The investigators found that infants suffering from PPHN had lower levels of citrulline, arginine and nitric oxide metabolites compared to infants with respiratory distress who did not develop PPHN. Genetic variants of the CPSI enzyme differed in the entire group of infants, relative to the general population and specifically for patients who developed PPHN.
"The ability to generate nitric oxide seems to be dependent on what kind of capacity these infants have in their urea cycle, which in turn depends on a genetic change that affects the function of the cycle," Summar said. "It's a change that isn't going to cause a problem during everyday wear-and-tear. But under the severe stress conditions of the newborn period, these infants can't process enough material through the urea cycle, can't make as much nitric oxide as they need, and go on to develop pulmonary hypertension."
There is likely a threshold level of nitric oxide required to make the transition from fetal circulation to normal circulation, Summar said, and infants who develop PPHN don't make that threshold. "It's probably due to several factors, one of which is the urea cycle not working quite right."
In fact, he added, our data suggest that genetic variation that affects the urea cycle might predispose infants to respiratory distress in general. The investigators will broaden their study to include infants who have risk factors for respiratory distress-things like lack of oxygen during birth and inhalation of meconium waste-but do not develop any lung disease.
In a new set of studies, Summar and colleagues will supply urea cycle intermediates like citrulline and arginine to at-risk infants to "s
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Contact: John Howser
john.howser@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
13-Jun-2001