Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New class of compounds promises to revive failing hearts


Nitroxyl-releasing drugs seem to strengthen cardiac contractions, relaxation in conscious dogs

Half a million Americans are diagnosed each year with heart failure, a progressively debilitating condition characterized by the heart’s declining ability to pump blood efficiently. The condition causes about 50,000 deaths annually and accounts for 1 million hospitalizations – more than for all forms of cancer combined.
Since the 1980s, nitroglycerin and other medications that release nitric oxide (NO) into the bloodstream have been the usual approach to treating this condition. Though these drugs benefit the ailing heart by improving its ability to relax, they also have a negative flipside: they leave the heart with a diminished capacity for pumping.

Hoping to improve on that formula, researchers at The Johns Hopkins University have developed a new class of NO-based compounds called nitroxyl (HNO) precursors that produce HNO. In early studies, these compounds seem to play a role in protecting the cardiovascular system from further damage during heart failure and in restoring function to organs affected by the debilitating condition. Scientists will announce their results in late August at the American Chemical Society’s annual summer meeting, held this year in Philadelphia.

"Our results are preliminary, but very promising," said John P. Toscano, professor in the Chemistry Department in the Krieger School of Arts and Sciences at Johns Hopkins. "Our goal is not only to develop new classes of nitroxyl precursors, but also to figure out the mechanisms by which they seem to affect heart function. This has the potential to lead to alternative treatments for cardiac failure in humans. But we are still in the very early testing stage."

Toscano’s research partner, Nazareno Paolocci, assistant professor in the Department of Cardiology at The Johns Hopkins School of Medicine, administered normal, conscious dogs and those with heart failure with a compound called Angeli’s salt, which generates HNO. It turned out that this treatment doubled the dogs’ hearts’ ability to pump and enhanced their ability to relax between contractions -- a promising development.

"Our previous work in collaboration with Dr. David A Kass (of Johns Hopkins) and Dr. David A Wink (of the National Cancer Institute) has shown that nitroxyl donors appear to be very good candidates to treat failing hearts that are characterized by pressure overload, poor contractile function and delayed relaxation. Moreover, these compounds can be successfully combined with other drugs used in heart failure patients, namely, beta-blockers," Paolocci said.

Essentially all physiological studies probing the effects of nitroxyl have used Angeli’s salt as a donor of that substance, prompting Toscano’s team to set to work to develop new sources. New nitroxyl donors not only would confirm that the physiological effects seen with Angeli’s salt are truly due to HNO, but they also would help researchers determine if the rate of HNO release had any effect on the resulting physiological response.

"One of the main reactions of nitroxyl is dimerization – that is, the reaction of one HNO molecule with another – which is dependent on the local concentration," Toscano said. "So, compounds that release HNO at faster rates generate higher initial concentrations of it and therefore may result in HNO being consumed by the dimerization reaction, rather than being available to elicit the desired physiologic response."

So far, Toscano’s team has cultivated one class of compounds based on the reaction of certain secondary amines with nitric oxide to form compounds called diazeniumdiolates, which traditionally are NO donors, but have been turned into HNO donors by Toscano’s team.

Paolocci and his team have tested two of these derivatives – one a pure HNO donor, which behaves similarly to Angeli’s salt and one a pure NO donor, which behaves analogously to standard NO donors – on dogs to assess their cardiovascular action.

"We’re very optimistic with what we have seen so far," Toscano said. "This looks promising. We know that NO is an important biological molecule, and we are just beginning to learn that HNO may, in potentially very different ways, be just as important."

Lisa DeNike | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>