Efficacy of pentamidine analogue 6 in dogs with chronic atrial fibrillation

Background: The inward rectifier inhibitor pentamidine analogue 6 (PA-6) is effective in cardioversion of goats with persistent rapid pacing induced atrial fibrillation (AF) and is not proarrhythmic in dogs with experimental chronic 3rd-degree AV block. Efficacy and safety in the clinical setting are unknown. Hypothesis: That PA-6 would be effective in converting AF to sinus rhythm (SR) in dogs with naturally occurring AF, without the presence of overt adverse effects. Animals: Ten client-owned large and giant breed dogs. Methods: Animals with persistent or permanent AF were recruited for our prospective study. PA-6 was administered IV as a bolus of 2.5 mg/kg 10 min⁻¹ followed by a maintenance infusion of 0.04 mg/kg min⁻¹ for a maximum of 50 minutes in conscious dogs. Standard 6 lead limb ECG was recorded during the infusion. Visible and audible signs of adverse effects were scored during the entire procedure. Results: PA-6 did not induce changes in QRS duration (54.7 ± 4.6 versus 56.7 ± 6.1 ms, P =.42), QTc interval (241.1 ± 19.5 versus 258.7 ± 19.8 ms, P =.061) or RR interval (363.4 ± 84.6 versus 440.8 ± 96.3 ms, P =.072) at the end of the bolus. No cardioversion to SR was observed in any dog. Three dogs displayed no adverse effects. Five dogs had premature ventricular depolarizations during PA-6 infusion on the ECG. Respiratory distress with laryngeal stridor, subtle muscle twitching, and mild generalized muscular weakness were noncardiac adverse effects observed in 5 dogs. Adverse effects resolved spontaneously. Conclusions and Clinical importance: Chronic naturally occurring AF in large and giant breed dogs could not be cardioverted to SR by PA-6.