The 5 million or so heart failure patients in this country traditionally have been treated with nitroglycerin or other drugs that release nitric oxide into the bloodstream. While these medicines increase the heart's ability to contract, they also blunt chemical signals allowing the heart to fully relax and pump most effectively.

Now, animal research directed by Johns Hopkins researchers suggests that a chemical relative of nitric oxide could better restore normal function to failing hearts.

Studying normal dogs and those with heart failure, researchers gave the animals an infusion of the compound Angelis' salt, which generates a form of nitric oxide called nitroxyl anion. Nitroxyl anion is closely related to nitric oxide, but with an extra electron, or negative charge. This small change doubled the hearts' ability to contract, enhanced their ability to relax and stimulated the release of calcitonin gene-related peptide (CGRP), a native protein that dilates blood vessels. A report on the work is published in the April 15 issue of the Proceedings of the National Academy of Sciences.

"This is a truly novel pathway for stabilizing a failing heart," says David A. Kass, M.D., senior author of the study and professor of medicine and biomedical engineering at Johns Hopkins. "In our study, a single infusion produced a substantial improvement in both the contraction and relaxation components of heart function and this was particularly notable in failing hearts. There did not appear to be any toxicity associated with these effects. This could prove to be a useful alternative to traditional nitric oxide treatments that only enhance part of the pumping cycle."

Heart failure, which prevents the heart from pumping enough blood to the body, strikes an estimated 550,000 Americans each year. Heart attack, high blood pressure and heart valve dise
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Contact: Karen Blum
kblum@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
14-Apr-2003