Kis A, Végh A, Papp J G, Parratt J R
Department of Pharmacology, Albert Szent-Györgyi Medical University, Dóm tér 12, Szeged, H-6701, Hungary.
J Mol Cell Cardiol. 1999 Jun;31(6):1229-41. doi: 10.1006/jmcc.1999.0955.
Right ventricular pacing in lightly anaesthetized dogs (4x5 min periods at a pacing rate of 220 beats/min) protects against the consequences of coronary artery occlusion when this is initiated 24 h after the pacing stimulus. The main purpose of the present experiments was to determine whether repeating the pacing stimulus, at a time when protection from the initial stimulus had faded (48 h), prolonged the protection afforded against ischaemia-induced ventricular arrhythmias and other ischaemic changes (epicardial ST-segment mapping; changes in the degree of electrical inhomogeneity in the ischaemic region). Dogs were paced on two occasions, with a 48 h period between and, at different times (48, 72 and 96 h) after the second pacing stimulus, were re-anaesthetized and subjected to occlusion of the left anterior descending coronary artery. There was a marked reduction in the severity of ischaemia-induced arrhythmias 48 and 72 h after the second pacing stimulus (reduction in occlusion-induced and reperfusion-induced ventricular fibrillation, e.g. at 72 h 0/11 during occlusion and only 3/11 following reperfusion, compared to 7/21 and 10/21 respectively in the controls P<0.05). The protection had disappeared 96 h following the second pacing stimulus. Changes in ST-segment elevation and in the degree of inhomogeneity largely followed these changes in the severity of ventricular arrhythmias. The results suggest the possibility of maintaining protection against life-threatening arrhythmias following coronary occlusion by repeating a preconditioning pacing stimulus. We also demonstrate that this prolonged protection afforded by repeated cardiac pacing is mediated by nitric oxide, since the marked antiarrhythmic effect observed, e.g. 72 h after the second pacing stimulus, was abolished when S-(2-aminoethyl)-isothiourea (AEST), a particularly selective inhibitor of iNOS, had been administered before coronary artery occlusion.
在轻度麻醉的犬中进行右心室起搏（以220次/分钟的起搏频率进行4×5分钟时段），当在起搏刺激后24小时开始冠状动脉闭塞时，可预防冠状动脉闭塞的后果。本实验的主要目的是确定在对初始刺激的保护作用消退时（48小时）重复起搏刺激是否能延长对缺血性室性心律失常和其他缺血性变化（心外膜ST段标测；缺血区域电不均匀程度的变化）的保护作用。犬分两次进行起搏，两次之间间隔48小时，在第二次起搏刺激后的不同时间（48、72和96小时）再次麻醉并进行左前降支冠状动脉闭塞。在第二次起搏刺激后48和72小时，缺血性心律失常的严重程度显著降低（闭塞诱导和再灌注诱导的心室颤动减少，例如在72小时时，闭塞期间为0/11，再灌注后仅为3/11，而对照组分别为7/21和10/21，P<0.05）。第二次起搏刺激后96小时保护作用消失。ST段抬高和不均匀程度的变化在很大程度上随室性心律失常严重程度的这些变化而变化。结果表明，通过重复预处理起搏刺激有可能维持对冠状动脉闭塞后危及生命的心律失常的保护作用。我们还证明，重复心脏起搏所提供的这种延长的保护作用是由一氧化氮介导的，因为在冠状动脉闭塞前给予特别选择性的诱导型一氧化氮合酶抑制剂S-(2-氨乙基)-异硫脲（AEST）时，例如在第二次起搏刺激后72小时观察到的显著抗心律失常作用被消除。
