title: Acute nitric oxide synthase inhibition and cardiac conduction in persons with spinal cord injury: a short report.
abstract: NG-nitro L-arginine methyl ester (L-NAME) is a potent and non-specific inhibitor of nitric oxide synthase (NOS). NOS inhibition with L-NAME has been shown to adversely prolong electrocardiogram (ECG) intervals in an animal model, an observation which has yet to be evaluated in humans. We determined the effects of several weight-based L-NAME doses on ECG intervals in persons with tetraplegia and a neurologically-intact control group. This two-part investigation determined the effects of different weight-based doses of L-NAME in the supine (Study 1) and orthostatic position (Study 2). Subjects completed an open-label trial with intravenous administration of L-NAME at specific doses [i.e., 0, 1, 2 or 4 mg.kg-1] in the supine position. The SCI group completed an orthostatic challenge with or without il-NAME [i.e., 0, 1 or 2 mg.kg-'] and controls completed only a single visit [0 mg.kg-1]. Digital ECGs were obtained at baseline (BL), after infusion (60 minutes) and 1 hour post-infusion (120 minutes) in Study 1, and at BL, 60 minutes and at two, 10 minute post-infusion time points after head up tilt (Post-Tilt 1 and 2) in Study 2. Heart rate, PQ, QT, and heart rate corrected QT (QTC) intervals were determined. The groups were matched for demographics. Seven subjects with tetraplegia and 6 controls participated in Study 1; 7 subjects with tetraplegia and 7 controls participated in Study 2. No statistical differences were noted between or within groups at baseline on each study visit for the ECG variables. L-NAME, regardless of dose, did not significantly change any ECG interval. NOS inhibition with L-NAME, at the weight-based doses tested do not induce hypertensive crises and, did not adversely affect any ECG interval in persons with SCI or neurologically intact control subjects during supine rest or orthostatic provocation.
authors.affiliation: VA RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY 10468, USA. michael.lafountaine@va.gov
authors.forename: M F
authors.initials: MF
authors.lastname: La Fountaine
authors.forename: J M
authors.initials: JM
authors.lastname: Wecht
authors.forename: W A
authors.initials: WA
authors.lastname: Bauman
mesh_terms: D000368:Aged; D062186:Arterial Pressure / Q000187:drug effects; D015331:Cohort Studies; D004244:Dizziness; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011782:Quadriplegia / Q000201:enzymology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000201:enzymology*; D016683:Supine Position; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester