EFFECTS OF MAGNESIUM ON POLYMORPHIC VENTRICULAR TACHYCARDIAS INDUCED BY ACONITINE

We examined the effects of Mg2+ On aconitine-induced polymorphic ventricular tachycardias (PVT) in excised rabbit hearts under Langendorff perfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectrode technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronary application of 0.1 mu M aconitine induced PVT 28.8 +/- 3.4 min after development of regular monomorphic ventricular tachycardias (MVT) in all 18 preparations. Application of 5 and 10 mM Mg2+ restored aconitine-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but <3 mM Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2+ concentrations less than or equal to 5 mM in the coronary perfusate prevented development of PVT by aconitine. Intracoronary application of 10 mu M tetrodotoxin (TTX) also restored aconitine-induced PVT to sinus rhythm after 3.2 +/- 0.8 min (n = 4). Although applications of 50 mu M lidocaine, 10 mu M flecainide, or 1 mu M verapamil could change PVT to MVT, they were not effective in restoring sinus rhythm. In Purkinje-muscle preparations, spontaneous action potentials (AP) from slow diastolic depolarization appeared after aconitine at the maximum diastolic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increased in rate and then developed triggered activity arising from early afterdepolarization (EAD). EAD induced by aconitine always appeared first in Purkinje fibers and later in muscle fibers. Once triggered activities started from EAD, rate, rhythm and amplitudes of APs became fast and variable. Application of 10 mM Mg2+ suppressed triggered activity from EAD as well as spontaneous activity. We concluded that increased external magnesium is effective not only in restoring sinus rhythm but also in preventing aconitine-induced PVT based on triggered activity from EADs.