Nifedipine antagonizes ouabain-induced ST-segment changes and derangement of epicardial activation pattern in isolated rabbit hearts

Abstract

Isolated rabbit hearts, perfused according to the Langendorff technique were treated with 0.2 μmol/l ouabain or with a combination of 0.2 μmol/l ouabain and 3 nmol/l nifedipine. In a second series of experiments, a combination of 0.2 μmol/l ouabain with 0.2 μmol/l nitroglycerin was examined. Under this treatment, coronary flow and left ventricular pressure were continuously measured and, furthermore, the epicardial potential distribution was mapped with high temporal (4 kHz/channel) and spatial resolution (256 electrodes, arranged in 4 plates with 64 electrodes each, 8 × 8 matrix with 1 mm mesh size). Ouabain led to the expected positive inotropy of 10%, but also to a decrease in coronary flow of 15%. Besides these changes a nearly generalized ST-segment elevation could be observed. Moreover, the epicardial activation pattern was disturbed by changes in the location of epicardial breakthrough-points. Concomitantly, the epicardial activation vector field was deranged. Under the additional influence of nifedipine, coronary flow was reduced by only 5%, whereas the positive inotropic effect remained unchanged. The epicardial ST-elevation was diminished significantly and there was no derangement in the process of epicardial activation. Nitroglycerin led to an increase in relative coronary flow comparable to that observed under nifedipine but did not antagonize the disturbances of the process of activation by ouabain and only partially inhibited ST-elevation. Hence, it is concluded that ouabain already provokes coronary vasoconstriction in thereapeutic concentrations leading to ST-elevation and prearrhythmic changes in the process of excitation. These changes could be diminished by additional treatment with nifedipine, but not with nitroglycerin.