Electrophysiologic, haemodynamic and antiarrhythmic effects of the new class Ic agent 1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride.
The electrophysiological, antiarrhythmic and haemodynamic profile of the new compound GK 23-G (1-(2'-biphenyloxy)-2-tert.-butylamino-propanol-2-hydrochloride, proposed INN: bipranol) was examined using dogs models relevant to conditions in humans. In the first part of the study, dose-related effects of cumulatively increasing doses of GK 23-G (0.2-12.8 mg/kg) on intracardiac conduction, ventricular refractoriness and on haemodynamic parameters of the non-ischemic heart were determined in six anesthetized mongrel dogs. In the second part of the study, antiarrhythmic actions of bipranol on "delayed reperfusion ventricular arrhythmias" following release of coronary artery occlusion after 2 h of obstruction were investigated in another six dogs. The results show: GK 23-G causes a significant prolongation of HV-time, QRS-duration and ventricular refractory period at mid-range and high doses (greater than or equal to 3.2 mg/kg). QT-time does not change. Atrial refractory period is significantly lengthened at the maximum dose of 12.8 mg/kg. There are no significant changes in heart rate, systolic and diastolic aortic pressure and cardiac output. Up to 12.8 mg/kg, GK 23-G does not influence left ventricular contractility (dp/dtmax). In acute myocardial necrosis "delayed reperfusion arrhythmias" are almost completely abolished at a dose of 1.6 mg/kg + 50 micrograms/kg x min. Thus, because of its antiarrhythmic potency, further experimental and clinical testing of the new compound seems promising.
Chiladakis
I
I
University Hospital, Department of Cardiology-Angiology, Münster/Westf.
Hindricks
G
G
Haverkamp
W
W
Vogt
J
J
Gülker
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D015425:Myocardial Reperfusion
D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; C061808:bipranol