Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation

We analyzed central interstitial potential differences during multisite stimulation to assess the feasibility of using those recordings to measure cardiac microimpedances in multidimensional preparations. Because interstitial current injected and removed using electrodes with different proximities allows modulation of the portion of current crossing the membrane, we hypothesized that multisite interstitial stimulation would give rise to central interstitial potential differences that depend on intracellular and interstitial microimpedances, allowing measurement of those microimpedances. Simulations of multisite stimulation with fine and wide spacing in two-dimensional models that included dynamic membrane equations for guinea pig ventricular myocytes were performed to generate test data (∂φo). Isotropic interstitial and intracellular microimpedances were prescribed for one set of simulations, and anisotropic microimpedances with unequal ratios (intracellular to interstitial) along and across fibers were prescribed for another set of simulations. Microimpedance measurements were then obtained by making statistical comparisons between ∂φo values and interstitial potential differences from passive bidomain simulations (Δφo) in which a wide range of possible microimpedances were considered. Possible microimpedances were selected at 25% increments. After demonstrating the effectiveness of the overall method with microimpedance measurements using one-dimensional test data, we showed microimpedance measurements within 25% of prescribed values in isotropic and anisotropic models. Our findings suggest that development of microfabricated devices to implement the procedure would facilitate routine measurement as a component of cardiac electrophysiological study.

Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation

This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 μm) and wide (400 μm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discrete myoplasmic and gap-junctional components were prescribed intracellularly in later simulations. With constant microimpedances, multisite stimulation using 29 total electrode combinations allowed interstitial and intracellular microimpedance measurements at errors of 0.30% and 0.34%, respectively, with errors of 0.05% and 0.40% achieved using 6 combinations and 10 total electrodes. With discrete myoplasmic and junctional components, comparable accuracy was maintained following adjustments to the junctions to reflect uncoupling. This allowed uncoupling to be quantified as relative increases in total junctional resistance. Our findings suggest development of microfabricated devices to implement the procedure would facilitate routine measurement as a component of cardiac electrophysiological study.