Effects of mexiletine on the canine model of sparfloxacin-induced long QT syndrome.
Potential utility of mexiletine for the treatment of sparfloxacin-induced long QT syndrome was assessed using the in vivo halothane-anesthetized canine model. At 30 min after the administration of a supratherapeutic dose of sparfloxacin (30 mg/kg, i.v.), the mean blood pressure and heart rate decreased, whereas repolarization process and effective refractory period of the ventricular muscle were significantly prolonged. Additional administration of a clinically recommended dose of mexiletine (3 mg/kg, i.v.) at this time point increased the mean blood pressure, suppressed ventricular contraction, delayed atrioventricular as well as intraventricular conduction, and shortened repolarization process and effective refractory period. The extent of abbreviation of the repolarization was more prominent than that of the refractoriness, indicating that mexiletine could decrease the electrical vulnerability of the heart during sparfloxacin overdose. Thus, mexiletine may become a promising pharmacological strategy against the drug-induced long QT syndrome.
Takahara
Akira
A
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
Sugiyama
Atsushi
A
Satoh
Yoshioki
Y
Hashimoto
Keitaro
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002036:Bundle of His / Q000187:drug effects / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008801:Mexiletine / Q000627:therapeutic use*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D008801:Mexiletine; C061363:sparfloxacin