Experimental Study Of Mechanism On Torsade De Pointes Induced By Terfenadine

Objective The present experiment aimed to reproduce conditions that are clinically known to be associated with an increased propensity to the development of torsade de pointes (TDP) by perfusion terfenadine in isolated rabbit heart, and investigate the mechanism of torsade de pointes and proarrythmia potency of the medicine.Methods Derbai male and female rabbits ( weight 2. 03?. 24 Kg ) were studied. The isolated rabbit hearts, with cauterize-induced III atrio-ventricular block (AVB) , were perfused by the non-recirculating Lanfendorff technique and used a variety of pacing cycle length (400, 600, 800, 1000, 1200, 1400, 1600, 1800, 2000, 2400ms). Early afterdepolarizations (EADs) and triggered activity (TA) and TOP were induced by abrupt changes of cycle length in the presence of Tyrode' s solution containing terfenadine (1X10-6, 2X10-6, 4X10-6,, and 8X10-6M) and 50% reduced the concentration of potassium and magnesium (low K+ and Mg++) . Volume-conduced electrocardiogram to simulate limb leads I and AVL and left ventricular endocardium monophasic action potentials ( MAP) were recorded simultaneously.Results No early afterdepolarizations (EADs) and triggered activity (TA) or TDP was induced with tyrodes solution and modified tyrode' s solution. Compared with baseline, terfenadineprolonged QT interval and APD90 at different concentration with different pacing cycle length, which was from 400ms to 2400ms. EADs were recorded in 10/18 rabbit hearts, 1/5 in males and 9/13 in females. TDP episodes is induced by terfenadine (concentration was 110, 210, 410 and 8X lOM .respectively) concurrently with modified tyrode' s solution when the pacing cycle length was more than 1600ms in 3/18 (16. 7%) hearts studied and was induced by abrupt changes of cycle length in 7/18 (38.1%) hearts .All episodes of TDP terminated spontaneously.Conclusions In this Langendorff perfused rabbit hearts, terfenadine prolonged QT interval and APD90 at different concentration with different pacing cycle length. TDP can be induced by abrupt changes of cycle length in the presence of the modified tyrode' s solution containing terfenadine. EADs were associated with TDP.