The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs.
Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens.


CONCLUSIONS
Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.
Kulier
A H
AH
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
Novalija
E
E
Hogan
Q
Q
Vicenzi
M N
MN
Woehlck
H J
HJ
Bajic
J
J
Atlee
J L
JL
Bosnjak
Z J
ZJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001572:Benzofurans / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels / Q000601:surgery; D004285:Dogs; D005079:Excipients / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008026:Ligation; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications* / Q000209:etiology; D010865:Pilot Projects; D011136:Polysorbates / Q000008:administration & dosage
C402242:((2-butyl-3-benzofuranyl)-(5-(2-diethylamino)ethoxy)-2-thienyl)methanone; D000889:Anti-Arrhythmia Agents; D001572:Benzofurans; D005079:Excipients; D011136:Polysorbates