摘要
目的 对临床易发尖端扭转型室性心动过速（TDP）的情况进行模拟，利用Langendorff逆灌流技术灌注离体兔心，研究特非那丁促TDP的机制。方法 烧灼法制备Ⅲ°房室传导阻滞离体兔心模型，应用不同浓度的特非那丁低钾镁台氏液，利用Langendorff逆灌流技术灌注兔心，以不同周长起搏，利用慢频率和刺激周长骤变方法诱发早期后除极（EADs）、TDP。结果 基础台氏液和低钾镁台氏液（MT）灌流下均未见EADs、TDP；各浓度特非那丁低钾镁台氏液灌流都可延长QT间期和单向动作电位复极达90％时限（MA-PD90），10／18例记录到EADs，起搏周长1400～2400ms。10／18例诱发出TDP，7／18例经过刺激周长骤变诱发出TDP，以300-2300ms为多（6／18例），MT＋特非那丁浓度8×10^-6mmol／L时诱发TDP频率最高，为66．7％。结论 在离体兔心，特非那丁MT灌注呈浓度及频率依赖性延长MA-PD90；EAD及其引起的触发活动（TA）是诱发TDP的基础。
Objective To reproduce conditions that were 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 The isolated rabbit hearts, with cauterizeinduced Ⅲ° atrio-ventricular block （AVB） , were perfused by the non-recirculating Langendorff technique and used a variety of pacing cycle length. Early after depolarizations （EADs） and TDP were induced by abrupt changes of cycle length in the presence of Tyrode＇s solution containing terfenadine and 50% reduced the concentration of potassium and magnesium （low K＋ and Mg^＋＋ ）. Results No early after depolarizations （EADs） and triggered activity （TA） or TDP was induced with tyrodes solution and modified tyrode＇s solution. Compared with baseline, terfenadine prolonged QT interval and MAPD90 at different concentration with different pacing cycle length, which was from 400ms to 2 400ms. EADs were recorded in 10/18 rabbit hearts. TDP episodes were induced by terfenadine （ concentration was 1×10^-6, 2×10^-6, 4×10^-6 and 8×10^-6M , 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. Conclusion In this Langendorff perfused rabbit hearts, terfenadine prolonged MAPD90 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 are associated with TDP.
出处
《中国心血管杂志》
2006年第2期92-95,共4页
Chinese Journal of Cardiovascular Medicine
