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John P. Wikswo, Ph.D.

Photo of John P. Wikswo, Ph.D.John P. Wikswo, Ph.D.
Gordon A. Cain University Professor, Vanderbilt University, Nashville, Tennessee
Correlative Multimodal Imaging of Cardiac Electrophysiology and Metabolism

Administered by the NHLBI Division of Cardiovascular Sciences, Heart Failure and Arrhythmia Branch
FY 2009 Recovery Act Funding: $566,138

Additional Funding:
Correlative Multimodal Imaging of Cardiac Electrophysiology and Metabolism
FY 2010 Recovery Act Funding
Administered by the NHLBI Division of Cardiovascular Sciences, Heart Failure and Arrhythmia Branch: $540,275
More information about the grant
Total funding: $1,106,413

October 30, 2009
Researchers Develop Innovative Imaging System to Study Sudden Cardiac Arrest

Research Focus: In the United States, 250,000 to 450,000 people die each year as a result of sudden cardiac arrest (SCA), a condition that is triggered by an abnormal heart rhythm, or arrhythmia. John Wikswo, Ph.D., and the research team at Vanderbilt University seek to reduce this public health burden.

During SCA, a complex series of electrical and metabolic events occur. Dr. Wikswo and his team are studying how these events relate to each other. "We are seeking to understand and control the metabolic abnormalities that underlie many cardiac electrical problems," said Dr. Wikswo, one of four principal investigators on the project. "We expect that what we learn will allow us to better understand how to prevent and treat life-threatening cardiac rhythm disturbances."

To accomplish this, the team will create and test an innovative way to visualize the electrical activity of the heart in relation to its structure and changing metabolic state. Their multimodal cardiac imaging technique will use a two-camera approach to integrate electrophysiological imaging with optical fluorescence imaging of metabolic activity associated with damaged heart tissue and tachycardia (accelerated heart rate). In addition, biochemical and electrochemical studies of heart tissue under controlled conditions will enhance the understanding of the relationship between metabolic changes and the heart's electrical activity.

"To date, many researchers have focused intensely on the subtleties of cardiac electrical activity," said Dr. Wikswo. "However, attempts to control or eliminate cardiac arrhythmias by drugs that modify the activity of ion channels responsible for development of the heart's electrical signal have proven disappointing because of the side effects."

Dr. Wikswo and his team are instead focusing on the metabolic changes involved in arrhythmias. "Drugs that affect heart metabolism without direct effects on its ion channels may have important benefits in restoring and maintaining normal electrical activity of the heart, especially after blood flow to the heart has been reduced," he said.

Economic Impact: The grant enables a 13-member research team to continue working on this research project, which would otherwise have been terminated because of the flat National Institutes of Health (NIH) budget, according to Dr. Wikswo. "Without these funds, we would have had to reduce substantially our activity in cardiac research," he said. "This would have impacted adversely a number of people working in the lab."

With the Recovery Act funding from the National Heart, Lung, and Blood Institute, the team also purchased a pair of $60,000 state-of-the-art high-speed digital cameras made in America to record the changes in the metabolic and electrical activity of isolated cardiac tissue under conditions associated with SCA. The cameras use a complementary metal-oxide semiconductor chip, developed in part through funding from the NIH's Small Business Innovation Research program.

An Interdisciplinary Approach: Two other principal investigators work with Dr. Wikswo at Vanderbilt: Veniamin Sidorov, Ph.D., described by Dr. Wikswo as "remarkably skilled in designing and conducting these challenging experiments and in analyzing the tremendous amount of data from our cameras;" and Franz Baudenbacher, Ph.D.,"the best person in the world at recording magnetic images of cardiac electrical activity and very experienced in multimodal cardiac imaging techniques ranging from single cells to whole hearts."

The group's collaborator at the Food and Drug Administration, Richard Gray, Ph.D., is an expert in cardiac measurements and models, as well as the quantitative analysis of cardiac activity images.

"My skill is in building instruments and designing experiments that bring together different technologies and disciplines," said Dr. Wikswo. "Together, we are providing a rather unique interdisciplinary approach to challenging problems in heart disease."

'A Strange Little Conference Room': "I am lucky that most of my time in the lab is spent doing science – primarily in the form of small group discussions about specific projects," said Dr. Wikswo. "Our conference room has four video projectors, allowing multiple people to share their computer screens with the whole group. We have four to 10 people in a room. It's like a design studio where you have a bunch of smart, creative people in the room looking at a problem from different angles; in our case, it's engineers, physicists, chemists, biologists, and physicians. This strange little conference room we have is really phenomenal – it's an extremely effective means of sharing information and developing new ideas."

An Inherited Curiosity: "My father was an industrial research chemist who could build anything, and my mother was a mathematics professor, so I was given ample opportunity to learn science, engineering, and math," said Dr. Wikswo. "I got my love for teaching from my mother, and I even gave my first hour-long lecture on binary arithmetic in one of her college algebra classes when I was in the 5th grade."

"Marvelous to Look At": Dr. Wikswo has been studying the heart since 1971. "The electrical activity of the heart is just marvelous to look at and try to figure out," he said. "I think there's a lot that can be done to improve the treatment of heart rhythm disorders. It's a very complicated problem.

"The American public is paying for this research," added Dr. Wikswo. "They deserve to get answers to their questions and their problems solved. Heart disease is still the number one killer in the United States, so these are important problems. I'm very appreciative of the support, and I'm happy to help solve these problems."

Written by Sheila Walsh

Last Updated:August 10, 2010

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