Research uncovers potential therapy to prevent arrhythmias, sudden cardiac death after heart attack

PORTLAND, Ore., Feb. 2, 2015 /PRNewswire/ -- A therapy currently under development for spinal cord injuries has been shown to stimulate nerve regeneration in the heart and provide resistance to arrhythmias following a heart attack, according to a new study published today in the journal Nature Communications.

Millions of people have heart attacks each year, and those who survive have an increased risk of arrhythmias and sudden cardiac death. Recent clinical trials in human subjects have shown that the severity of nerve degeneration in the heart caused by heart attack predicts increased arrhythmia susceptibility. Currently, surgical implantation of a defibrillator is one of the only therapies proven effective for the treatment of life-threatening arrhythmias following a heart attack.

"Our study initially sought a therapy that would stimulate nerve regeneration after a heart attack. It was a surprising and thrilling discovery that not only could this regeneration be achieved through both genetic and pharmaceutical approaches, but that it also decreases the heart's susceptibility to arrhythmias," said Beth Habecker, Ph.D., senior author and professor of physiology and pharmacology in the OHSU School of Medicine. "We are excited to use these findings to pursue the development of therapeutics for post-heart attack care."

Habecker led a team of researchers at Oregon Health & Science University in determining why nerves were excluded from the cardiac scar after a heart attack. Co-investigator Ryan Gardner, Ph.D., found that factors preventing nerve regrowth after a spinal cord injury were also present in the heart, and that by blocking their actions in mice via genetic knockout or pharmaceutical therapy, nerve regeneration occurred and arrhythmia susceptibility decreased. Gardner contributed to this study as part of his graduate work in neuroscience at OHSU. The therapy that proved successful was Intracellular Sigma Peptide, a nerve therapy for traumatic spinal cord injury developed by Jerry Silver, Ph.D. and colleagues at Case Western Reserve University. To better understand why nerve regeneration prevented arrhythmia, OHSU researchers worked with co-investigators at UC Davis to assess the effects of nerve regeneration on electrical activity, calcium handling and arrhythmia susceptibility in the heart.

"Arrhythmia is one of the most unpredictable and life-threatening outcomes of a heart attack," said Crystal Ripplinger, Ph.D., assistant professor of pharmacology at the UC Davis School of Medicine. "Until now, we had always assumed that arrhythmias were mainly due to damage and death of heart cells. Our study is the first to suggest that treatments targeting nerve regeneration can normalize electrical activity and prevent arrhythmias in heart attack survivors. This exciting finding opens the door to an entirely new avenue of anti-arrhythmic therapy."

The paper, "Targeting protein tyrosine phosphatase after myocardial infarction restores cardiac sympathetic innervation and prevents arrhythmias," has implications for patients who survive a heart attack, and remain at risk for severe cardiac arrhythmias and sudden cardiac death. Heart attack survivors often receive an implanted defibrillator, which can carry its own risk of infection or malfunction. This research highlights the link between nerve degeneration and arrhythmia susceptibility in a way that when applied to future study in humans can better predict those patients most likely to benefit from implantable cardioverter defibrillators (ICD), and may one day provide an alternative treatment to ICD therapy.

This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award numbers HL093056, HL068231 and HL111600; the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number NS25713; the American Heart Association under award number 12SDG9010015; and an Oregon Brain Institute Neurobiology of Disease Fellowship.

OHSU researchers who contributed to this research include: Habecker, Gardner, Cassandra Dunbar and Bill Woodward.

About OHSU

Oregon Health & Science University is a nationally prominent research university and Oregon's only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children's Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university's social mission. OHSU's Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer's disease and new treatments for Parkinson's disease, multiple sclerosis and stroke. OHSU's Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.

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SOURCE Oregon Health & Science University

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