title: 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.
authors: VA RR&D National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VAMC, Bronx, New York The Medical Service, James J. Peters VAMC, Bronx New York Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York jm.wecht@va.gov.
authors: Jill M
authors: JM
authors: Wecht
authors: Department of Health, Sport and Exercise Sciences, The University of Kansas, Lawrence, Kansas.
authors: Joseph P
authors: JP
authors: Weir
authors: VA RR&D National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VAMC, Bronx, New York The Medical Service, James J. Peters VAMC, Bronx New York Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors: Miroslav
authors: M
authors: Radulovic
authors: VA RR&D National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters VAMC, Bronx, New York The Medical Service, James J. Peters VAMC, Bronx New York Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors: William A
authors: WA
authors: Bauman
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008879:Midodrine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D014662:Vasoconstrictor Agents; D008879:Midodrine; D019331:NG-Nitroarginine Methyl Ester
keywords: Blood pressure; L‐NAME; Midodrine; NOS inhibition; cerebral blood flow; cognition; spinal cord injury; tetraplegia