Electrophysiological mechanisms of ventricular arrhythmias associated with QT interval prolongation

QT间期延长相关室性心律失常的电生理机制

• 批准号: 62570389
• 负责人: KODAMA Itsuo
• 金额: $ 1.34万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570389/
• 关键词: QT prolongation; ventricular arrhythmias; antiarrhythmic drugs; hypothyroidism; ventricular repolarization; action potential duration; リエントリー; 重症不整脈; 心筋小胞体; 細胞内Ca動態; 細胞外電位; 膜治動電位; 心室脱分極; リエントリー不整脈

Electrophysiological mechanisms of ventricular arrhythmias associated with QT interval prolongation by antiarrhythmic drugs and hypothyroidism were investigated in animal experiments. In Langendorff-perfused rabbit hearts, bepridil (1 M) caused a significant prolongation of QT interval of distant bipolar electrograms (DBEs). At 10 ,, the QT prolongation was further enhanced, and a significant prolongation of QRS duration was also observed. Polymorphous ventricular tachycardia was frequently induced by a single premature stimulus at the higher concentration. In epicardial electrograms recorded through modified bipolar electrodes, bepridil prolonged the interval from the peak negative deflection of the QRS complex to the apex of the T wave (Q-aT), which corresponded to the intracellular action potential duration (APD) at 90 % repolarization. The Q-aT prolongation was larger in the base than in the apex, resulting in a marked distortion and dispersion of repolarization. At the higher conc … More entration of bepridil, the dispersion of repolarization was much more enhanced by activation delay in the epicardial surface. These findings suggest that bepridil causes regionally different lengthening of APD in ventricular muscle leading to an increase in temporal dispersion of repolarization, and that this dispersion may be inductive for re-entrant arrhythmias when accompanied by slow conduction at toxic dose. Electromechanical characteristics of right ventricular papillary muscles isolated from rabbits 4 to 6 weeks after thyroidectomy were also investigated. Thyroidectomy resulted in a marked prolongation of both APD and the time to peak developed tension (DT). Ryanodine-sensitive components of contraction such as post-rest potentiation were largely inhibited in ventricular muscles of hypothyroidism. These results suggest that APD prolongation of ventricular muscles with hypothyroidism leading to a QT prolongation may be attributed at least in part to an inhibition of intracellular calcium dynamics. Less

通过动物实验研究了与抗心律失常药物 QT 间期延长和甲状腺功能减退相关的室性心律失常的电生理机制。在 Langendorff 灌注的兔心脏中，bepridil (1 M) 导致远端双极电图 (DBE) 的 QT 间期显着延长。 10时，QT间期延长进一步增强，QRS时限也显着延长。多形性室性心动过速经常由较高浓度的单一过早刺激引起。在通过改良双极电极记录的心外膜电图中，苯普地尔延长了从 QRS 复合波负偏转峰值到 T 波 (Q-aT) 顶点的间隔，这对应于 90% 复极时的细胞内动作电位持续时间 (APD)。 Q-aT 延长在基部比在顶点更大，导致复极化的明显扭曲和分散。当苯普地尔浓度较高时，心外膜表面的激活延迟大大增强了复极化的分散性。这些发现表明，苯普地尔引起心室肌中 APD 的区域性不同延长，导致复极的时间分散增加，并且当伴随有毒剂量的缓慢传导时，这种分散可能诱发折返性心律失常。还研究了甲状腺切除术后 4 至 6 周从兔子身上分离的右心室乳头肌的机电特征。甲状腺切除术导致 APD 和达到峰值张力 (DT) 的时间显着延长。甲状腺功能减退症的心室肌中，瑞尼定敏感的收缩成分（例如静息后增强）在很大程度上受到抑制。这些结果表明，甲状腺功能减退引起的心室肌 APD 延长导致 QT 延长可能至少部分归因于细胞内钙动力学的抑制。较少的

项目成果

Osaka T.: British Journal of Pharmacology. (1988)

Osaka T.：英国药理学杂志。

Toshiyuki,Osaka: Environmental Medicine. 31. 75-80 (1987)

Toshiyuki，大阪：环境医学。

Toshiyuki,Osaka: British Journal of Pharmacology. 93. 775-780 (1988)

Toshiyuki，大阪：英国药理学杂志。