Therapeutic nitric oxide from air with an electric spark

Photo: Nitric oxide (NO) generator

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; © Brian Wilson, Massachusetts General Hospital

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.

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 Dollars – 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.; Source: Massachusetts General Hospital

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