EFFECTS OF MAGNESIUM ON POLYMORPHIC VENTRICULAR TACHYCARDIAS INDUCED BY ACONITINE

We examined the effects of Mg2+ On aconitine-induced polymorphic ventr icular tachycardias (PVT) in excised rabbit hearts under Langendorff p erfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectro de technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronar y 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 aconitin e-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but <3 m M Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2concentrations less than or equal to 5 mM in the coronary perfusate pr evented development of PVT by aconitine. Intracoronary application of 10 mu M tetrodotoxin (TTX) also restored aconitine-induced PVT to sinu s 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 Purkinj e-muscle preparations, spontaneous action potentials (AP) from slow di astolic depolarization appeared after aconitine at the maximum diastol ic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increa sed in rate and then developed triggered activity arising from early a fterdepolarization (EAD). EAD induced by aconitine always appeared fir st in Purkinje fibers and later in muscle fibers. Once triggered activ ities 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 bu t also in preventing aconitine-induced PVT based on triggered activity from EADs.