In silico investigation of the short QT syndrome, using human ventricle models incorporating electromechanical coupling.
In silico investigation of the short QT syndrome, using human ventricle models incorporating electromechanical coupling.
复制标题
使用结合机电耦合的人体心室模型对短 QT 综合征进行计算机研究。
DOI：
10.3389/fphys.2013.00166
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发表时间：
2013
影响因子：
4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Adeniran I;Hancox JC;Zhang H
短QT综合征（SQTS）的遗传形式是由于心脏离子通道突变导致心室复极加速、心律失常和心源性猝死而产生的。实验和模拟研究的结果表明，耐火度和组织易损性的变化产生了有利于再入的基质。SQTS的潜在机电后果还不太清楚。本研究的目的是利用机电耦合的人体心室模型来探索SQTS的机电后果。方法与结果：Rice等人的力学模型与Tusscher等人的心室细胞模型耦合。纳入了先前验证的SQT变体1和3的K+通道公式。在考虑拉伸激活通道电流（Isac）和不考虑拉伸激活通道电流（Isac）的情况下，评估了SQTS突变对[Ca2+]i瞬态、肌节长度缩短和单细胞水平收缩力的功能影响。在没有Isac的情况下，在1Hz的刺激频率下，SQTS突变产生了[Ca2+]i瞬态振幅、肌节长度缩短和收缩力的显著降低。当加入Isac时，sqts相关动作电位缩短对Ca2+瞬态、肌节缩短和收缩力的影响有相当大的衰减。然后将单细胞模型合并到三维人体心室组织模型中。与对照相比，在SQTS设置中，最大变形的时间延迟。结论：Isac的掺入似乎是模拟sqt1和3突变对心脏机电耦合的功能影响的重要考虑因素。虽然很少有证据表明SQTS患者的心脏收缩功能严重受损，但我们的3D模拟与报道的心室复极和机械收缩结束之间分离的证据定性相关。
Introduction: Genetic forms of the Short QT Syndrome (SQTS) arise due to cardiac ion channel mutations leading to accelerated ventricular repolarization, arrhythmias and sudden cardiac death. Results from experimental and simulation studies suggest that changes to refractoriness and tissue vulnerability produce a substrate favorable to re-entry. Potential electromechanical consequences of the SQTS are less well-understood. The aim of this study was to utilize electromechanically coupled human ventricle models to explore electromechanical consequences of the SQTS. Methods and Results: The Rice et al. mechanical model was coupled to the ten Tusscher et al. ventricular cell model. Previously validated K+ channel formulations for SQT variants 1 and 3 were incorporated. Functional effects of the SQTS mutations on [Ca2+]i transients, sarcomere length shortening and contractile force at the single cell level were evaluated with and without the consideration of stretch-activated channel current (Isac). Without Isac, at a stimulation frequency of 1Hz, the SQTS mutations produced dramatic reductions in the amplitude of [Ca2+]i transients, sarcomere length shortening and contractile force. When Isac was incorporated, there was a considerable attenuation of the effects of SQTS-associated action potential shortening on Ca2+ transients, sarcomere shortening and contractile force. Single cell models were then incorporated into 3D human ventricular tissue models. The timing of maximum deformation was delayed in the SQTS setting compared to control. Conclusion: The incorporation of Isac appears to be an important consideration in modeling functional effects of SQT 1 and 3 mutations on cardiac electro-mechanical coupling. Whilst there is little evidence of profoundly impaired cardiac contractile function in SQTS patients, our 3D simulations correlate qualitatively with reported evidence for dissociation between ventricular repolarization and the end of mechanical systole.
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影响因子：
20.1
作者：
Alvarez, BV;Pérez, NG;Cingolani, HE
通讯作者：
Cingolani, HE
影响因子：
4.3
作者：
Adeniran I;McPate MJ;Witchel HJ;Hancox JC;Zhang H
通讯作者：
Zhang H
影响因子：
37.8
作者：
Cheng A;Nguyen TC;Malinowski M;Daughters GT;Miller DC;Ingels NB Jr
通讯作者：
Ingels NB Jr
影响因子：
9.3
作者：
Bett, GCL;Sachs, F
通讯作者：
Sachs, F
影响因子：
3
作者：
BUSTAMANTE, JO;RUKNUDIN, A;SACHS, F
通讯作者：
SACHS, F