Navigation Links
Researchers work to take the pressure off newborns' lungs

AUGUSTA, Ga. Children born with heart defects that pummel their lungs with up to three times the normal blood volume quickly find their lungs in jeopardy as well.

Georgia Health Sciences University researchers are working to take the pressure off by augmenting a natural recycling system that enables blood vessels to temporarily handle the extra workload until the heart problem is resolved.

They've found that system isn't getting enough energy to generate sufficient nitric oxide, the powerful blood vessel dilator. But drugs called PPAR agonists, already in use for adult lung injury and to lower blood glucose and lipids in diabetes, may provide the boost small, fragile blood vessels need.

"Our goal is to help protect the babies' lungs until their heart defect can be corrected," said Dr. Shruti Sharma, molecular biologist at GHSU's Vascular Biology Center. About 1 percent of newborns have a heart defect with half requiring surgery. Improved surgical and medical treatments have increased survival rates but the risk of related lung disease also can be deadly as the high blood flow turns flexible pulmonary blood vessels into narrow, rigid pipes. The result, pulmonary hypertension, also puts additional strain on the heart.

Sharma is principal investigator on a four-year American Heart Association grant to better define key steps of the recycling system and whether increasing PPAR signaling can help restore optimal functioning of the system when it's needed most.

It's known that the amino acid arginine interacts with nitric oxide synthase to form nitric oxide and while these babies have plenty of arginine, they can't access it. Studies at GHSU and elsewhere have shown that the arginine found in the endothelial cells which line blood vessels are most important for nitric oxide generation. That's where recycling comes in.

Under normal conditions, arginine helps nitric oxide synthase produce nitric oxide as well as the byproduct citrulline which interacts with two enzymes that convert it back to arginine, repeating the process anew. Sharma's early findings show that high pressures from the heart defect disrupts the cell's powerhouse, or mitochondria. That means insufficient amounts of the energy source ATP are produced, hindering the function of the molecular chaperone, HSP90, which helps the enzymes do their job.

"Upstream you can see one thing getting disrupted and downstream all the molecules it's regulating are affected," Sharma said.

That's where PPAR agonists come in. Dr. Stephen Black, a cell and molecular physiologist at the Vascular Biology Center who co-directs the Cardiovascular Discovery Institute, has shown that PPAR signaling falters in their animal model of pulmonary hypertension, impairing the cell powerhouse. In fact by blocking PPAR signaling, the researchers have produced the negative effects on the blood vessels without the heart defect.

"We hope that adding a PPAR agonist will improve mitochondrial activity and function and downstream help improve arginine recycling and nitric oxide production," Sharma said. She is retracing the recycling process to see how the agonist impacts each known step as well as the desired bottom line of improved nitric oxide production. "We're optimistic that we can get these two enzymes back to doing what they are supposed to."


Contact: Toni Baker
Georgia Health Sciences University

Related medicine news :

1. Researchers map all the fragile sites of the yeast Saccharomyces cerevisiaes genome
2. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
3. Researchers discover new way to kill pediatric brain tumors
4. Researchers Who Discovered First Genes for Stuttering will Present Findings to the National Stuttering Association
5. Researchers create drug to keep tumor growth switched off
6. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
7. GUMC researchers say flower power may reduce resistance to breast cancer drug tamoxifen
8. Clemson researchers develop hands-free texting application
9. Researchers find biomarkers in saliva for detection of early-stage pancreatic cancer
10. Researchers chart genomic map spanning over 2 dozen cancers
11. Researchers discover second protective role for tumor-suppressor
Post Your Comments:
Related Image:
Researchers work to take the pressure off newborns' lungs
(Date:11/25/2015)... ... November 25, 2015 , ... Since its ... comprehensive solutions involving adult stem cell therapies to patients with chronic degenerative medical ... name as a Registered Trademark (RTM). , Organizations are required to hold a ...
(Date:11/24/2015)... ... November 24, 2015 , ... Dr. Todd S. Afferica, a noted ... to many of his patients. Dr. Afferica now uses the BIOLASE WaterLase iPlus 2.0™ ... of time the doctor uses other traditional cutting tools, such as the scalpel and ...
(Date:11/24/2015)... ... , ... In an article published November 12th by Obesity News ... or are not eligible for bariatric surgery. The article explains that candidates for weight ... 100 pounds overweight, or have a BMI of 35 and over with at least ...
(Date:11/24/2015)... Salt Lake City, UT (PRWEB) , ... November 24, 2015 , ... ... according to Forbes Magazine. For a business, it is critical that the first impression ... of a business, they are not likely to buy anything or want to return. ...
(Date:11/24/2015)... ... 2015 , ... Cancer patients, survivors, caregivers, family members and ... taping of the next CURE Connections® video series on Saturday, Dec. ... at Georgetown University Hotel & Conference Center in Washington, D.C. , CURE Connections, ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... , November 24, 2015 ... --> adds Latest Guidebook for ... of 217 pages published in November 2015 to ... online business intelligence library at . ... of the fastest growing global economies with a ...
(Date:11/24/2015)... LONDON , November 24, 2015 ... platform for scientists - since it was launched just six ... collaboration, reference management and authoring platform for scientists - since ... One million references have been loaded on to F1000Workspace ... for scientists - since it was launched just six months ...
(Date:11/24/2015)... , November 24, 2015 st  Scientific ... North America (RSNA) taking place in Chicago ... Booth 1122, Hall A. --> st  Scientific Assembly and ... (RSNA) taking place in Chicago ... Hall A. --> Molecular Dynamics will present its revolutionary ...
Breaking Medicine Technology: