Curtis M J, Hearse D J
Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
J Mol Cell Cardiol. 1989 Jan;21(1):21-40. doi: 10.1016/0022-2828(89)91490-9.
The effects of four different K+ concentrations (2, 4, 6 or 8 mM) on arrhythmias resulting from ischaemia, and from reperfusion (after 3, 5, 7, 10, 15 or 30 min of ischaemia), in isolated perfused rat hearts were examined. A randomized experimental design with blind analysis was used. Regional myocardial ischaemia was produced by occlusion of the left main coronary artery. The incidence of ischaemia-induced ventricular fibrillation (VF) was inhibited by elevating K+ concentration, as reported previously. Furthermore, this effect was linearly and inversely related to the log of the K+ concentration (r = 0.99, P less than 0.001), a finding which has not been reported previously. This finding implies that the antiarrhythmic effect may result from depolarization in the non-ischaemic tissue, since resting membrane potential is also linearly related to the log of the K+ concentration. The maintenance of ischaemia-induced VF (its tendency to sustain) was also influenced by K+, in that a significantly higher incidence of sustained VF (defined as VF still present at the end of the period of ischaemia) was seen with 2 mM K+ compared with higher K+ concentrations (P less than 0.05). In contrast with its effect on the incidence of ischaemia-induced VF, K+ was without effect on the incidence of reperfusion-induced VF, indicating that reperfusion initiates VF independently of the K+ concentration in the perfusion fluid. However, the maintenance of reperfusion-induced VF was K+-dependent (in a similar manner to the maintenance of ischaemia-induced VF). In summary, the effects of K+ on ischaemia-induced VF were different from its effects on reperfusion-induced VF. We conclude that ischaemia-induced VF and reperfusion-induced VF are unlikely to be initiated by a common electrophysiological mechanism since only the former was influenced by K+. The mechanisms of maintenance of ischaemia-induced VF and reperfusion-induced VF might, however, be common, since the tendency for spontaneous defibrillation to occur (as reflected by the incidence of sustained VF) was equally sensitive to K+ in both settings. Finally, the nature of the time course of susceptibility to ischaemia-induced VF compared with that of reperfusion-induced VF raises the possibility that the reperfusion-induced VF may be clinically relevant as a cause of sudden death only when ischaemia-induced VF is suppressed.
研究了四种不同钾离子浓度（2、4、6或8 mM）对离体灌注大鼠心脏缺血及再灌注（缺血3、5、7、10、15或30分钟后）所致心律失常的影响。采用随机实验设计并进行盲法分析。通过阻断左冠状动脉主干造成局部心肌缺血。如先前报道，升高钾离子浓度可抑制缺血诱导的心室颤动（VF）发生率。此外，这种效应与钾离子浓度的对数呈线性反比关系（r = 0.99，P < 0.001），这一发现此前未见报道。这一发现意味着抗心律失常作用可能源于非缺血组织的去极化，因为静息膜电位也与钾离子浓度的对数呈线性相关。钾离子对缺血诱导的VF的维持（其持续倾向）也有影响，即与较高钾离子浓度相比，2 mM钾离子时持续性VF（定义为缺血期末仍存在的VF）的发生率显著更高（P < 0.05）。与对缺血诱导的VF发生率的影响相反，钾离子对再灌注诱导的VF发生率无影响，表明再灌注引发VF与灌注液中的钾离子浓度无关。然而，再灌注诱导的VF的维持依赖于钾离子（与缺血诱导的VF的维持方式类似）。总之，钾离子对缺血诱导的VF的作用不同于其对再灌注诱导的VF的作用。我们得出结论，缺血诱导的VF和再灌注诱导的VF不太可能由共同的电生理机制引发，因为只有前者受钾离子影响。然而，缺血诱导的VF和再灌注诱导的VF的维持机制可能是共同的，因为在两种情况下，自发除颤发生的倾向（以持续性VF的发生率反映）对钾离子同样敏感。最后，与再灌注诱导的VF相比，缺血诱导的VF易感性的时间进程特点增加了一种可能性，即只有当缺血诱导的VF被抑制时，再灌注诱导的VF作为猝死原因在临床上才可能具有相关性。
