Artifacts, assumptions, and ambiguity: Pitfalls in comparing experimental results to numerical simulations when studying electrical stimulation of the heart

Abstract

Insidious experimental artifacts and invalid theoretical assumptions complicate the comparison of numerical predictions and observed data. Such difficulties are particularly troublesome when studying electrical stimulation of the heart. During unipolar stimulation of cardiac tissue, the artifacts include nonlinearity of membrane dyes, optical signals blocked by the stimulating electrode, averaging of optical signals with depth, lateral averaging of optical signals, limitations of the current source, and the use of excitation-contraction uncouplers. The assumptions involve electroporation, membrane models, electrode size, the perfusing bath, incorrect model parameters, the applicability of a continuum model, and tissue damage. Comparisons of theory and experiment during far-field stimulation are limited by many of these same factors, plus artifacts from plunge and epicardial recording electrodes and assumptions about the fiber angle at an insulating boundary. These pitfalls must be overcome in order to understand quantitatively how the heart responds to an electrical stimulus. (c) 2002 American Institute of Physics.

Examination of stimulation mechanism and strength-interval curve in cardiac tissue

“…Another discrepancy is the lower thresholds for resting tissue in Roth's simulations (0.038 mA for cathodal and 0.41 mA for anodal stimulation) compared with our experimental measurements [0.15 mA (SD 0.09; n ϭ 9) for cathodal and 1.05 mA (SD 0.36; n ϭ 11) for anodal stimulation]. The disparity in unipolar stimulation thresholds in numerical and experimental studies is well known and has been discussed in the literature, although a definitive explanation has not been determined (40). However, the anodal-cathodal threshold ratio for the theoretical data (factor of 10.8) is close to the ratio from our experiments (factor of 7.0).…”

Intracellular Calcium and the Mechanism of the Dip in the Anodal Strength-Interval Curve in Cardiac Tissue

“…This disparity in threshold is well known and has been discussed previously, although a satisfactory explanation has not been determined. 19 …”

Numerical Simulations of Cardiac Tissue Excitation and Pacing Using the Bidomain Model

“…The remaining discrepancies between theory and experiment have been explored in detail [48]. The anode break mechanism predicted by the bidomain model is quite different than the classical anode break mechanism that Hodgkin and Huxley studied in nerve axons [74].…”

“…When light is shined on the tissue, the resulting fluoresced light depends on the transmembrane potential, allowing the optical measurement of electrical behavior. The method has its weaknesses, which make comparing experimental data to theoretical predictions a challenge [48,49]. To understand one of the problems, we first analyze the three-dimensional distribution of transmembrane potential.…”