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.