Verkerk A O, Veldkamp M W, Coronel R, Wilders R, van Ginneken A C
Department of Physiology, Cardiovascular Research Institute Amsterdam, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Cardiovasc Res. 2001 Jul;51(1):30-40. doi: 10.1016/s0008-6363(01)00246-2.
The delayed phase of ventricular arrhythmias during acute ischemia (phase-1b arrhythmia) is associated with depletion of catecholamines and cell-to-cell uncoupling between depressed depolarized intramural ischemic region and surviving cells in subepicardium and subendocardium. In the present study we determined the effects of uncoupling and catecholamines on development of proarrhythmic afterdepolarizations.
Depressed depolarized ischemic region was simulated by a passive electronic circuit with a potential of -73, -53, -33 or -13 mV. Using patch-clamp methodology, single sheep Purkinje and ventricular cells were coupled to the simulated ischemic region via a variable conductance. By varying coupling conductance, we were able to selectively study the effects of various degrees of uncoupling.
At strong coupling, cells were inexcitable and depolarized to potentials near those of the simulated ischemic region. Excitability, action potential duration and resting potential increased with progressive uncoupling. In a critical range of uncoupling, ventricular and "high-plateau" Purkinje cells developed early afterdepolarizations when the potential of the simulated ischemic region was -13 mV. Norepinephrine (1 microM) frequently induced early and delayed afterdepolarizations in both ventricular and Purkinje cells, but these afterdepolarizations were only present during uncoupling when the potential of the simulated ischemic region was -33 mV or more positive.
In a critical range of uncoupling, afterdepolarizations were present when the potential of the simulated ischemic region was -33 or -13 mV, suggesting that triggered activity plays a role in phase-1b arrhythmias when surviving layers uncouple from a highly depolarized intramural ischemic region.
急性缺血期间室性心律失常的延迟期（1b期心律失常）与儿茶酚胺耗竭以及心内膜下和心外膜下缺血区域内去极化减弱的细胞与存活细胞之间的细胞间解偶联有关。在本研究中，我们确定了解偶联和儿茶酚胺对促心律失常后去极化发生发展的影响。
通过具有-73、-53、-33或-13 mV电位的无源电子电路模拟去极化减弱的缺血区域。采用膜片钳技术，将单个绵羊浦肯野细胞和心室细胞通过可变电导与模拟缺血区域耦联。通过改变耦联电导，我们能够选择性地研究不同程度解偶联的影响。
在强耦联时，细胞不可兴奋，并去极化至接近模拟缺血区域的电位。随着解偶联程度的增加，兴奋性、动作电位时程和静息电位均增加。在一个关键的解偶联范围内，当模拟缺血区域的电位为-13 mV时，心室和“高平台”浦肯野细胞出现早期后去极化。去甲肾上腺素（1 microM）经常在心室和浦肯野细胞中诱发早期和延迟后去极化，但这些后去极化仅在解偶联期间出现，此时模拟缺血区域的电位为-33 mV或更正。
在一个关键的解偶联范围内，当模拟缺血区域的电位为-33或-13 mV时出现后去极化，这表明当存活层与高度去极化的壁内缺血区域解偶联时，触发活动在1b期心律失常中起作用。
