Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Therapeutic role found for carbon monoxide

20.09.2006
Gas is shown to reverse symptoms of pulmonary hypertension

In a medical case of Jekyll and Hyde, carbon monoxide – the highly toxic gas emitted from auto exhausts and faulty heating systems – has proven effective in treating the symptoms of pulmonary arterial hypertension (PAH), an extremely debilitating condition that typically leads to right heart failure and eventual death.

The new findings, made in an animal study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and the University of Pittsburgh, are described in the September 2006 issue of The Journal of Experimental Medicine (JEM).

The paradoxical theory that carbon monoxide (CO), the colorless, odorless gas often dubbed "the silent killer," could be used to prevent the onset of certain inflammatory conditions was first proposed in 1998. Since then, numerous studies have shown that when administered at low, non-toxic concentrations prior to such procedures as organ transplant surgery or balloon angioplasty, CO provides potent protective effects against organ rejection or blockage of the carotid arteries.

But, with these latest findings, explains senior author Leo Otterbein, PhD, it now appears that carbon monoxide can also be used to treat and reverse existing disease.

"Our results offer the exciting possibility that in extremely low concentrations and for brief intermittent exposures of one hour per day, CO gas might be effectively used as a therapy to treat PAH in a clinical setting," says Otterbein, an investigator in the Transplantation Center at BIDMC and Associate Professor of Surgery at Harvard Medical School.

Pulmonary arteries – the blood vessels that carry blood from the heart's right ventricle to the small arteries in the lungs -- are made up primarily of endothelial cells and smooth muscle cells. PAH develops when, for unknown reasons, the smooth muscle cells rapidly and uncontrollably proliferate, leading to "remodeling," in which blood vessel walls thicken and gradual stenosis of the arteries occurs. Ultimately, the vessels thicken to the point that blood can no longer be effectively pumped through them, resulting in serious cardiopulmonary complications and in many cases, heart attack. There is no cure for the disease.

Based on CO's successful track record in helping to prevent vascular disease, Otterbein and first author Brian Zuckerbraun, MD, of the University of Pittsburgh, hypothesized that the gas might prove beneficial in treating pulmonary arterial hypertension.

To test this hypothesis, the scientists first exposed a PAH mouse model to a short, daily regimen of CO (in a modest concentration, equivalent to what a cigarette smoker might inhale) of one hour per day. As predicted, their results showed that the gas did indeed reverse PAH in the animals, resulting in the restoration of both normal pressures and heart weights (indicative of reversal of imminent heart failure).

The scientists next identified how this was happening.

"We determined that CO was exerting these effects by both arresting growth of the vessels' smooth muscle cells and inducing apoptosis, or cell death," he adds. Consequently, as the smooth muscle cells died, both the pulmonary blood vessels and right heart were restored to their normal size, what Otterbein describes as a case of "retro-remodeling."

"However, what we found most intriguing was that CO did not induce the death of all of the smooth muscle cells in the blood vessels, but rather selected out for destruction only the population that was problematic," he adds.

It was in the final arm of their study that the authors discovered how CO was able to selectively target the troublesome smooth muscle cells: It was relying on a second gas, nitric oxide (NO), for assistance.

"When we first started these experiments, we had the cells separated into two separate culture dishes – endothelial cells in one, smooth muscle cells in the other," explains Otterbein. But, he adds, when they exposed these cultures to carbon monoxide, nothing happened. The cells behaved normally.

"We eventually asked ourselves, 'What if we're not seeing results in these two separate dishes because in the body, the two aren't separated. What if these two cell types somehow act in concert and need to communicate with one another as they otherwise would in vivo in order for CO to exert its beneficial effects?'"

To address this question, coauthor Beek Yoke Chin, PhD, developed a simulated blood vessel by growing the cells on a semi-permeable membrane, which enabled the two cell types to "communicate" with one another through pores. And that, says Otterbein, was when the scientists observed that in this "co-culture" setting, CO was able to induce death of the smooth muscle cells without adversely affecting the viability of the endothelial cells.

"We discovered that endothelial cells must be present – and be able to generate NO via nitric oxide synthase [NOS3] -- in order for CO to induce the death of the smooth muscle cells and reverse the symptoms of PAH," explains Otterbein. To further test the role of the nitric oxide, the co-culture was treated with a select inhibitor of NOS3. Under these conditions, he adds, CO was unable to induce death to the same degree as in control-treated co-cultures.

"We concluded that the physical interaction between the two cell types plus the ability to generate NO was crucial for the positive CO effects," he says, adding that studies are now underway to determine the mechanism by which CO exposure leads to the increase in NO generation.

"Our hope is that CO will find a place in the clinic as a therapeutic option for the treatment of disease," concludes Otterbein. "CO has been around since before life began on earth and, in fact, it is thought to have contributed to the origin of life. Perhaps this was a sign of its necessary role in biology."

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>