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目的 观察钙调蛋白拮抗剂W -7对离体兔心实验性尖端扭转型室性心动过速(TdP)的影响,并探讨其机制。方法 采用Langendorff灌流技术,在三度房室传导阻滞和低钾(1 .5mmol/L)、低镁(0 .35mmol/L)的条件下,用索他洛尔(30μmol/L)灌流离体雌兔心脏,建立TdP模型。36只雌兔心脏随机分为索他洛尔组和W 7低浓度( 20μmol/L)、中浓度( 50μmol/L)、高浓度( 100μmol/L)干预组,每组各9只兔。灌流全程同步记录不同起搏周长下的心电图和左室内、中、外三层心肌的单相动作电位复极时程,并观察各组QT间期、跨室壁心肌复极离散度(TDR)、早期后除极(EAD)和TdP的诱发率。结果 索他洛尔逆频率依赖性延长兔QT间期和增大左室三层心肌TDR,并有较高的EAD(100% )和TdP(78% )诱发率。W 7浓度依赖性地抑制EAD诱发率(20μmol/L为56%, 50μmol/L为44%, 100μmol/L为11% )和TdP诱发率(20μmol/L为44%, 50μmol/L为22%,100μmol/L为11% ),但对QT间期和TDR均无影响。结论 抑制钙调蛋白活性能够抑制离体兔心实验性TdP的发生,这种作用主要通过抑制EAD的机制而非通过影响跨室壁复极异质性的机制来发挥。
Objective To investigate the effect of calmodulin antagonist W-7 on experimental torsades de pointes (TdP) in isolated rabbit hearts and its mechanism. Methods Langendorff perfusion technique was used to perfuse sotalol (30μmol / L) under the conditions of third degree atrioventricular block and low potassium (1.5mmol / L) and low magnesium (0.35mmol / L) Body female rabbit heart, the establishment of TdP model. Thirty-six female rabbits were randomly divided into Sotalol group and W7 low concentration (20μmol / L), medium concentration (50μmol / L) and high concentration (100μmol / L) intervention groups. The electrocardiogram (ECG) and the repolarization duration of single-phase action potentials in the left, middle, and third layers of myocardium were recorded synchronously with different pacing circumference and the changes of QT interval, transmural myocardial repolarization dispersion (TDR ), Early post-depolarization (EAD) and induction of TdP. Results Sotalol delayed the QT interval and increased the TDR of left ventricular tertiary myocardium in a frequency-dependent manner, with higher rates of EAD (100%) and TdP (78%) induction. W 7 inhibited EAD-induced rate (56% for 20μmol / L, 44% for 50μmol / L, 11% for 100μmol / L) and TdP-induced rate (44% for 20μmol / L and 22% for 50μmol / , 100μmol / L was 11%), but had no effect on QT interval and TDR. Conclusion Inhibition of calmodulin activity can inhibit the occurrence of experimental TdP in isolated rabbit heart. This effect is exerted mainly by inhibiting the mechanism of EAD rather than by affecting the transmural repolarization heterogeneity mechanism.