Reperfusion-induced arrhythmias in the isolated rabbit heart: characterization of the influence of the duration of regional ischemia and the extracellular potassium concentration.

The systematic investigation of the genesis and control of arrhythmias during ischemia and reperfusion requires a reproducible preparation in which arrhythmias can be induced with relative ease. The requirements for appropriate statistical analysis often requires that large numbers of animals be studied and hence cost becomes an important factor. The rat offers many advantages but is often criticized on the basis of its atypical action potential and a need exists for an alternative small animal model. The guinea-pig, because of its highly collateralized coronary circulation, cannot be used for the induction of regional ischemia and the rabbit is often dismissed on the grounds that it has a low incidence of arrhythmias. In the present study we have shown that if the perfusion conditions (duration of ischemia and extracellular potassium concentrations) are appropriately selected then the rabbit heart exhibits a high and reproducible susceptibility to reperfusion-induced arrhythmias. Hearts (n = 10 in each group) were subjected to 20 min of regional ischemia induced by coronary artery ligation, the potassium concentration of the perfusate being 2.50, 2.75, 3.00, 3.25, 3.50 or 4.38 mM. A bell-shaped relationship was demonstrated with an optimum susceptibility at 3.00 mM where 60% of the hearts exhibited reperfusion-induced ventricular fibrillation and 80% of the hearts exhibited ventricular tachycardia. With concentration of potassium above 3.00 mM there was a progressive decline in susceptibility (only one out of ten hearts fibrillated when potassium was 4.38 mM). With concentrations of potassium below 3.00 mM there was also a reduction in susceptibility to fibrillation. Using an optimally arrhythmogenic concentration of 3.00 mM potassium, hearts (n = 10 in each group) were subjected to 10, 15, 20, 25, 30 or 40 min of regional ischemia followed by 5 min reperfusion. A bell-shaped time-susceptibility curve was obtained such that with increasing durations of ischemia from 20 to 30 min there was an increasing incidence of reperfusion-induced arrhythmias. Beyond this optimum (at which 60% exhibited reperfusion-induced ventricular fibrillation) there was a decline in the susceptibility of the hearts to fibrillation. Heart rate and coronary flow exhibited no consistent significant relationship with either potassium concentration or duration of regional ischemia. Studies of the time of onset and duration of reperfusion-induced arrhythmias showed that 90% of arrhythmias were initiated within the first 60 s of reperfusion but that the duration was highly variable.(ABSTRACT TRUNCATED AT 400 WORDS)