摘要
本文旨在分析酸中毒对心脏电生理活动的影响,探讨其诱发室性心律失常的机制.首先建立了具有pH和钙/钙调素依赖蛋白激酶Ⅱ(calcium/calmodulin dependent protein kinaseⅡ,Ca MKⅡ)调控作用的人体心室酸中毒计算模型,然后模拟了酸中毒过程中细胞和组织电活动的变化,并定量分析了心电图的改变情况.实验结果表明:在酸中毒期间,细胞动作电位时程的缩短和复极离散度的降低导致心电图QT间期缩短、T波幅值和宽度减小.同时,细胞静息电位的抬高和最大去极化速率的降低也促进了组织电兴奋的缓慢传导和传导阻滞.另外,酸中毒后的初期,肌浆网钙超载促进钙释放增多,导致细胞产生延迟后除极(delayed afterdepolarization,DADs),使心电图上表现为室性早搏.而缓慢传导、传导阻滞和室性早搏有利于折返波的产生,进而发展为室速.因此,酸中毒后细胞的触发活动是诱发室性心律失常的主要原因之一.
In this paper,a human ventricular acidotic model with pathophysiological consequences of acidosis,such as reduced p H and highly activated calcium/calmodulin dependent protein kinase Ⅱ(Ca MK Ⅱ),was developed to analyze the functional influence of acidosis on cardiac electrical activity and ventricular arrhythmia.Dynamic changes of cellular and tissue electrical activity were simulated and the acidosis-induced changes of electrocardiogram waveform were quantified.Results demonstrated that acidosis led to shortened action potential duration and decreased transmural dispersion of repolarization,resulting in reduced QT interval and shortened amplitude and width of T wave.In addition,acidosis also resulted in high resting membrane potential and reduced maximum upstroke velocity,leading to the generation of slow conduction and conduction block.Most importantly,at the early stage of the post acidosis,sarcoplasmic reticulum calcium load increased calcium leak,leading to delayed afterdepolarizations in the cellular membrane potential and premature ventricular contractions in the cardiac tissue model.Slow conduction,conduction block and delayed afterdepolarizations collectively promote and facilitate the formation and maintenance of ventricular re-entry,which may convert into ventricular tachycardia.Therefore,triggered activities induced during post acidosis period play an important role in the genesis of post acidosis arrhythmias.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2016年第7期716-724,共9页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(61571165)~~
关键词
计算机建模与仿真
心律失常
心电图
延迟后除极
computation modeling and simulation
arrhythmias
electrocardiogram
delayed afterdepolarization