Curtis M J
Rayne Institute, St Thomas's Hospital, London, United Kingdom.
Cardiovasc Res. 1991 Dec;25(12):1010-22. doi: 10.1093/cvr/25.12.1010.
The aim was to develop a new model for determining which factors associated with ischaemia and reperfusion are sufficient for arrhythmogenesis, and to use the model for examining regional hyperkalaemia and K+ washout. DESIGN AND EXPERIMENTAL MATERIAL: Rabbit hearts (n = 150) were perfused with a buffered solution containing K+ in the normal range (2,3,4, or 5 mM). The circumflex coronary artery was perfused independently with a similar solution at a similar rate. A regional increase in K+ concentration was produced, followed by restoration of control K+ to mimic regional changes in K+ during ischaemia and reperfusion.
Regional hyperkalaemia (K+ = 9, 12, 15, or 18 mM) mimicked (concentration dependently) the known effects of regional ischaemia on the ECG in three important respects, producing ventricular arrhythmias, regional changes in ECG configuration, and regional alternans. The relationship between arrhythmias and K+ was bell shaped with a peak in susceptibility at 15 mM K+. Arrhythmia susceptibility was reduced and onset delayed by raising the K+ concentration delivered to the adjacent coronary bed. Arrhythmogenesis could be replicated in five or more successive runs in a single heart, indicating a lack of preconditioning. Readmission of control K+ (washout of high K+) mimicked the effects of reperfusion by rapidly causing new episodes of ventricular arrhythmias. The concentration dependence of this effect was exponential, not bell shaped, with washout of 18 mM K+ most arrhythmogenic. There was no preconditioning phenomenon.
Regional hyperkalaemia and K+ washout are factors sufficient to account for arrhythmogenesis during ischaemia and reperfusion, respectively. The new model is suitable for assessment of whether these factors are also necessary for arrhythmogenesis (by equivalent evaluation of other putative arrhythmogens).
旨在开发一种新模型，以确定哪些与缺血和再灌注相关的因素足以引发心律失常，并使用该模型研究局部高钾血症和钾离子洗脱情况。
用含正常范围内钾离子（2、3、4或5 mM）的缓冲溶液灌注兔心脏（n = 150）。回旋支冠状动脉以相似速率用相似溶液独立灌注。使钾离子浓度局部升高，随后恢复至对照钾离子水平，以模拟缺血和再灌注期间钾离子的局部变化。
局部高钾血症（钾离子浓度 = 9、12、15或18 mM）在三个重要方面模拟了（浓度依赖性）局部缺血对心电图的已知影响，即引发室性心律失常、心电图形态的局部变化以及局部交替变化。心律失常与钾离子之间的关系呈钟形，在钾离子浓度为15 mM时易感性达到峰值。通过提高输送至相邻冠状动脉床的钾离子浓度，心律失常易感性降低且发作延迟。心律失常可在单个心脏中连续五次或更多次重复出现，表明不存在预处理现象。重新输入对照钾离子（洗脱高钾离子）通过迅速引发新的室性心律失常发作，模拟了再灌注的影响。这种影响的浓度依赖性是指数性的，而非钟形，洗脱18 mM钾离子时致心律失常性最强。不存在预处理现象。
局部高钾血症和钾离子洗脱分别是缺血和再灌注期间足以引发心律失常的因素。该新模型适用于评估这些因素对于心律失常发生是否也是必要的（通过对其他假定的致心律失常因素进行等效评估）。
