Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mass. General team generates therapeutic nitric oxide from air with an electric spark

07.07.2015

Lightweight, portable devices to deliver pulmonary-blood-vessel-relaxing gas will allow trials of other important uses

Treatment with inhaled nitric oxide (NO) has proven to be life saving in newborns, children and adults with several dangerous conditions, but the availability of the treatment has been limited by the size, weight and complexity of equipment needed to administer the gas and the therapy's high price.


In this nitric oxide (NO) generator, which can be incorporated into a mechanical ventilator or anesthesia machine, air is taken in through the inlet on the left and passes by the electrode at the top of the vertical segment, where a series of sparks generates NO gas. The cylindrical chamber contains calcium hydroxide and a filter to remove toxic byproducts before the NO-enriched air exits on the right to be inhaled by the patient.

Credit: Brian Wilson, Massachusetts General Hospital Photography Department

Now a research team led by the Massachusetts General Hospital (MGH) physician who pioneered the use of inhaled nitric oxide has developed a lightweight, portable system that produces NO from the air by means of an electrical spark. The investigators describe their invention in the July 1 issue of Science Translational Medicine.

"Nitric oxide is used to treat about 35,000 hospitalized U.S. patients each year - mostly adults with pulmonary hypertension and infants with a condition called persistent pulmonary hypertension of the newborn (PPHN)," says Warren M. Zapol, MD, director of the MGH Anesthesia Center for Critical Care Research and emeritus chief of Anesthesia and Critical Care at the hospital, senior author of the Science Translational Medicine report.

"But NO therapy is very expensive - here at MGH five days treatment of a newborn with PPHN costs around $14,000 - and current systems use gas delivered in heavy tanks, making ambulatory treatment impractical. Our new system can economically make NO from the nitrogen and oxygen in the air using only small amounts of electric power. This device could enable trials of NO to treat patients with chronic lung diseases and certain kinds of heart failure and would make NO therapy available in parts of the world that don't have the resources that are currently required."

Not to be confused with the anesthetic gas nitrous oxide, nitric oxide was long considered to be only a toxic pollutant gas. But in the mid-1980s, three U.S. investigators discovered that it is a signal-transmitting molecule naturally used by the pulmonary, cardiac and other systems, a discovery that received the 1998 Nobel Prize. Among its many function, NO relaxes muscles surrounding blood vessels, which reduces blood pressure - a property that led Zapol and his colleagues to investigate its use to treat hypertension in vessels supplying the lungs.

Their discovery that inhaled NO selectively relaxed pulmonary vessels without producing a systemic drop in blood pressure led to the therapy's FDA approval in 1999 for the treatment of PPHN and other lung diseases in newborns. In 2003 Zapol and his former research fellow Claes Frostell, MD, PhD, received the Inventor of the Year award from the Intellectual Property Owners Association for the development of a system to safely deliver inhaled NO.

Since its FDA approval NO has been supplied to hospitals in large tanks of compressed gas and administered through bulky and complex delivery devices by trained respiratory therapists. However, in 1992 Zapol and the MGH were issued a patent for a system his team had developed to produce NO - which can be naturally produced by lightning bolts - from air by means of an electrical spark.

Although the discovery was licensed by two medical and industrial gas companies, the technology was never developed, possibly because the medical use of inhaled NO was only beginning to be accepted. In addition, the system originally invented by the MGH team was still too large for use in outpatient settings. The growing therapeutic use of NO along with technological advances including the availability of miniaturized electronic circuitry allowed the MGH team to develop the system described in the current report.

The investigators designed and built two prototype systems: in one the NO generator is a separate "offline" system continually generating gas that is delivered into a ventilation system via tubing; the second "inline" system is incorporated into the ventilation system in a way that synchronizes the generation of NO during inhalation with the pulsed delivery of oxygen and other gases to be inhaled, reducing the NO that would be lost during exhalation. Since generation of NO by an electric spark can also produce the toxic gases nitrogen dioxide and ozone, along with metal fragments from the electrode, both systems use calcium hydroxide and air filters to absorb and remove those byproducts.

A series of experiments helped the team determine the best metal to use for the electrode, which was determined to be iridium, and the optimal timing and number of electric sparks. Testing in an animal model revealed that the electrically generated NO produced by both systems was as effective as tank-delivered gas in relieving pulmonary hypertension.

Although a gas mixture containing 50 percent oxygen produced the highest NO levels, the amount produced from ambient air was sufficient for therapeutic use. Both systems continued to deliver therapeutic levels of NO for up to 10 days, and subsequent experiments with the inline system not included in this paper have continued for up to 28 days. There's no reason to think the system could not stably produce NO for even longer periods of time, notes Zapol, the Reginald Jenney Professor of Anæsthesia at Harvard Medical School.

"It's amazing how long this system continues to make NO," he says. "Once we've shown that this can safely be used in human patients with pulmonary hypertension - and we've got a clinical trial in progress right now - we'll be able to conduct studies of inhaled NO delivered in ambulatory settings, including patients' homes, to treat chronic pulmonary hypertension, right-sided heart failure and chronic obstructive pulmonary disease."

Richard Channick, MD, director of the MGH Pulmonary Hypertension Program, says, "This advance has great potential for our patients. If proven safe and effective, electrically generated NO therapy will greatly enhance our ability to treat many forms of pulmonary hypertension." Marc Semigran, MD, medical director of the MGH Heart Failure and Cardiac Transplant Service adds, "The ability to safely administer inhaled NO chronically to heart failure patients could improve the lives of many of the millions of patients with secondary pulmonary hypertension." Both physicians are collaborators with Zapol's research team although they are not co-authors of the current study.

###

Binglan Yu, PhD, of the MGH Anesthesia Center for Critical Care Research is lead author of the Science Translational Medicine report; additional co-authors are Stefan Muenster, MD, Aron Blaesi, PhD, and Donald Bloch, MD, all of the Anesthesia Center for Critical Care Research. Several additional patent applications covering the new system have been filed, and an option to license those patents has been granted to the startup company Third Pole, Inc.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Terri Ogan | EurekAlert!

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: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Mutation that causes autism and intellectual disability makes brain less flexible

20.11.2018 | Life Sciences

The sweet side of reproductive biology

20.11.2018 | Life Sciences

Fading stripes in Southeast Asia: First insight into the ecology of an elusive and threatened rabbit

20.11.2018 | Ecology, The Environment and Conservation

VideoLinks
Science & Research
Overview of more VideoLinks >>>