The potential of epicardial activation mapping in isolated hearts for the assessment of arrhythmogenic and antiarrhythmic drug activity

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In isolated rabbit hearts perfused according to the Langendorff technique, the pathway and time course of the epicardial activation process were studied by means of computer-assisted epicardial potential mapping, using a matrix of 256 unipolar AgCl electrodes (1 mm spatial and 0.25 msec temporal resolution). Activation time of each electrode was calculated (point of time of fastest negative intrinsic deflection). From the activation times of the surrounding electrodes, the direction and velocity of activation for each electrode were calculated, thereby allowing construction of an epicardial vector field. Furthermore, breakthrough points (BTPs) were determined as the earliest activated electrodes in agiven region. Vector-field orientation and BTP localization were compared under different conditions during perfusion with Tyrode's solution or during drug treatment. Thereby, we determined the similarity of the vector fields (two vectors were considered to be identical if not differing by more than 5°) and the percentage of BTPs with changed localization, referred to the total number of BTPs. For verification of the method we treated the hearts with ouabain (0.2 μmol l ) and observed progressive decline in vector-field similarity from 32% down to 14%, resulting in arrhythmia. Concomitantly, the percentage of BTPs with identical localization decreased from 81% to 50%. These changes could be reversed by additive treatment with 10 nmol 1 verapamil. From these results we conclude that arrhythmia is preceded by a state of deteriorated epicardial activation pattern (prearrhythmia), which can be quantitatively evaluated and used for detection of preventive antiarrhythmic drug action.