Mironov Sergey, Jalife José, Tolkacheva Elena G
Department of Pharmacology, Institute for Cardiovascular Research, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Circulation. 2008 Jul 1;118(1):17-25. doi: 10.1161/CIRCULATIONAHA.107.737254. Epub 2008 Jun 16.
Spatially discordant alternans (SDA) has been linked to life-threatening arrhythmias. The mechanisms underlying SDA development in cardiac tissue remain unclear.
We investigated the role of conduction velocity (CV) restitution and short-term memory in the organization and evolution of alternans in action potential duration using high-resolution optical mapping of the epicardial surface in 8 isolated, Langendorff-perfused rabbit hearts. To assess the spatial organization of alternans, we tracked the evolution of nodal lines that separate out-of-phase regions of SDA. We measured the action potential duration heterogeneity index and maximal slope of CV restitution and estimated the effects of short-term memory by calculating time constant of action potential duration accommodation (tau). We found that 2 mechanisms underlie the development of SDA in the heart, leading to 2 distinct behaviors of nodal lines. The first mechanism is based on steep CV restitution and is associated with small tau and stable nodal lines. The second mechanism is associated with short-term memory (large tau) and is characterized by shallow CV restitution and unstable behavior of nodal lines. The maximum slope of the CV restitution was steeper (18.16+/-3.34 m/s(2)) and tau was smaller (tau=4.31+/-0.33 stimuli) for areas with stable nodal lines than for areas with unstable nodal lines (6.32+/-0.96 m/s(2) and tau=10.3+/-1.84 stimuli; P<0.01).
Our results provide new insight into the mechanisms underlying SDA formation in the rabbit heart. Specifically, our results suggest that a new mechanism associated with short-term memory underlies SDA formation in the heart, in addition to steep CV restitution.
空间不协调交替(SDA)与危及生命的心律失常有关。心脏组织中SDA发生的机制仍不清楚。
我们使用8个离体的、Langendorff灌注的兔心脏的心外膜表面高分辨率光学标测技术,研究了动作电位时程中传导速度(CV)恢复和短期记忆在交替现象的组织和演变中的作用。为了评估交替现象的空间组织,我们追踪了分隔SDA不同相位区域的节点线的演变。我们测量了动作电位时程异质性指数和CV恢复的最大斜率,并通过计算动作电位时程适应的时间常数(tau)来估计短期记忆的影响。我们发现心脏中SDA的发生有两种机制,导致节点线出现两种不同的行为。第一种机制基于陡峭的CV恢复,与小的tau和稳定的节点线相关联。第二种机制与短期记忆(大的tau)相关联,其特征是CV恢复较浅且节点线行为不稳定。与具有不稳定节点线的区域相比,具有稳定节点线的区域的CV恢复最大斜率更陡峭(18.16±3.34 m/s²)且tau更小(tau = 4.31±0.33个刺激)(6.32±0.96 m/s²和tau = 10.3±1.84个刺激;P<0.01)。
我们的结果为兔心脏中SDA形成的机制提供了新的见解。具体而言,我们的结果表明,除了陡峭的CV恢复外,一种与短期记忆相关的新机制是心脏中SDA形成的基础。