by Kelly C. Lockhart
Pacemakers are implanted in diseased hearts every day to electrically and artificially trigger heartbeats. Much more powerful defibrillators are also implanted to automatically calm the chaotic electrical activity of a heart that's contracting rapidly and erratically.
But scientists have never completely understood what happens to the heart when a strong electrical current from a pacemaker or defibrillator is used to "jump-start" it.
The recent discovery by a team of Vanderbilt physicists of what actually happens to the heart during strong electrical stimulation may lead to improved pacemakers and defibrillators, says team leaders John Wikswo, A.B. Learned Professor of Living State Physics, and Brad Roth, Robert T. Lagemann Assistant Professor of Living State Physics. A report of their study appears in the December 1995 issues of the IEEE Transactions of Biomedical Engineering and the Biophysical Journal.
More than 25 years ago, the Dutch physician Egbart Dekker reported four distinct modes by which an electrical stimulus could excite the heart: cathode make (the turning on of negative current), anode make (the turning on of positive current), cathode break (the turning off of negative current) and anode break (the turning off of positive current).
"One of the great puzzles of cardiac electrophysiology is why these four modes exist and how they work," Wikswo explained. "We now have solved the puzzle."
The missing puzzle piece was a correct computer model. The formulas used in previous computer models could only explain what happens when negative current was turned on. While at the National Institutes of Health, Roth used a more complicated mathematical model called the unequal-anisotropy bidomain model to study electrical stimulation of heart tissue. Using computer simulations, he found that his complex, nonlinear model could explain all four types of electrical stimulation.
Using hearts from anesthetized rabbits, Wikswo and his Vanderbilt colleagues Marc Lin and Rashi Abbas were able to verify Roth's predictions in their laboratory. The researchers mapped electrical activity in the heart with unprecedented spatial resolution by using a voltage-sensitive fluorescent dye and an optical system consisting of a laser and a high speed digital camera developed by Lin. In addition to confirming Roth's mathematical model, their results were fully consistent with Dekker's revelations and substantiated previous experiments at Vanderbilt, published in 1991.
Wikswo uses the analogy of a rock being thrown into a pond to explain the observed phenomena. The rock is the electrical stimulation and the pond is the heart tissue.
People expect that when a rock is thrown into a pond, water waves spread outwardly from the point where the rock hits the water. Similarly, for years scientists thought that when the heart is stimulated by an electrode, waves of electrical activity propagate outwardly in circles or ellipses from the stimulation site. The startling discovery by Wikswo and Roth was that if you look near the electrode, the waves of electrical activity have quite strange and complicated shapes, depending on the type of current and whether it is being turned on or off. It is as if throwing a rock into a pond would cause the water waves to propagate in the shape of a dog bone instead of a circle, or travel in some directions but not others, or start from a position different than where the rock struck the water.
Wikswo and Roth have shown that in the heart, the starting point and the direction of propagation of the waves differ greatly between the four kinds of electrical stimulation described by Dekker.
The result when a negative current is turned on is the easiest to understand. Stimulate with a small current and waves propagate outward. Increase the current's strength and waves begin farther from the electrode. Just like throwing a small rock or a big rock into a pond. The surprise was that the waves near the electrode for a strong current were dog-bone shaped, not elliptical.
"That's one strange rock," Wikswo said.
The result when positive current is turned on is even stranger: the waves start from some distance on either side of the electrode, instead of directly beneath it.
But the results when the heart is stimulated by turning off a current known as break stimulation are the strangest of all. When a long stimulus pulse is on, it resets parts of the heart. These regions will then allow waves to pass through them. But the same stimulus pulse also inhibits other parts of the heart. Waves can't pass through these regions. When the stimulus pulse ends, positive charge in the inhibited regions diffuses into the reset regions, initiating waves.
"During break stimulation, the stimulus pulse creates reset and inhibited regions," Roth explained. "It is when the pulse ends that propagating waves begin."
The locations of the active and inhibited regions change if the stimulus current is positive or negative, so break stimulation results in waves going in different directions.
When asked how it feels to solve a long-standing puzzle, Wikswo replied, "It's neat, particularly since most people thought unequal anisotropies were an unnecessary mathematical complication. In this case, nature wins once again with a complicated mechanism providing an elegantly simple and unifying explanation for a whole raft of phenomena."
The Vanderbilt studies were funded by the National Institutes of Health, the Tennessee Affiliate of the American Heart Association and the Whitaker Foundation.
Posted 1/29/96 at 10:00 a.m.