Characterization of antiarrhythmic drugs by alternating current induced arrhythmias in isolated heart tissues.
A new method for inducing arrhythmias or asystolia by the application of a 50 HZ alternating current (ac) to electrically driven heart preparations has been developed and applied to isolated left atria and right ventricular papillary muscles of the guinea-pig. An increase in driving frequency from 1 to 3 HZ effects a significant reduction of the threshold of ac-arrhythmia in guinea-pig papillary muscles but no change in atria. A decrease in temperature from 31 degrees C to 25 degrees C and an increase in [Ca2+]0 from 1.25 to 5 mmol/l elevates threshold for ac-arrhythmia and -asystolia. The fast sodium channel inhibitors quinidine, carticaine and benzylamino-5,6-dihydro-8,9-dimethoxy-imidazo-5,1-a-isoquinoline hydrochloride (HE-36) increase threshold of ac-arrhythmia in left atria and papillary muscles, whereas the slow channel inhibitor verapamil is ineffective in concentrations up to 6 mumol/l. Threshold of ac-arrhythmia is elevated by quinidine predominantly in papillary muscles. Carticaine and HE-36 are effective in left atria and papillary muscles to almost the same extent. Threshold of ac-asystolia is increased mainly in papillary muscles by quinidine and HE-36; carticaine produces a similar increase in left atria and papillary muscles. Verapamil even leads to a decrease in threshold predominantly in papillary muscles. It is concluded that model arrhythmias induced by alternating current are brought about mainly by an increase in Na+-conductance of cardiac cell membranes. The negative chronotropic potency in right atria occurs in the sequence verapamil greater than quinidine greater than carticane approximately HE-36. The negative inotropic potency in papillary muscle occurs in the same sequence but HE-36 increases force of contraction.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D013696:Temperature
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D007546:Isoquinolines; D010276:Parasympatholytics; C026136:HE 36; D002118:Calcium