Protection against programmed electrical stimulation-induced ventricular tachycardia and sudden cardiac death by NE-10064, a class III antiarrhythmic drug.

Abstract

The electrophysiologic and antifibrillatory properties of NE-10064 were studied in vivo in a conscious canine model of sudden cardiac death. Purpose bred male mongrel dogs weighing 14.5-21.5 kg were anesthetized, and surgical anterior myocardial infarction (MI) was induced by a 2-h occlusion, with reperfusion, of the left anterior descending coronary artery (LAD). Three to 5 days after induction of anterior wall MI, animals were subjected to testing by programmed electrical stimulation (PES). As compared with predrug incidence (12 of 12), NE-10064 (10 mg/kg intravenously, i.v.) reduced (p < 0.05) the incidence (8 of 12) of PES-induced ventricular tachycardia (VT). All but 1 control animal remained inducible after vehicle (5% dextrose in water). The cycle length of induced VT was not prolonged by NE-10064 (0.245 +/- 0.046 s predrug vs. 0.301 +/- 0.060 s postdrug). NE-10064 increased ventricular effective refractory period (VERP 166 +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p = 0.045). The drug did not affect ECG-indexes of conduction velocity: QRS and P-R intervals were not affected, nor were activation delay and conduction time of noninfarcted and infarcted myocardium. In the sudden cardiac death protocol, NE-10064 protected (p = 0.018) against ischemia-induced ventricular fibrillation (VF, 75% survival with drug vs. 25% survival without drug). NE-10064 afforded protection (p = 0.040) throughout 14 h posterolateral ischemia in the presence of the previous anterior infarct.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: S C Black, J L Butterfield, B R Lucchesi
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 22 Issue 6 Pg. 810-8 (Dec 1993) ISSN: 0160-2446 [Print] United States
• PMID: 7509898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Arrhythmia Agents
• Hydantoins
• Imidazoles
• Imidazolidines
• Piperazines
• Piperidines
• azimilide

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology, therapeutic use, toxicity)
• Death, Sudden, Cardiac (etiology, prevention & control)
• Disease Models, Animal
• Dogs
• Electric Stimulation
• Electrocardiography (drug effects)
• Electrophysiology
• Heart Rate (drug effects)
• Hydantoins
• Imidazoles (pharmacology, therapeutic use, toxicity)
• Imidazolidines
• Male
• Myocardial Infarction (complications, physiopathology)
• Piperazines
• Piperidines (pharmacology, therapeutic use, toxicity)
• Tachycardia, Ventricular (etiology, prevention & control)
• Ventricular Fibrillation (prevention & control)