Theoretical Modeling and Experimental Detection of the Extracellular Phasic Impedance Modulation in Rabbit Hearts

Theoretical cardiac electrophysiology focuses on the dynamics of the membrane and sarcoplasmic reticulum ion currents; however, passive (e.g., membrane capacitance) and quasi-active (response to small signals) properties of the cardiac sarcolemma, which are quantified by impedance, are also important in determining the behavior of cardiac tissue. Theoretically, impedance varies in the different phases of a cardiac cycle. Our goal in this study was to numerically predict and experimentally validate these phasic changes. We calculated the expected impedance signal using analytic methods (for generic ionic models) and numerical computation (for a rabbit ventricular ionic model). Cardiac impedance is dependent on the phase of the action potential, with multiple deflections caused by a sequential activation and inactivation of various membrane channels. The two main channels shaping the impedance signal are the sodium channel causing a sharp and transient drop at the onset of action potential and the inward rectifying potassium channel causing an increase in impedance during the plateau phase. This dip and dome pattern was confirmed in an ex-vivo rabbit heart model using high-frequency sampling through a monophasic action potential electrode. The hearts were immobilized using a myosin-inhibitor to minimize motion artifacts. We observed phasic impedance changes in three out of four hearts with a dome amplitude of 2 - 4Ω. Measurement of phasic impedance modulation using an extracellular electrode is feasible and provides a non-invasive way to gain insight into the state of cardiac cells and membrane ionic channels. The observed impedance recordings are consistent with the dip and dome pattern predicted analytically.