Effects of antiarrhythmic agents and Mg2+ on aconitine-induced arrhythmias.
The effects of antiarrhythmic agents, including Classes I and IV and 3-10 mM Mg2+ on aconitine-induced arrhythmias were examined using a conventional microelectrode and patch clamp method in Langendorff-perfused rabbit hearts and isolated guinea-pig ventricular myocytes. Intracoronary application of 0.1 microM aconitine induced polymorphic ventricular tachycardia (PVT) which continued for more than 60 minutes. Application of aconitine to ventricular myocytes caused a prolonged action potential duration (APD) and the appearance of early afterdepolarization (EAD) together with the occurrence of an inward hump of the I-V curve around -60 to -40 mV and increased outward current at positive voltages. Application of 10 microM TTX and 5 mM or higher Mg2+ restored aconitine-induced PVT to sinus rhythm in Langendorff-perfused preparations and also shortened the prolonged APD, demonstrating the abolishment of EAD by aconitine in ventricular myocytes. However, antiarrhythmic agents did not exert such effects. In conclusion, the antiarrhythmic actions of Mg2+ and TTX in aconitine-induced arrhythmia are to abolish EAD and shorten the prolonged APD by suppression of the inward Na+ current around -60 to -40 mV.
Sawanobori
T
T
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Adaniya
H
H
Hirano
Y
Y
Hiraoka
M
M
D000157:Aconitine; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D013779:Tetrodotoxin; D008274:Magnesium; D000157:Aconitine