The Bidomain Model of Cardiac Tissue: Predictions and Experimental Verification
In the early 1990s, I was asked to write a chapter for a book titled Neural Engineering. My chapter had nothing to do with nerves, but instead was about cardiac tissue analyzed with the bidomain model. (You can learn more about the bidomain model in Chapter 7 of Intermediate Physics for Medicine and Biology.)
“The Bidomain Model of Cardiac Tissue: Predictions and Experimental Verification” was submitted to the editors in January, 1993. Alas, the book was never published. However, I still have a copy of the chapter, and you can download it here. Now-after nearly thirty years-it’s obsolete, but provides a glimpse into the pressing issues of that time.
I was a impudent young buck back in those days. Three times in the chapter I recast the arguments of other scientists (my competitors) as syllogisms. Then, I asserted that their premise was false, so their conclusion was invalid (I’m sure this endeared me to them). All three syllogisms dealt with whether or not cardiac tissue could be treated as a continuous tissue, as opposed to a discrete collection of cells.
The Spach Experiment
Continuous cable theory predicts that the time course of the action potential does not depend on differences in axial resistance with direction.
The rate of rise of the cardiac wave front is observed experimentally to depend on the direction of propagation.
Therefore, cardiac tissue does not behave like a continuous tissue.
I then argued that their first premise is incorrect. In one-dimensional cable theory, the time course of the action potential doesn’t depend on axial resistance, as Spach claimed. But in a three-dimensional slab of tissue superfused by a bath, the time course of the action potential depends on the direction of propagation. Therefore, I contended, their conclusion didn’t hold; their experiment did not prove that cardiac tissue isn’t continuous. To this day the issue is unresolved.
A second example considered the question of defibrillation. When a large shock is applied to the heart, can its response be predicted using a continuous model, or are discrete effects essential for describing the behavior?
An applied current depolarizes or hyperpolarizes the membrane only in a small region near the ends of a continuous fiber.
For successful defibrillation, a large fraction of the heart must be influenced by the stimulus.
Therefore, defibrillation cannot be explained by a continuous model.
I argued that the problem is again with the first premise, which is true for tissue having “equal anisotropy ratios” (the same ratio of conductivity parallel and perpendicular to the fibers, in both the intracellular and extracellular spaces), but is not true for “unequal anisotropy ratios.” (Homework Problem 50 in Chapter 7 of IPMB examines unequal anisotropy ratios in more detail). If the premise is false, the conclusion is not proven. This issue is not definitively resolved even today, although the sophisticated simulations of realistically shaped hearts with their curving fiber geometry, performed by Natalia Trayanova and others, suggest that I was right.
The final example deals with the induction of reentry by successive stimulation through a point electrode. As usual, I condensed the existing dogma to a syllogism.
In a continuous tissue, the anisotropy can be removed by a coordinate transformation, so reentry caused by successive stimulation through a single point electrode cannot occur, since there is no mechanism to break the directional symmetry.
Reentry has been produced experimentally by successive stimulation through a single point electrode.
Therefore, cardiac tissue is not continuous.
Once again, that pesky first premise is the problem. In tissue with equal anisotropy ratios you can remove anisotropy by a coordinate transformation, so reentry is impossible. However, if the tissue has unequal anisotropy ratios the symmetry is broken, and reentry is possible. Therefore, you can’t conclude that the observed induction of reentry by successive stimulation through a point electrode implies the tissue is discrete.
I always liked this book chapter, in part because of the syllogisms, in part because of its emphasis on predictions and experiments, but mainly because it provides a devastating counterargument to claims that cardiac tissue acts discretely. Although it was never published, I did send preprints around to some of my friends, and the chapter took on a life of its own. This unpublished manuscript has been cited 13 times!
Trayanova N, Pilkington T (1992) “The use of spectral methods in bidomain studies,” Critical Reviews in Biomedical Engineering, Volume 20, Pages 255–277.
Winfree AT (1993) “How does ventricular tachycardia turn into fibrillation?” In: Borgreffe M, Breithardt G, Shenasa M (eds), Cardiac Mapping, Mt. Kisco NY, Futura, Chapter 41, Pages 655–680.
Henriquez CS (1993) “Simulating the electrical behavior of cardiac tissue using thebidomain model,” Critical Reviews of Biomedical Engineering, Volume 21, Pages 1–77.
Wikswo JP (1994) “The complexities of cardiac cables: Virtual electrode effects,” Biophysical Journal, Volume 66, Pages 551–553.
Winfree AT (1994) “Puzzles about excitable media and sudden death,” Lecture Notes in Biomathematics, Volume 100, Pages 139–150.
Roth BJ (1994) “Mechanisms for electrical stimulation of excitable tissue,” Critical Reviews in Biomedical Engineering, Volume 22, Pages 253–305.
Roth BJ (1995) “A mathematical model of make and break electrical stimulation ofcardiac tissue by a unipolar anode or cathode,” IEEE Transactions on Biomedical Engineering, Volume 42, Pages 1174–1184.
Wikswo JP Jr, Lin S-F, Abbas RA (1995) “Virtual electrodes in cardiac tissue: A common mechanism for anodal and cathodal stimulation,” Biophysical Journal, Volume 69, Pages 2195–2210.
Roth BJ, Wikswo JP Jr (1996) “The effect of externally applied electrical fields on myocardial tissue,” Proceedings of the IEEE, Volume 84, Pages 379–391.
Goode PV, Nagle HT (1996) “On-line control of propagating cardiac wavefronts,” The 18th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Amsterdam.
Winfree AT (1997) “Rotors, fibrillation, and dimensionality,” In: Holden AV, Panfilov AV (eds), Computational Biology of the Heart, Chichester, Wiley, Pages 101–135.
Winfree AT (1997) “Heart muscle as a reaction-diffusion medium: The roles of electric potential diffusion, activation front curvature, and anisotropy,” International Journal of Bifurcation and Chaos, Volume 7, Pages 487–526.
Winfree AT (1998) “A spatial scale factor for electrophysiological models of myocardium,” Progress in Biophysics and Molecular Biology, Volume 69, Pages 185–203.
I’ll end with the closing paragraph of the chapter.
The bidomain model ignores the discrete nature of cardiac cells, representing the tissue as a continuum instead. Experimental evidence is often cited to support the hypothesis that the discrete nature of the cells plays a key role in cardiac electrophysiology. In each case, the bidomain model offers an alternative explanation for the phenomena. It seems wise at this point to reconsider the evidence that indicates the significance of discrete effects in healthy cardiac tissue. The continuous bidomain model explains the data, recorded by Spach and his colleagues, showing different rates of rise during propagation parallel and perpendicular to the fibers, anodal stimulation, arrhythmia development by successive stimulation from a point source, and possibly defibrillation. Of course, these alternative explanations do not imply that discrete effects are not responsible for these phenomena, but only that two possible mechanisms exist rather than one. Experiments must be found that differentiate unambiguously between alternative models. In addition, discrete junctional resistance must be incorporated into the bidomain model. Only when such experiments are performed and the models are further developed will we be able to say with any certainty that cardiac tissue can be described as a continuum.
Originally published at http://hobbieroth.blogspot.com.