Persistant pulmonary hypertension research
Persistent pulmonary hypertension (PPHN) is a serious clinical problem that
occurs in some newborn infants when the blood vessels of the lung do not adjust
normally during the transition to breathing air at birth.
Although inhaled nitric oxide (NO), a new therapy approved by the FDA in
December 1999, helps many newborns with PPHN, a substantial number of infants do
not respond initially or do not sustain their positive response to the gas. In
addition, pulmonary hypertension may worsen considerably when NO is discontinued
after as little as 24 hours of inhalation.
Researchers are only beginning to understand how and why NO works. Known to
be a potent oxidant that can damage the lung, NO appears to work through
increasing concentrations of a messenger molecule called cyclic GMP in the
smooth muscle cell.
Scientists at Children's are examining whether the formation and breakdown of
this messenger molecule occurs normally in PPHN. They are also evaluating the
role of other oxidants in producing or aggravating PPHN and whether they
interact with NO.
The researchers' ultimate goal is to develop new therapies that safely work
with NO, thereby allowing the blood vessels of the lung to relax more normally.
Research faculty members
Stephen M. Black, PhD, received his PhD from the University of
Edinburgh, Scotland, in molecular pharmacology and completed postdoctoral
training at the University of Edinburgh and the University of California, San
Francisco. His research program is funded by the National Institutes of Health,
and his specific interests include regulation of nitric oxide synthase activity
in neuronal cells and pulmonary vasular endothelial cells.
Robert Dettman, PhD , received his PhD from Indiana University and
completed postdoctoral training at the University of California, San Francisco.
He is a recent recipient of the Richard D. Rowe research award from the Society
of Pediatric Research. His interests focus on determining vascular precursors in
the developing heart.