Utilization of Chick Embryonic Electrocardio-grams to Detect the Proarrhythmic Actions by Antiarrhythmic Drugs

Takashi Sugiyama, Hiroyuki Miyazaki and Hideyo Shimada
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University,@9-1, Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan

Correspondence: Takashi Sugiyama, Ph.D.
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University, 9-1, Shirokane 5-chome, Minato-ku, Tokyo 108-8641, Japan
Tel and Fax; +81-03-3446-9036
E mail; sugiyamat@platinum.pharm.kitasato-u.ac.jp

Running title: Proarrhythmic actions by antiarrhythmic drugs in chick embryos

Original paper :AATEX 6(1):72-78,1999
Abstract

We have studied the pharmacological and toxicological effects of cardiovascular drugs on chick embryos using electrocardiograms in order to develop alternatives to the use of mammals. Recently, proarrhythmic actions induced by antiarrhythmic drugs have been widely studied. In this study, we investigated the pharmacological effects of antiarrhythmic drugs, Ia(procainamide), Ib(lidocaine), Ic(flecainide), II(propranolol) and IV(verapamil)types, as classified by Vaughan Williams. When a single injection of drugs was performed into the air sac of fertile eggs of White Leghorns on the 16th day of incubation, all drugs decreased HR in a dose-dependent manner. Also, when higher dosages of drugs were injected, these drugs induced various kinds of arrhythmias, i.e., S-A or A-V blocks, as shown in mammals. The intervals of PQ, QRS and QT waves varied depending on the drugs used. However, the ECG waves exhibited the same changes seen in mammals with a few exceptions. Our ECG recording system using chick embryos may be applicable for screening tests for proarrhythmic actions of antiarrhythmic drugs.

Key words: Chick embryo, alternative animal, antiarrhythmic drug, electrocardiogram, proarrhythmic action


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