| Torsade de poindes(TdP) is a term named by Dessertenne for a life threatening form of polymorphic ventricular tachycardia(VT) which typically is seen in the setting of abnormal QT-prolongation including the congenital long QT syndrome(LQTS) and acquired abnormal QT-prolongation. The most typical ECG characters of TdP is the wave rotation around the isoelectric baseline, and its is about 200 - 300 ms. The exact electro- physiologic mechanism of TdP is under intensive investigation. It has been proposed that early afterdepolarizations (EADs) trigger the arrhythmia. And it has been suggested that an increased inhomogeneity (dispersion) of ventricular repolarization contributed to the genesis of TdP and the characteristic undulating pattern of the QRS complex was thought to be a special form of reentry. The majority of cases of acquired TdP are due to drug -induced with class III and antihistamine in which sotalol and terfenadine are the most important relevant medicine which prolong the QT interval by delaying repolarization , particularly in those with concomitant hypokalemia and bradycardia.The present experiment aimed to reproduce conditions that are clinically known to be associated with an increased propensity to the development of TdP by perfusion sotalol and terfenadine in isolated rabbit heart and to investigate the mechanism of TdP and proarrythmia potency of medicine.MethodsRabbit hearts(perfused with Langendorff technique) in vitro with cauterize-induced III atrio-ventricular block(AVB),TdP was induced in the presence of sotalol and terfenadine, when the concentration of potassium and magnesium in the perfusate was lowered to 2.0 and 0.35mM(modified tyrode's solution).Volume-conduced electrocardiogram to simulate limb I and AVL and left ventricular endocardium monophasic action potentials (MAP) were recorded simultaneously.The effect of sotalol and terfenadine with various concentrations X 10, 410; 810, 810, 16 X 10~ 1610M) were studied in 13 isolated rabbit hearts. ResultsEarly after depolarizations(EADs) , triggered activity(TA) and TdP were not induced with tyrode's solution. Compared with baseline, sotalol and terfenadine prolonged QT interval and APD at different concentrations with different pacing cycle lengthes, which were from 400ms to 2400 ms. EADs were recorded in 13 rabbit hearts. Triggers of 1 to 4 beats (TA) were also recorded in 13 rabbit hearts. TdP of 5 up to 21 beats were recorded in 13 rabbit hearts. Using various Sotalol and terfenadine concentrations ( 4 X 10 4 X 10 8 8 10; 1610 1610M) concurrently with modified tyrode's solution when the pacing cycle length was more than 1400ms, we observe total of 44 episodes of TdP in 10/13 hearts. While the concentration of sotalol and terfenadine was 410, 410; 810 810; 16 X 10 16M, we found TdP in 3,610 rabbit hearts respectively and the episodes of TdP induced were 7,11,26. All episodes of TdP terminated spontaneously.ConclusionRabbit hearts(perfused with Langendorff technique) in vitro ,TdP can be induced by means of bradycardia in the presence of conbinated with sotalol and terfenadine in the modified tyrode's solution. EADs were associated with TdP. Sotalol and terfenadine induced TdP was obviously in highest concentration of the medicine. |
