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.
CONCLUSION: