients reporting cognitive deficits exceeded physician-rated presence of TBI by 80% in their sample of 105 persons with SCI.…”

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

“…As a common motor system trauma in the clinic, SCI has been observed to induce various degrees of extremity swelling or paraplegia and loss of ability to work, bringing a tremendous burden on society and the patient's family (1). The epidemiological data in American regions demonstrate that traffic accidents and high-altitude falls are the major causes of injury, with cases more often occurring in young men, with an average age of 30 years old.…”