This study was designed to test the feasibility of using sinusoidal approximation in combination with a new instrumentation approach to resolve complex impedance (uCI) spectra from heart preparations. To assess that feasibility, we applied stimuli in the 10-4000 Hz range and recorded potential differences (uPDs) in a four-electrode configuration that allowed identification of probe constants (Kp) during calibration that were in turn used to measure total tissue resistivity ρt from rabbit ventricular epicardium. Simultaneous acquisition of a signal proportional to the supplied current (Vstim) with uPD allowed identification of the V-I ratio needed for ρt measurement, as well as the phase shift from Vstim to uPD needed for uCI spectra resolution. Performance with components integrated to reduce noise in cardiac electrophysiologic experiments, in particular, and provide accurate electrometer-based measurements, in general, was first characterized in tests using passive loads. Load tests showed accurate uCI recovery with mean uPD SNRs between 10-1 and 10-3 measured with supplied currents as low as 10 nA. Comparable performance characteristics were identified during calibration of nine arrays built with 250 μm Ag/AgCl electrodes, with uCIs that matched analytic predictions and no apparent effect of frequency (F = 0.12, P = 0.99). The potential ability of parasitic capacitance in the presence of the electrode-electrolyte interface associated with the small sensors to influence the uCI spectra was therefore limited by the instrumentation. Resolution of uCI spectra in rabbit ventricle allowed measurement of ρt = 134 ± 53 Ω cm. The rapid identification available with this strategy provides an opportunity for new interpretations of the uCI spectra to improve quantification of disease-, region-, tissue-, and species-dependent intercellular uncoupling in hearts. © 1964-2012 IEEE.