交感神经-迷走神经相互作用对心室电生理学的影响及其在β受体阻滞剂治疗中的调节。
Effects of sympatho-vagal interaction on ventricular electrophysiology and their modulation during beta-blockade.
机构信息
Cardiology group, Department of Cardiovascular Sciences, University of Leicester, UK; University Hospitals of Leicester NHS Trust, Leicester, UK.
Cardiology group, Department of Cardiovascular Sciences, University of Leicester, UK.
出版信息
J Mol Cell Cardiol. 2020 Feb;139:201-212. doi: 10.1016/j.yjmcc.2020.01.011. Epub 2020 Jan 29.
AIMS
The effects of sympatho-vagal interaction on heart rate (HR) changes are characterized by vagal dominance resulting in accentuated antagonism. Complex autonomic modulation of ventricular electrophysiology may exert prognostic arrhythmic impact. We examined the effects of concurrent sympathetic (SNS) and vagus (VNS) nerve stimulation on ventricular fibrillation threshold (VFT) and standard restitution (RT) in an isolated rabbit heart preparation with intact dual autonomic innervation, with and without beta-blockade.
METHODS AND RESULTS
Monophasic action potentials were recorded from left ventricular epicardial surface of dual-innervated isolated heart preparations from New Zealand white rabbits (n = 18). HR, VFT and RT were measured during different stimulation protocols (Protocol 1: VNS-SNS; Protocol 2: SNS-VNS) involving low- and high-frequency stimulations. A sub-study of Protocol 2 was performed in the presence of metoprolol tartrate. In both protocols, HR changes were characterized by vagal-dominant bradycardic component, affirming accentuated antagonism. During concurrent high-frequency VNS (HV), SNS prevails in lowering VFT in a frequency-sensitive manner during low (LS) or high (HS)-frequency stimulations (HV-LS: -2.8 ± 0.8 mA; HV-HS: -4.0 ± 0.9 mA, p < .05 vs. HV), with accompanying steepening of relative RT slope gradients (HV-LS: 223.54 ± 37.41%; HV-HS: 295.20 ± 60.86%, p < .05 vs. HV). In protocol 2, low (LV) and high (HV) vagal stimulations during concurrent HS raised VFT (HS-LV: 1.0 ± 0.4 mA; HS-HV: 3.0 ± 0.6 mA, p < .05 vs HS) with associated flattening of RT slopes (HS-LV: 32.40 ± 4.97%;HS-HV: 38.07 ± 6.37%; p < .05 vs HS). Metoprolol abolished accentuated antagonism in HR changes, reduced VFT and flattened RT globally during SNS-VNS.
CONCLUSIONS
Accentuated antagonism is absent in ventricular electrophysiological changes during sympatho-vagal interaction with sympathetic effect prevailing, suggesting a different mechanism at the ventricular level from heart rate effects. Metoprolol nullified accentuated antagonism with additional anti-fibrillatory effect beyond adrenergic blockade during sympatho-vagal stimulations.
目的
交感-迷走神经相互作用对心率（HR）变化的影响表现为迷走神经优势导致的明显拮抗。心室电生理的复杂自主调制可能产生心律失常的预后影响。我们在具有完整双重自主神经支配的分离兔心标本中，检查了同时刺激交感神经（SNS）和迷走神经（VNS）对室颤阈值（VFT）和标准折返（RT）的影响，β受体阻滞剂存在或不存在。
方法和结果
从新西兰白兔（n=18）的双神经支配分离心脏标本的左心室心外膜表面记录单相动作电位。在涉及低频和高频刺激的不同刺激方案（方案 1：VNS-SNS；方案 2：SNS-VNS）期间测量 HR、VFT 和 RT。在方案 2 中进行了亚研究，其中加入了酒石酸美托洛尔。在两个方案中，HR 变化的特征是迷走神经主导的心动过缓成分，证实了明显的拮抗作用。在同时进行的高频 VNS（HV）期间，SNS 以频率敏感的方式降低 VFT，在低频（LS）或高频（HS）刺激时（HV-LS：-2.8±0.8mA；HV-HS：-4.0±0.9mA，p<0.05 与 HV 相比），同时伴随相对 RT 斜率梯度变陡（HV-LS：223.54±37.41%；HV-HS：295.20±60.86%，p<0.05 与 HV 相比）。在方案 2 中，在同时进行的 HS 期间进行的低（LV）和高（HV）迷走神经刺激会升高 VFT（HS-LV：1.0±0.4mA；HS-HV：3.0±0.6mA，p<0.05 与 HS 相比），同时 RT 斜率变平（HS-LV：32.40±4.97%；HS-HV：38.07±6.37%；p<0.05 与 HS 相比）。美托洛尔在 SNS-VNS 期间消除了 HR 变化中的明显拮抗作用，降低了 VFT，并使整个 RT 变平。
结论
在交感-迷走神经相互作用期间，心室电生理变化中不存在明显的拮抗作用，交感神经占主导地位，这表明在心室水平的机制与心率效应不同。美托洛尔在交感-迷走神经刺激期间除了阻断肾上腺素能之外，还消除了明显的拮抗作用并具有额外的抗纤颤作用。
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