The effect of bidisomide (SC-40230), a new class Ia/Ib antiarrhythmic agent, on defibrillation energy requirements in dogs with healed myocardial infarctions.
Bidisomide is a Class Ia/Ib antiarrhythmic agent with activity against ventricular and supraventricular arrhythmias. The potential for bidisomide to increase defibrillation threshold (DFT) was tested in anesthetized dogs with healed left ventricular infarcts (> or = 10 days). Defibrillation patches were attached to each ventricle and shocks were delivered via an external cardioverter/defibrillator. Three groups were studied: placebo (saline), canine therapeutic bidisomide (TB, 2-5 micrograms/mL plasma concentration) and supratherapeutic bidisomide (STB, 6-14 micrograms/mL). Each animal received only one treatment. An abbreviated DFT curve was determined before and after treatment. Heart rate, blood pressure, PR, QRS, infarct size, and hematocrit were also measured before and after treatment. DFT was significantly increased (average +3 to +5 joules [J], P < 0.05) by TB and STB. TB (5/5) did not increase DFT beyond 40 J. In 6/7 experiments, STB did not increase DFT beyond 40 J. Placebo (n = 6) had no significant effect on DFT. Infarct size (mean = 11% of the left ventricle) was not significantly different between groups. Heart rate and QRS were not significantly altered but blood pressure was significantly decreased (16%-31% systolic, 29%-45% diastolic) and hematocrit was significantly increased (19% to 25%) in all groups. PR was significantly increased by STB only.


CONCLUSIONS
therapeutic and supratherapeutic doses of bidisomide slightly but significantly increased DFT (3-5 J) in a canine infarcted heart model.
Hackett
A M
AM
Department of Clinical Research, Searle Research and Development, Skokie, Illinois 60077.
Gardiner
P
P
Garthwaite
S M
SM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004554:Electric Countershock; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications*; D010880:Piperidines / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide