Biology Reference
In-Depth Information
Fig. 2 Ventilation of healthy neonatal sheep with 100% O
2
induces PDE5 protein expression
and activity. Ovine lung parenchyma and resistance PAs from healthy lambs ventilated with 100%
O
2
were harvested after 24 h and compared with both fetal lambs (Fetus) and healthy 1-day
nonventilated lambs (1DNV). (a) PA PDE5 protein expression was analyzed via Western blot,
with
b
-actin normalization. Data are shown as mean
SEM.
*
P
<
0.05 vs. fetal lambs,
#
P
<
0.05
vs. 1-day nonventilated lambs. (b) Lung PDE5-specific activity was measured as the sildenafil-
inhibitable fraction of total cGMP hydrolysis, normalized for total milligrams of protein (200
m
M
cGMP substrate in assay; 100 nM sildenafil for inhibition). Data are shown as mean
SEM.
*
#
P
<
0.05 vs. 1-day nonventilated lambs. (c) PDE5 expression is
localized within the PA smooth muscle and nearby airways. The
left column
shows phase-contrast
images (
P
<
0.05 vs. fetal lambs,
10) of frozen lamb lung sections. The
right column
shows the corresponding sections
stained for PDE5, with immunofluorescence shown as
red
. Reproduced with permission from
Farrow et al. (
2008a
)
milrinone, represent novel and particularly attractive new therapies for these infants
(Fig.
3
) (Lakshminrusimha and Steinhorn
2009
).
1.2.3 Congenital Diaphragmatic Hernia
CDH is a serious birth defect that includes disordered development of the diaphragm
and a variable degree of pulmonary hypoplasia. It occurs in 1 of every 2,000-4,000
live births and accounts for 8% of all major congenital anomalies. Severe CDH
develops early in the course of lung development, and as a result airway divisions
and alveolarization may be significantly impaired. Because development of the
pulmonary arterial system parallels development of the bronchial tree, fewer arterial
