The National Institutes of Health recently awarded a $1.5 million grant to researchers Vadim V. Fedorov, Cynthia A. Carnes and Peter Mohler to find improved therapies to treat problems with the sinus node. This small tissue made of approximately 1,000 cells acts like the brain of the heart, controlling when and how it beats.
Currently, the standard of care includes an electronic pacemaker to regulate the heart rate. While the device works well for the approximately 3 million people who have one, there are drawbacks.
"Implanting a pacemaker is the necessary remedy at this time, but really it's a crutch," said Fedorov, a researcher in Ohio State'sDepartment of Physiology and Cell Biology. "The lack of understanding of the human pacemaker system, the sinoatrial node (SAN), and its complexity remains a critical barrier to treating heart rhythm disorders. The SAN knows when to beat faster during exercise or slower during sleep, but an electronic pacemaker beats steadily. With this grant award, we seek to restore and heal the SAN, rather than rely on pacemakers as the remedy," Fedorov said.
Before they can begin healing the SAN, the three co-investigators say they must first know how, why and where the SAN is failing. They hypothesize that SAN dysfunction may result from an increased sensitivity to adenosine, a metabolite that lowers the heart rate and conductivity in the heart. The team is first working to block the adenosine receptor to test the theory that heart failure results from adenosine-dependent signaling in the SAN.
A breakthrough in this research came through partnership with The Ohio State University Wexner Medical Center's Comprehensive Transplant Center, which provides damaged human hearts from consenting transplant cases.
"This is the goal of translational research. We're now able to study damaged human hearts, something that was just a dream five years ago," said Peter Mohler, director of the Dorothy M. Davis Heart and Lung Research Institute. "To solve the disease, you really need the right source of tissue, and we're one of only a few groups in the world that can study sinus node disease in human hearts, beyond simply mice and molecules."
Combined with this unique access, the team is using customized, advanced technology designed by Fedorov - a system of 3D high-resolution near-infrared optical mapping - to give them the enhanced images they need.
Carnes, a professor in Ohio State's College of Pharmacy, adds that it's Ohio State's unique ability to collaborate across multiple colleges and the Wexner Medical Center that has afforded this opportunity.
"We've built a first-class operation with bench-to-bedside research in arrhythmias at Ohio State," Carnes said. "Teamwork is integral to everything we do and this research project is a great example of that."
Fedorov, Carnes, and Mohler agree it may be years before they can turn their research toward therapies to heal the SAN, including new drug development or perhaps localized stem cell therapy.
More than 2 million Americans have sinoatrial node issues, which can be congenital or develop with age.
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