The research, published in the journal Circulation
, shows, compared to the left atrium, the right atrium of the human heart is three times more sensitive to adenosine. This biochemical plays a role in energy transfer among cells. It’s often produced during times of metabolic stress, such as after a heart attack or coronary artery bypass surgery, or during heart failure. When there is too much adenosine, it can provoke atrial fibrillation (AF).
“We’ve known that adenosine-induced AF sources may be located more frequently on the right side versus the left, but until now, it wasn’t clear what kinds of sources are there and what caused them on a molecular level,” said Vadim Fedorov
, an associate professor in the Department of Physiology and Cell Biology. “Now, we can see there is adenosine hypersensitivity in the right atrium.”
Fedorov and his multidisciplinary team, including cardiac surgeons and electrophysiologists at The Ohio State University Ross Heart Hospital, tested a hypothesis that adenosine-induced AF is maintained by reentrant drivers, which are rotations of electrical signal much like a tiny tornado, in areas of the right atrium with highest expression of adenosine receptors and its downstream potassium channels called GIRKs.
Fedorov’s team applied high-resolution optical and immunoblot mapping of the atria from 37 explanted failing and non-failing human hearts, which were donated for research by Lifeline of Ohio and the Division of Cardiac Surgery at Ohio State Wexner Medical Center. Unique mapping techniques recently developed at Ohio State captured panoramic images from both inside and outside the atrial walls.
“We indeed found reentrant drivers that were maintaining AF localized in the areas of the right atrium with the highest adenosine receptor and GIRK4 expression. Now that we know this, physicians may be able to inject adenosine to unmask the exact location of AF drivers to assist in targeted ablation treatment,” Fedorov said. “It may also be possible, in the future, to avoid invasive surgical ablation treatment altogether by treating this type of AF pharmaceutically with a selective GIRK channel blocker.”
The team evaluated tertiapin, an amino acid peptide derived from honey bee venom, as a treatment for adenosine-induced AF. Fedorov reported that tertiapin is a selective GIRK channel blocker and that it successfully stopped or prevented AF in the study.
“It is very encouraging that we’re able to see this type of human AF is driven by localized reentrant sources and help physicians better understand how and where the disease is occurring directly so they can better target their treatment,” Fedorov said.
This research was supported by grants from the National Institutes of Health. Fedorov also received funding support from the Ohio State University Heart and Vascular Center TriFit Challenge Discovery Fund, the CR Webb Fund in Cardiovascular Research and the American Heart Association.
Media Contact: Marti Leitch
Wexner Medical Center Media Relations