OBJECTIVETo investigate the mechanism of drug-induced torsade de pointes (Tdp) in dogs.

METHODSIn arterially perfused canine left ventricular wedge preparations, the action potential duration (APD) of the endocardial (Endo), midmyocardial (M) and epicardial (Epi) myocytes, and transmural electrocardiogram (ECG) were recorded simultaneously. The effects of different concentrations of D-Sotalol on APD, transmural dispersion of repolarization (TDR), early after depolarization (EAD) and Tdp were observed.

RESULTSD-Sotalol prolonged APD of the Endo, M and Epi cells in a concentration-dependent manner from 0-100 µmol/L, and increased TDR due to a preferential APD prolongation of the M cells relative to Epi and Endo cells. The application of D-Sotalol elicited EAD, R on T ventricular premature beats, transmural reentry and Tdp in the M cells.

CONCLUSIONEAD and R on T ventricular premature beats induced by D-Sotalol in M cells triggers Tdp, which is maintained by TDR increment and transmural reentry.