title: Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.
abstract: OBJECTIVE
  To determine the effects of 4-aminopyridine (4-AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI).
  
  
  METHODS
  Randomized, active-treatment-controlled, dose level-blinded study, with allocation concealed.
  
  
  METHODS
  University-affiliated, tertiary care medical center.
  
  
  METHODS
  Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration. Intervention. Oral administration and dose titration to tolerance of an immediate-release formulation of 4-AP.
  
  
  RESULTS
  The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12-lead electrocardiograms (ECGs) at baseline (before administration of 4-AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12-lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4-AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex.
  
  
  CONCLUSIONS
  During the 1-month period that 4-AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature-derived control values. 4-Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life-threatening ventricular dysrrhythmias when administered long-term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4-AP for up to 1 month.
authors.affiliation: Research and Education Institute Summer Research Fellowship Program, Toyota Motor Corporation of America, Torrance, California, USA.
authors.forename: Wakana C
authors.initials: WC
authors.lastname: Isoda
authors.forename: Jack L
authors.initials: JL
authors.lastname: Segal
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010264:Paraplegia; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D011782:Quadriplegia; D013119:Spinal Cord Injuries / Q000473:pathology
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine