Rabbit ventricular myocardium undergoing simulated ischemia and reperfusion in a double compartment tissue bath: a model to investigate both antiarrhythmic and arrhythmogenic likelihood

An ischemia/reperfusion-simulating model in rabbit tissue should be right oriented and clinically relevant to provide a non expensive approach for manipulations of currents involved in the repolarization process. Standard right ventricular guinea-pig (N=18) and newly investigated rabbit (N=12) myocardial strips were placed in a special perfusion chamber allowing partition into two segments independently superfused with oxygenated Tyrode's solution or a modified Tyrode's solution mimicking ischemia by: 1) increased extracellular potassium concentration (12 mmol/L), 2) decreased HCO3 (-) concentration (9 mmol/L), leading to a decrease in pH (6.90 ± 0.05), 3) decreased pO2 by replacement of 95% O2 and 5% CO2 by 95% N2 and 5% CO2 gas mixture, and 4) complete withdrawal of glucose. There were significant differences in rabbit as compared to guinea-pig preparations in baseline (p<0.02) and post-ischemic-like (p<0.01) APA and RMP with lower values in the formers, and lower post-ischemic Vmax in rabbit preparations (25±15 versus 97±83 V/s, p<0.01) but neither baseline nor post-ischemic-like or absolute changes in APD50, APD90 were different. In ischemia- and reperfusion-like phases, there were high proportions of single spontaneous repetitive responses, both in guinea-pig (respectively 50 and 89%) and rabbit preparations (respectively 67 and 92%). Guinea-pig preparations showed higher incidence of severe spontaneous repetitive responses (61 versus 17%, p<0.02). This rabbit model is proposed to investigate both anti- and pro-arrhythmic effects of drugs acting at various levels electrophysiologically, which may be obtained with great power and relatively few (around 10 per group) preparations. This model should now be tested pharmacologically.