Sodium-calcium exchange initiated by the Ca2+ transient -: An arrhythmia trigger within pulmonary veins
Sodium-calcium exchange initiated by the Ca2+ transient -: An arrhythmia trigger within pulmonary veins
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DOI：
10.1016/j.jacc.2005.12.023
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发表时间：
2006-03-21
影响因子：
24
通讯作者：
Po, SS
中科院分区：
文献类型：
--
作者：
Patterson, E;Lazzara, R;Po, SS
目的 对缩短动作电位期间 Ca2+ 瞬变增加或延长可引起早期后除极 (EAD) 并通过增强前向钠钙 (Na-Ca) 交换引发心律失常的假设进行了检查。 背景 由于肺静脉具有所有心脏组织中最短的动作电位，因此我们在干预期间在犬肺静脉袖中检查了这一假设，进一步缩短了动作电位并增加了钙瞬变。从灌注的犬肺静脉中获得双极电极、细胞内微电极和等长力（Ca2+瞬变的替代标记）记录。结果在增加收缩力的干预期间观察到复极末期（EAD）的升高和延长；异丙肾上腺素或去甲肾上腺素（3.2 X 10(-11) 至 3.2 X 10(-7)M）、低温和起搏（期外收缩后增强、起搏后暂停）。 EAD 的形成可被兰尼定 (10 muM) 阻止，或通过暂时增加 [Ca2+] 从 1.35 至 5 mM（抑制正向 Na-Ca 交换）来逆转。用 30 mM LiCl 替代 30 mM NaCl（刺激正向 Na-Ca 交换）后，重新引入正常 Tyrode 溶液 (Na+ 130 mM) 可增强起搏诱导的 EAD。使用去甲肾上腺素或异丙肾上腺素 (3.2 X 10(-8)M) + 乙酰胆碱 (10-7M)（分别增强 Ca2+ 瞬变并进一步缩短缩短的动作电位），观察到心动过速暂停引发的心律失常（1,132 +/- 153 次/分钟）持续 > 1 s。通过抑制 Ca2+ 瞬态（兰尼碱）或暂时增加 [Ca2+](o) 来防止快速放电。结论 数据显示，在灌注的犬肺静脉中形成 EAD，并通过增加 Ca2+ 瞬态和增加 Na-Ca 交换电流而增强。随着乙酰胆碱随后缩短动作电位，心动过速暂停会触发 PV 套管内的快速放电。
OBJECTIVES The hypothesis that an increased or prolonged Ca2+ transient during an abbreviated action potential can give rise to early afterdepolarizations (EADs) and triggered arrhythmia by enhanced forward sodium-calcium (Na-Ca) exchange was examined.BACKGROUND Because pulmonary veins have the shortest action potential of any cardiac tissue, we examined this hypothesis in canine pulmonary vein sleeves during interventions further shortening the action potential and increasing the calcium transient.METHODS Extracellular bipolar electrode, intracellular microelectrode, and isometric force (a surrogate marker for the Ca2+ transient) recordings were obtained from superfused canine pulmonary veins.RESULTS An elevation and prolongation of the terminal phase of repolarization (EADs) were observed during interventions increasing contractile force; isoproterenol or norepinephrine (3.2 X 10(-11) to 3.2 X 10(-7)M), hypothermia, and pacing (post-extrasystolic potentiation, postpacing pause). The EAD formation was prevented by ryanodine (10 mu M) or reversed by transiently increasing [Ca2+], from 1.35 to 5 mM (inhibition of forward Na-Ca exchange). Pacing-induced EADs were enhanced by re-introduction of normal Tyrode solution (Na+ 130 mM) after substitution of 30 mM NaCl with 30 mM LiCl (stimulation of forward Na-Ca exchange). With norepinephrine or isoproterenol (3.2 X 10(-8)M) + acetylcholine (10-7M) (to enhance the Ca2+ transient and further shorten the abbreviated action potential, respectively), tachycardia-pause initiated arrhythmia (1,132 +/- 153 beats/min) lasting > 1 s was observed. Rapid firing was prevented by either suppression of the Ca2+ transient (ryanodine) or transiently increasing [Ca2+](o).CONCLUSIONS The data show EAD formation in superfused canine pulmonary veins, enhanced by an increased Ca2+ transient and increased Na-Ca exchange current. With subsequent shortening of the action potential with acetylcholine, tachycardia-pause triggers rapid firing within the PV sleeve.