The rabbit dual coronary perfusion model: a new method for assessing the pathological relevance of individual products of the ischaemic milieu: role of potassium in arrhythmogenesis

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Abstract
Study objective — 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 hyperkalemia 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. Measurements and main results — Regional hyperkalemia (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 depend ence of this effect was exponential, not bell shaped, with washout of 18 mM K+ most arrhythmogenic. There was no preconditioning phenomenon. Conclusions — Regional hyperkalemia 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).

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