Efficacy of pentamidine analogue 6 in dogs with chronic atrial fibrillation

J Vet Intern Med. 2018 Sep;32(5):1549-1554. doi: 10.1111/jvim.15242. Epub 2018 Aug 5.

Abstract

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.

Keywords: adverse effects; arrhythmia; inward rectifier current; plasma; respiratory distress; stridor.

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / veterinary*
  • Dog Diseases / drug therapy*
  • Dogs
  • Female
  • Male
  • Pentamidine / administration & dosage
  • Pentamidine / analogs & derivatives*
  • Pentamidine / therapeutic use*

Substances

  • Anti-Arrhythmia Agents
  • Pentamidine