Comparison of the effects of intravenous LNC-834, a new antiarrhythmic agent, and quinidine in canine models of arrhythmia.

Abstract

The effects of intravenous LNC-834, a new antiarrhythmic agent, and quinidine sulfate were evaluated and compared in 24-h infarction, programmed electrical stimulation (PES), and ventricular fibrillation threshold (VFT) canine models of cardiac arrhythmias. In the 24-h infarction model (24 h after myocardial infarction), animals averaged 85% arrhythmic beats before treatment. LNC-834 gave greater suppression of these spontaneous arrhythmias (97%) and had a longer duration of action (150 min) than did quinidine (70% and 85 min, respectively) at 10 mg of base/kg, although plasma levels were comparable (1.82 +/- 0.19 and 1.50 +/- 0.27 micrograms/ml of plasma for LNC-834 and quinidine, respectively). At 10 mg of base/kg, LNC-834 and quinidine increased effective refractory periods by 9 and 7%, respectively. In the PES model, LNC-834 (3 mg of base/kg) suppressed ventricular tachycardia (VT) in 33% (2/6) of the dogs tested: none of the six quinidine-treated animals displayed suppression of VT at cumulative doses of 0.3 to 30 mg of base/kg. In PES dogs, inducible and noninducible, mortality was less with LNC-834 treatment than with quinidine [9% (1/11) and 36% (4/11), respectively]. Neither LNC-834 nor quinidine elevated VFT in naive, anesthetized dogs. Although no treatment significantly affected the intrinsic heart rate in VFT dogs, both LNC-834 and quinidine produced significant hypotension; however, LNC-834 caused less hypotension than did quinidine at equal doses. This study demonstrates that LNC-834 may be a useful antiarrhythmic agent with efficacy comparable to and hemodynamic advantages over quinidine.

• Authors: A J D'Alonzo, J L Butterfield, A P Drexler, S L Sergio
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 16 Issue 3 Pg. 506-17 (Sep 1990) ISSN: 0160-2446 [Print] United States
• PMID: 1700225 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• 3-hydroxy-10,11-dihydroquinidine
• Quinidine

Topics

• Animals
• Anti-Arrhythmia Agents (administration & dosage, adverse effects, therapeutic use)
• Arrhythmias, Cardiac (drug therapy, physiopathology)
• Disease Models, Animal
• Dogs
• Dose-Response Relationship, Drug
• Electrophysiology
• Female
• Hemodynamics (drug effects)
• Hypotension (chemically induced)
• Male
• Quinidine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Ventricular Fibrillation (drug therapy, physiopathology)