Category Archives: Article Reviews

Article Reviews

Wednesday Article Review: Unpinning of a Rotating Wave in Cardiac Muscle by an Electric Field

For the past few weeks, I’ve made Wednesday “Article Review” day. I’ll still post reviews that I deem pertinent on other days, but the goal is to post one each Wednesday at a minimum.

The Hubmed page for today’s article is here: Unpinning of a Rotating Wave in Cardiac Muscle by an Electric Field by Alain Pumir and Valentin Krinsky

Tachycardia (fast heart beat) is commonly caused by a rotating wave of activation in the heart. The study of rotating waves of this type has years of legacy in theoretical and chemical dynamics studies. Today’s article covers rotating waves pinned to anatomical obstacles such as valve openings in the heart. Rotating waves circle a core, which can be functional (a property of the wave shape and dynamics) or anatomical (an obstacle). In the case of an anatomical obstacle, the wave can be eliminated by ablation, which is commonly used in the atria, electrical defibrillation, or possibly unpinning / antitachycardia pacing (ATP). Ablation is typically invasive, requiring catheterization, and defibrillation requires an external shock, or surgery to implant an ICD. Defibrillation, either externally or internally, damages the heart, is painful, and often causes loss of consciousness. Antitachycardia pacing and electrical unpininning open the possibility of elimination of tachycardia with small shocks.

The principle of electrical unpinning, proposed by Huyet et al. (1998) and Krinsky et al. (1995), is that when a localized stimulus is applied in a certain part of the wave tail, it may move the core of the rotating wave. It’s difficult to place a stimulus in a particular place at a particular time in a patient’s heart, but it turns out that when an electrical field is applied over an obstacle, areas of depolarization (positive change) and hyperpolarization (negative change) manifest on the borders of the obstacle.

The paper by Pumir and Krinsky details how a small electrical field may be applied at a specific timing relative to wave rotation in order to create such a depolarization on an obstacle that will unpin a wave attached to that same obstacle. They used simplified models of cardiac action potentials, including the Beeler-Reuter and Fitzhugh models. Since the method deals with the dynamics of a spiral wave, and not with particulars of ionic currents, it’s a safe bet that the methods will apply in more complex models and cardiac tissue.

I won’t repeat the article’s simple and logical explanation of how it works — go read it. It’s only 9 pages, the figures are clear, and the math is mercifully simplified in a way that (ostensibly) doesn’t undermine the results.

Article Review: Role of ATP-Regulated Potassium Channels … [in] Ischemia by Furukawa et al.

Another long title. The whole thing is below.

Hubmed Page: Role of Cardiac ATP-Regulated Potassium Channels in Differential Responses of Endocardial and Epicardial Cells to Ischemia

This 8-page article quantifies in great detail the ATP sensitivity of ATP-regulated potassium channels, often referred to as IK(ATP). As the article shows by many references, it’s known that the epicardium of the heart is more sensitive to lack of oxygen (and therefore metabolic energy in the form of adenosine triphosophate — ATP) than then endocardium of the heart. The authors of this study first measured currents from ATP-regulated potassium channels in the presence of CN (cyanide, which blocks the generation of ATP), and then more directly pulled off patches of cell membrane with ATP-regulated potassium channels, and tested them in the presence of varying concentrations of ATP. In both cases, action potentials (the way in which cardiac cells ‘fire’ to initiate contraction and signal each other) were shortened more in the epicardial patches than in those from the endocardium. The degree to which this shortening occurred and at what concentrations is well-documented in the article.
The results of this study are clear, well-presented, and extremely useful in modeling ischemia in the heart. It’s a long read, with a ton of experimental detail, but the results are worth slogging through all of that. This fundamental article on ATP-regulated potassium channels is a must-read for anyone wanting to study ischemia and infarction in the heart.

Article Review: What can nonlinear dynamics teach us about … [tachycardia/fibrillation]? by Li et al.

I had to cut the title a bit short, because it’s a long one.

Hubmed Page: What can nonlinear dynamics teach us about the development of ventricular tachycardia/ventricular fibrillation?

This short article (3 pages) describes in a very readable way how nonlinear dynamics may be applied to understand beat-to-beat alternans of action potential duration and amplitude. While the actual methods used are not written, the concept is well-conveyed. I’ve not yet had a course in nonlinear dynamics, so some of the terminology was a bit beyond my understanding. I don’t know anything about eigenmodes, for example.

After providing a brief background of nonlinear dynamics, the authors elaborate on how they used nonlinear dynamics to develop a realistic model of calcium cycling and alternans in the canine myocardium. All-in-all, it’s not a terribly informative paper. Like many articles that mention fibrillation and tachycardia, it comes up short of actually linking the found mechanisms to clinical application and human disease. It is, however, a nice introduction to the topic, and the references look promising. If you have an interest in cardiac arrhythmias, and aren’t very familiar with this sort of analysis, I recommend you read it over and consider further study of the topic.

Article Review: Reentry in heterogeneous cardiac tissue described by the Luo-Rudy ventricular action potential model by K.H.W.J. Ten Tusscher and A.V. Panfilov

Hubmed Page: Reentry in heterogeneous cardiac tissue described by the Luo-Rudy ventricular action potential model (with abstract)
The primary focus of this article is the effect of a gradient of action potential duration (APD) on spiral wave dynamics. The authors ran several simulations of a spiral wave using the Luo-Rudy I ionic model, and tracked the drift of the spiral wave’s phase singularity with respect to a gradient of APD. As the abstract says, spiral wave drift was in the direction of longer rotation period (analogous to longer APD, in this case), which is right in line with what should be expected. Higher-frequency rotation should push the spiral wave center (phase singularity) away, regardless of the phenomenon underlying that higher frequency. The article is a medium-length read at six pages. While it seems somewhat redundant, in that every test yielded approximately the same results, this leant strong support to the conclusions of the paper — no caveats or qualifications were necessary. The conclusions of this article are important to the study of arrhythmias in regional disease, where gradients of electrophysiological disease exist along the borders between normal and diseased tissues.
The paper does not, unfortunately, delve into the details of why high-frequency rotation pushes away low-frequency rotation. A similar phenomenon was explained to me this past fall by Dr.Valentin Krinski with regard to two interacting spiral waves or periodic sources. I’m currently struggling to find the bridge — the relationship between different frequencies in different parts of the same spiral wave, and different frequencies in different spiral waves.

If you know why this is, kindly leave a comment. In the mean time I’ll be puzzling over it.