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Effects of 4‐Aminopyridine on Cardiac Repolarization, PR Interval, and Heart Rate in Patients with Spinal Cord Injury
Author(s) -
Isoda Wakana C.,
Segal Jack L.
Publication year - 2003
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.23.2.133.32089
Subject(s) - medicine , qt interval , heart rate , anesthesia , tetraplegia , cardiology , 4 aminopyridine , spinal cord injury , electrocardiography , blood pressure , spinal cord , potassium channel , psychiatry
Study 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). Design . Randomized, active‐treatment—controlled, dose level—blinded study with allocation concealed. Setting . University‐affiliated, tertiary care medical center. Patients . 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. Measurements and Main 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. Conclusion . 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.