ADVANCING THE FRONTS OF CARDIAC RESEARCH
Researchers combine electrostatic analysis and laboratory experiments to improve technology for arrhythmia treatment

By: Tamara C. Baynham, Stephen B. Knisley

This view of a rabbit heart shows the directions of fibers on the surface over which electric current flows. Regular electric impulses across this surface are vital to maintaining a healthy, functioning heart. Arrhythmias, which afflict 4.3 million Americans, result when electric impulses become abnormal and cause the heart to pump blood less effectively.

September 4, 1998, Pittsburgh, Pennsylvania - If you've ever listened through a stethoscope to a healthy human heart, you've probably heard its soft, rhythmic beating. However, for about 4.3 million Americans who experience arrhythmias, their heartbeats may be anything but rhythmic, they may even be life threatening.

Arrhythmias are abnormal rhythms of the heart that cause it to pump less effectively. Arrhythmias factor into half of all sudden cardiac deaths in the United States each year. Increased demand for improved technology for arrhythmia treatment and prevention, especially electronic implantable devices that apply an electric shock to the heart, is fueling research at the Cardiac Rhythm Management Laboratory in the Department of Biomedical Engineering at The University of Alabama at Birmingham.

Through laboratory testing on rabbit hearts and finite element models analyzed with software from Pittsburgh, PA-based Algor, Inc., the researchers have learned how the structure of heart fibers may affect the application and distribution of an electric current. The findings of this research will be applied to improve existing implantable devices to better regulate heart rhythms.

The Beating Heart
A normal healthy heart is about the size of an orange and pumps thousands of gallons of blood each day through the arteries, veins and capillaries of the circulatory system. The circulating blood replenishes all parts of the body with oxygen and nutrients and removes waste from cells.

The four chambers of the heart, the upper left and right atria and the lower left and right ventricles, must work in precise order. A specialized group of cells, called the sinus node, is located in the right atrium and sends electric impulses at a regular interval through heart fibers of the atria and ventricles. As the electric impulse propagates and moves uniformly through the fibrous membrane of the heart, the heart contracts to pump blood and then expands as the signal passes. Throughout this contraction/expansion cycle, the heart exhibits changes in the amount of current or voltage across its fibers, called transmembrane voltage.

For the heart to function normally, the distribution of the transmembrane voltage must be approximately uniform throughout the heart. If the values differ greatly, arrhythmia can occur because the electric impulses of the heart become disorganized. Heart disease or blocked arteries are often to blame for this disorganization. For example, if a main artery becomes blocked, blood flow is stopped to part of the heart. The heart loses its synchrony because all parts of the heart no longer function properly and arrhythmia occurs. Arrhythmias can cause the heart to beat either slower or faster than the normal rate of 60 to 100 beats per minute. This situation can lead to a potentially fatal condition called ventricular fibrillation where the heart quivers rapidly instead of pumping blood. If left untreated, the patient could die within minutes.

Treatments for Arrhythmia
Treatments vary for each type of arrhythmia. Excessive slowing of the heart often requires the implantation of an electronic pacemaker under the skin. Arrhythmias that result in an accelerated heart rate can be classified as either atrial or ventricular fibrillation. According to the American Heart Association, atrial fibrillation causes about 15 percent of strokes per year when blood clots develop in the atria and move to an artery in the brain. This type of fibrillation is often treated with medication to prevent clotting.

Ventricular fibrillation, the most serious type of fibrillation, is involved in a large number of the 250,000 sudden cardiac deaths in the United States each year. Ventricular fibrillation must be corrected immediately with electric shock therapy. The restored cardiac rhythm is maintained with medication or an electronic device called an automatic implantable cardioverter/defibrillator (AICD).

In recent years, more physicians have chosen AICDs to prevent death from fibrillation as studies have proven their effectiveness to be equal to or better than medications. Furthermore, not all patients who survive fibrillation can be effectively treated by drug therapy. Because fibrillation occurs across all age groups, these devices provide an alternative to lifelong medication and can improve the overall quality of life.

Common AICDs consist of batteries and a pulse generator insulated in a flat case, which is inserted under the skin. Insulated metal wires run from the case through veins to the heart cavity where electrodes are positioned directly within the heart. Sensor electrodes automatically detect when the heart is out of rhythm and signal the pulse generator to send an electric current through an exposed electrode. Therefore, fibrillation is halted quickly after irregular rhythms are detected.

Arrhythmias can be prevented with automatic implantable cardioverter/defibrillators (AICD), such as the Ventak (TM) AICD from Guidant Corporation Cardiac Pacemakers, Inc., St. Paul, Minnesota. Researchers at the Cardiac Rhythm Management Laboratory in the Department of Biomedical Engineering at The University of Alabama at Birmingham hope to apply their research findings to improving the effectiveness of these devices.

New Research to Improve Current Technology
Researchers at the Cardiac Rhythm Management Laboratory are working to improve current AICD technology by exploring better options for the most effective shapes and positions of electrodes on heart fibers as well as learning more about the fiber structure of the heart. Researchers employed Algor's electrostatic finite element analysis (FEA) software to study the distribution of an electric current as it flows through the heart. The researchers hoped to develop techniques that would create a more uniform change in membrane voltage to more efficiently halt ventricular fibrillation.

Current AICDs contain electrodes that are essentially small cylinders or the rounded tips of wire leads. Experiments to study how an electric current affects the heart have been performed with these small electrodes, called point electrodes. Point electrodes emit electric current, which spreads radially from the source much like ripples of water that result when a pebble is dropped into a pond. However, unlike the smooth surface of a pond, the fibers of the heart can create resistance to the current causing an uneven spread of current and a very non-uniform distribution of transmembrane voltage.

Because of the shape of a point electrode, it cannot be oriented with respect to the direction of the fibers to reduce resistance. The researchers hypothesized that, by using a longer line electrode instead of just a point, an electrode can be positioned either parallel or perpendicular to heart fibers to best transfer current and create a more uniform distribution of transmembrane voltage. A line electrode can be a series of points adjacent to each other to form a line or an entire segment of exposed wire applied directly to the heart.

Before the researchers could test this hypothesis, they needed to determine the density or distribution of the electric current emitted from a line electrode. Up to this point, classical electrodynamic theory had only been applied to conventional shapes, such as the disk-shaped electrode with radial symmetry. From the classical theory, researchers knew that more current is emitted from the edge of a disk than from the center. The researchers used Algor's electrostatic analysis software to determine how much current would be emitted from each point on the line. It was possible that more current could have been distributed from the ends of the electrode than from the middle segment.

The Finite Element Model
The researchers used Algor's Superdraw III, a precision finite element model-building tool, to model a 100 by 100-cm sheet, which represented a conductive area of the heart. They applied a resistivity value based on a thickness of 1 cm to simulate a uniform resistance over heart fibers. A 3.6 by 3.6-cm central region contained a 1-cm long electrode in the center. Voltage boundary elements were applied to points on the sheet that were in contact with the electrode.

Smaller two-dimensional planar elements were used around the electrode to achieve more detailed results in this area of concern and larger elements were used for outlying areas. Researchers specified that a voltage of 100 volts be applied at the electrode and that the voltage would be zero at the perimeter of the sheet. They found that the values chosen for the voltage and resistivity values affected the total current values, but did not affect how the current was distributed along the electrode.

Researchers used design and analysis software from Pittsburgh, PA-based Algor, Inc. to model and analyze the current distribution across heart fibers. This model shows electric current dissipating over a conductive sheet that corresponds to the surface of the heart. The inset shows the voltage across a 3.6 by 3.6-cm central region containing a line electrode.

The finite element model showed that current through the element faces at the ends of the electrodes was 151 percent larger than current near the electrode center. The researchers ran another electrostatic analysis to determine if the same effect would occur with a coarser mesh. These results indicated only a 113 percent increase near the electrode ends compared to the electrode center. This agrees with theory where the increase at ends is greater with a finer mesh and smaller with a coarser mesh. The researchers were able to show that the ends of a line electrode emit a higher concentration of current -- similar to that previously known for the edge of a disk electrode.

The researchers also used FEA to determine that the length of the line electrode does not affect the current distribution. Another finite element model was constructed with a 3 mm-long electrode located at the center. The analysis results indicated that the percentage of current coming from regions near the electrode ends made up about 50 percent of the total current regardless of electrode length.

This model shows the distribution of total electric current in the central area near the line electrode. Current through the element faces at the ends of the electrodes was larger than that near the electrode center.

Confirming FEA with Laboratory Testing
To confirm the results of the analysis and further test the positioning of the electrode with respect to heart fibers, the researchers applied line electrodes in varying positions and orientations on 13 hearts from New Zealand rabbits. The researchers used line electrodes comprised of a series of points applied adjacent to each other since the sum of the current from all points would correspond to current from a line. Rabbit hearts were chosen because their fibrous structure is similar to human hearts. Furthermore, they are smaller in size, comparable to that of a small peach. Smaller hearts are more feasible to study because of the small amount of artificial blood needed to keep them "alive."

The researchers began by applying line electrodes parallel to heart fibers to determine if the changes in transmembrane voltage of the fibers would become more uniform, as was hypothesized. As described previously, producing an efficient change of voltage from very irregular to uniform is vital to restoring regular heart rhythms.

The magnitude of changes in transmembrane voltage on either side of the electrode remained constant or increased in the central region for the first few millimeters away from the electrode and then began to decrease. The most significant changes in magnitude of transmembrane voltage occurred at the electrode ends. This finding correlates with the results of the electrostatic analysis, which showed a high concentration of current distribution in this area. A region near the center of the electrode experienced a negligible change in transmembrane voltage. The changes in transmembrane voltage had the same sign (i.e., were more uniform) when the line electrodes were parallel to heart fibers.

When researchers applied the line electrode parallel to the direction of the heart fibers, the change in transmembrane voltage across the fibers was more uniform, as indicated by the large blue area. Orange areas indicate areas of zero change. A more uniform change in voltage keeps the heart stable and at low risk for arrhythmia.   The line electrode aligned perpendicular to fibers resulted in a less uniform change in transmembrane voltage. Thin strips of orange indicate no change while the large pockets of red on both sides of the electrode indicate an adverse change, opposite of that needed for the transmembrane voltage to become uniform across the heart. These findings show that by orienting line electrodes parallel to heart fibers, physicians may be able to treat and prevent arrhythmias more efficiently and effectively than previous practices.

Next, the researchers oriented the line electrode perpendicular to heart fibers. The results indicated that the change in transmembrane voltage was less uniform across the fibers. Notably, the change in transmembrane voltage had different signs. Regions of small changes in voltage were detected 4 mm away from and on either side of the approximate center of the electrode.

Applications for Line Electrode Research
The research showed that the parallel orientation of a line electrode to heart fibers enhances the uniformity of the change in transmembrane voltage. Therefore, the application of a line electrode, instead of a point electrode, parallel to fibers enables better control over the distribution of the responses by the fibers to the application of electric current. This means that the change in transmembrane voltage would be more uniform and homogenous, closer to that of a normally functioning heart. This knowledge could be applied to future types of AICDs to regionally block the areas of the heart from becoming out of synch and prone to fibrillation.

Furthermore, line electrodes may play an important role in developing new, less invasive therapies for arrhythmias. This includes inserting line electrodes in the heart through the cardiac veins for therapeutic treatment. This method may increase the efficiency with which electric current is applied to the heart by distributing current from several electrodes. Furthermore, it is less traumatic than some previous methods used that required surgical procedures to open the chest.

Finally, the researchers were able to determine the distribution of the change in transmembrane voltage from a line electrode, made up of a summation of points, using electrostatic analysis. In the future, electrodes of other shapes can be studied using FEA to determine potential advantages of new types of electrode configuration.

With the prevalence of heart disease, arrhythmias and sudden death due to heart problems, it is important to learn more about the structure of the heart and its responsiveness to both electric current therapies and medications. This knowledge will help arrhythmia victims, both young and old, live longer and have more productive lives.

This research was supported by the National Institutes of Health Grant HL52003 and American Heart Association Grants AL 950032 and 9740173N. Ms. Baynham is a Ph.D. student in the Department of Biomedical Engineering at The University of Alabama at Birmingham. Her research interests include electrical stimulation and arrhythmia research. Dr. Knisley is an Established Investigator Awardee of the American Heart Association.