心脏收缩调节通过β1-肾上腺素能受体激活增加在晶体灌流正常兔心中的动作电位持续时间离散度并降低心室颤动阈值。
Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via β1-adrenoceptor activation in the crystalloid perfused normal rabbit heart.
机构信息
Cardiology Group, Department of Cardiovascular Sciences, University of Leicester, UK.
School of Clinical and Experimental Medicine, University of Birmingham, UK.
出版信息
Int J Cardiol. 2014 Mar 1;172(1):144-54. doi: 10.1016/j.ijcard.2013.12.184. Epub 2014 Jan 8.
BACKGROUND/OBJECTIVES: Cardiac contractility modulation (CCM) is a new treatment being developed for heart failure (HF) involving application of electrical current during the absolute refractory period. We have previously shown that CCM increases ventricular force through β1-adrenoceptor activation in the whole heart, a potential pro-arrhythmic mechanism. This study aimed to investigate the effect of CCM on ventricular fibrillation susceptibility.
METHODS
Experiments were conducted in isolated New Zealand white rabbit hearts (2.0-2.5 kg, n=25). The effects of CCM (± 20 mA, 10 ms phase duration) on the left ventricular basal and apical monophasic action potential duration (MAPD) were assessed during constant pacing (200 bpm). Ventricular fibrillation threshold (VFT) was defined as the minimum current required to induce sustained VF with rapid pacing (30 × 30 ms). Protocols were repeated during perfusion of the β1-adrenoceptor antagonist metoprolol (1.8 μM). In separate hearts, the dynamic and spatial electrophysiological effects of CCM were assessed using optical mapping with di-4-ANEPPS.
RESULTS
CCM significantly shortened MAPD close to the stimulation site (Basal: 102 ± 5 [CCM] vs. 131 ± 6 [Control] ms, P<0.001). VFT was reduced during CCM (2.6 ± 0.6 [CCM] vs. 6.1 ± 0.8 [Control] mA, P<0.01) and was correlated (r(2)=0.40, P<0.01) with increased MAPD dispersion (26 ± 4 [CCM] vs. 5 ± 1 [Control] ms, P<0.01) (n=8). Optical mapping revealed greater spread of CCM induced MAPD shortening during basal vs. apical stimulation. CCM effects were abolished by metoprolol and exogenous acetylcholine. No evidence for direct electrotonic modulation of APD was found, with APD adaptation occurring secondary to adrenergic stimulation.
CONCLUSIONS
CCM decreases VFT in a manner associated with increased MAPD dispersion in the crystalloid perfused normal rabbit heart.
背景/目的：心脏收缩调节（CCM）是一种新的心力衰竭（HF）治疗方法，涉及在绝对不应期应用电流。我们之前已经表明，CCM 通过β1-肾上腺素能受体在整个心脏中的激活来增加心室力，这是一种潜在的致心律失常机制。本研究旨在研究 CCM 对室颤易感性的影响。
方法
在新西兰白兔心脏（2.0-2.5 公斤，n=25）的离体实验中进行。在恒定起搏（200 bpm）期间评估 CCM（±20 mA，10 ms 相位持续时间）对左心室基底和顶部单相动作电位持续时间（MAPD）的影响。室颤阈值（VFT）定义为在快速起搏（30×30 ms）下诱发持续室颤所需的最小电流。在β1-肾上腺素能受体拮抗剂美托洛尔（1.8 μM）灌注期间重复方案。在单独的心脏中，使用 di-4-ANEPPS 进行光学映射评估 CCM 的动态和空间电生理效应。
结果
CCM 显著缩短了接近刺激部位的 MAPD（基底：102±5 [CCM] 与 131±6 [对照] ms，P<0.001）。CCM 期间 VFT 降低（2.6±0.6 [CCM] 与 6.1±0.8 [对照] mA，P<0.01），与 MAPD 离散度增加相关（r（2）=0.40，P<0.01）（n=8）。光学映射显示，在基底刺激时，CCM 诱导的 MAPD 缩短传播更大。CCM 作用被美托洛尔和外源性乙酰胆碱消除。未发现对 APD 的直接电紧张调制的证据，APD 适应发生在肾上腺素能刺激之后。
结论
CCM 以与结晶液灌注正常兔心中 MAPD 离散度增加相关的方式降低 VFT。
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