Ischaemia-induced and reperfusion-induced arrhythmias differ in their sensitivity to potassium: implications for mechanisms of initiation and maintenance of ventricular fibrillation.

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.