Agladze Konstantin, Kay Matthew W, Krinsky Valentin, Sarvazyan Narine
Pharmacology and Physiology Department, The George Washington University, 2300 Eye Street, Washington, DC 20037.
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H503-13. doi: 10.1152/ajpheart.01060.2006. Epub 2007 Mar 23.
For prevention of lethal arrhythmias, patients at risk receive implantable cardioverter-defibrillators, which use high-frequency antitachycardia pacing (ATP) to convert tachycardias to a normal rhythm. One of the suggested ATP mechanisms involves paced-induced drift of rotating waves followed by their collision with the boundary of excitable tissue. This study provides direct experimental evidence of this mechanism. In monolayers of neonatal rat cardiomyocytes in which rotating waves of activity were initiated by premature stimuli, we used the Ca(2+)-sensitive indicator fluo 4 to observe propagating wave patterns. The interaction of the spiral tip with a paced wave was then monitored at a high spatial resolution. In the course of the experiments, we observed spiral wave pinning to local heterogeneities within the myocyte layer. High-frequency pacing led, in a majority of cases, to successful termination of spiral activity. Our data show that 1) stable spiral waves in cardiac monolayers tend to be pinned to local heterogeneities or areas of altered conduction, 2) overdrive pacing can shift a rotating wave from its original site, and 3) the wave break, formed as a result of interaction between the spiral tip and a paced wave front, moves by a paced-induced drift mechanism to an area where it may become unstable or collide with a boundary. The data were complemented by numerical simulations, which was used to further analyze experimentally observed behavior.
为预防致命性心律失常,有风险的患者会植入心脏复律除颤器,该设备利用高频抗心动过速起搏(ATP)将心动过速转变为正常心律。一种被提出的ATP机制涉及起搏诱导的旋转波漂移,随后这些旋转波与可兴奋组织的边界发生碰撞。本研究为这一机制提供了直接的实验证据。在新生大鼠心肌细胞单层培养物中,通过过早刺激引发活动的旋转波,我们使用钙敏感指示剂Fluo 4来观察传播的波型。然后以高空间分辨率监测螺旋波尖端与起搏波的相互作用。在实验过程中,我们观察到螺旋波固定在心肌细胞层内的局部异质性区域。在大多数情况下,高频起搏导致螺旋活动成功终止。我们的数据表明:1)心脏单层中的稳定螺旋波倾向于固定在局部异质性或传导改变的区域;2)超速起搏可使旋转波从其原始位置移位;3)螺旋波尖端与起搏波前相互作用形成的波破裂,通过起搏诱导的漂移机制移动到一个可能变得不稳定或与边界碰撞的区域。这些数据得到了数值模拟的补充,数值模拟用于进一步分析实验观察到的行为。