Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium
Early termination of spiral wave reentry by combined blockade of Na+ and L-type Ca2+ currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium
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DOI：
10.1016/j.hrthm.2009.01.022
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发表时间：
2009-05-01
期刊：
影响因子：
5.5
通讯作者：
Kodama, Itsuo
中科院分区：
文献类型：
--
作者：
Ishiguro, Yuko S.;Honjo, Haruo;Kodama, Itsuo
背景抗心律失常药物对螺旋波折返的影响是一个中心问题，以期更好地了解它们的益处和风险。目的我们观察了分别阻断钠电流和L钙电流(I-Na和I-Ca，I-L)的匹西卡胺和/或维拉帕米对螺旋波折返的影响。方法采用冷冻消融法(n=32)在兔心脏建立二维心外膜心肌肌层，并用高分辨率光学标测技术分析其动作电位信号。结果在持续刺激过程中，匹西卡胺(3-5mU M)引起传导速度(CV；在5赫兹时降低20%-54%)，而不影响动作电位时程(Apd)。维拉帕米(3mU M)引起动作电位时程缩短(5赫兹时缩短16%)，但对CV无影响。在匹西卡胺或维拉帕米存在的情况下，诱发的室性心动过速(VT)更持久。持续性室速(S)/所有室速的发生率分别为58%+/-9%和22%+/-9%，对照组为62%+/-10%和22%+/-8%。使用匹西卡胺的SWS的特征是绕较长的功能阻滞线(FBL)旋转较慢，而使用维拉帕米的SWS特征是绕较短的FBL旋转较快。联合应用3MU M匹西卡胺和3MU维拉帕米可使VT提前终止(持续性VTS/所有VTS：2%+/-2%，对照组为29%+/-9%)；SWS表现出广泛的漂移和递减的传导，导致其自发消失。结论阻断I-Na或I-Ca，I-(L)均能稳定兔心室肌二维心外膜层的SWS，以帮助其持续，而阻断这两种电流则使SWS不稳定，从而促进其终止。
BACKGROUND Modification of spiral wave (SW) reentry by antiarrhythmic drugs is a central issue to be challenged for better understanding of their benefits and risks.OBJECTIVE We investigated the effects of pilsicainide and/or verapamil, which block sodium and L-type calcium currents (I-Na and I-Ca,I- L), respectively, on SW reentry.METHODS A two-dimensional epicardial ventricular muscle Layer was created in rabbit hearts by cryoablation (n = 32), and action potential signals were analyzed by high-resolution optical mapping.RESULTS During constant stimulation, pilsicainide (3-5 mu M) caused a frequency-dependent decrease of conduction velocity (CV; by 20%-54% at 5 Hz) without affecting action potential duration (APD). Verapamil (3 mu M) caused APD shortening (by 16% at 5 Hz) without affecting CV. Ventricular tachycardias (VTs) that were induced were more sustained in the presence of either pilsicainide or verapamil. The incidence of sustained VTs (>30 s)/all VTs per heart was 58% +/- 9% for 5 mu M pilsicainide vs. 22% +/- 9% for controls and 62% +/- 10% for 3 mu M verapamil vs. 22% +/- 8% for controls. The SWs with pilsicainide were characterized by slower rotation around Longer functional block lines (FBLs), whereas those with verapamil were characterized by faster rotation around shorter FBLs. Combined application of 3 mu M pilsicainide and 3 mu M verapamil resulted in early termination of VTs (sustained VTs/all VTs per heart: 2% +/- 2% vs. 29% +/- 9% for controls); SWs showed extensive drift and decremental conduction, leading to their spontaneous annihilation.CONCLUSION Blockade of either I-Na, or I-Ca,I- (L) stabilizes SWs in a two-dimensional epicardial Layer of rabbit ventricular myocardium to help their persistence, whereas blockade of both currents destabilizes SWs to facilitate their termination.