Effects of azimilide, acidemia, and the combination on defibrillation energy requirements.
We investigated the effects of azimilide, acidemia, and the combination on the defibrillation energy requirement (DER). An anesthetized canine model of internal transvenous defibrillation with biphasic shocks was used. Dogs were assigned to receive a 0.25N HCl infusion (target pH, 7.15), azimilide, azimilide with HCl infusion, or placebo (n = 7 per treatment). DERs were determined in triplicate using an increment-decrement protocol at baseline and during each treatment. Monophasic action potentials and ECG intervals were measured at baseline and during each treatment. Analysis of variance (ANOVA) with post hoc Tukey's test was used for statistical analysis. The DER was reduced by azimilide and increased above control values by both acidemia and the combination of acidemia and azimilide. All treatment groups resulted in a significant change compared with placebo (p < 0.05). The correlation between DER and various repolarization measurements was determined. The treatment-related changes in both QT intervals and monophasic action potential (MAP) durations were inversely correlated with DER. Azimilide reduces the DER, whereas acidemia increases the DER in our model. The combination of azimilide and acidemia still resulted in an increase in the DER. This finding may have clinical implications for the use of azimilide in settings such as myocardial ischemia, in which myocardial pH is reduced.
Carnes
C A
CA
The Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Mehdirad
A A
AA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004554:Electric Countershock; D004562:Electrocardiography; D005260:Female; D006827:Hydantoins; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D010879:Piperazines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; C086123:azimilide; D006851:Hydrochloric Acid