4d-4 pulmonary airways in adult sheep following intrauterine growth restriction
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S68 Oral Submitted Presentations
features akin to adult metabolic syndrome. One way ANOVA defined
differences in hsCRP, uric acid, ALT and GGT in the cluster groups.
Results: The high risk group had higher BMI (x = 27.9, SD = 5.1 vs
x = 20.2, SD = 2.6, p < 0.001), SBP (x = 120.1, SD = 12.0 vs x = 112.1,
SD = 10.4, p < 0.001), insulin (x = 24.6, SD = 15.7 vs x = 10.2, SD = 4.6,
p < 0.001), triglycerides (x = 1.5, SD = 1.0 vs x = 0.9, SD = 0.3,
p < 0.001) and lower HDL (x = 1.2, SD = 0.3 vs x = 1.4, SD = 0.3,
p < 0.001). Markers of inflammation and liver function were higher
in the at risk group; hsCRP (x = 2.15, SD = 4.7 vs x = 0.7, SD = 2.7,
p < 0.001), uric acid (x = 0.34, SD = 0.08 vs x = 0.29, SD = 0.06,
p < 0.001), ALT (x = 21.23, SD = 9.7 vs x16.21, SD = 7.23, p < 0.001)
and GGT (x14.6, SD = 5.9 vs x11.0, SD = 4.0, p < 0.001). The highest
hsCRP levels were only present in children within the cluster who
were also overweight.
Conclusions: This suggests that inflammation exists in at risk
children as early as 13 years, preceding overt atherosclerosis.
It provides clues to the pathogenesis of inflammation in
cardiovascular disease by showing that neither being overweight
or within the metabolic syndrome cluster alone is associated with
raised CRP, but requires the combination of both. It supports
early intervention for preventing childhood obesity and subsequent
cardiovascular disease.
4C-7 Maternal flu infection during pregnancy impacts brain
and behavioral development in the infant monkey
S.J. Short1 *, C.L. Coe1, G. Lubach1, M. Styner2,3, J.H. Glimore.1Department of Psychology, University of Wisconsin, Madison, WI;2Department of Computer Sciences, University of North Carolina,
Chapel Hill, NC; 3Department of Psychiatry, University of North
Carolina, Chapel Hill, NC, USA
E-mail: [email protected]
Aims: Experimental research in rodents and retrospective studies
of children indicate an increased risk for developmental disabilities
and psychopathology following particular viral infections during
pregnancy. Development of a nonhuman primate model that utilizes
a human derived strain of flu is necessary for understanding the
mediating mechanisms and neural impact on the offspring.
Study design: Pregnant rhesus monkeys were infected with the
flu (H3N2 A/Sydney/5/97) 1 month before term. Viral shedding
and generation of flu-specific antibody confirmed the infection.
Offspring are then evaluated: (1) neurobehavior, (2) mother infant
interactions, and (3) brain development.
Subjects: Preliminary assessments of 19 monkeys from control
(n = 7) and virally infected (n = 12) pregnancies.
Outcome Measures: A standardized test battery is used after birth
to assess neonates levels of arousal, motor development, and
attention. Weekly observations of mother and infant interactions
are recorded until 3 months of age. High resolution neuro imaging is
performed at 1 year of age for determining overall gray and white
matter and comparing regions of interest.
Results: Flu infants scored higher on measures of distress and lower
on measures of motor development (p < 0.05) at 2 weeks of age. Flu-
exposed infants initiated autonomy earlier (p < 0.05) despite signs
of distress. MRI analyses revealed significant reductions in total
brain volume and overall hemispheric gray matter (p < 0.05) in flu
animals.
Conclusions: These findings demonstrate that a moderate viral
infection during pregnancy can adversely affect behavioral and
neural development. Reductions in gray matter will be reassessed
after puberty to further examine neurodevelopmental changes in
brain structure and volume.
4D-4 Pulmonary airways in adult sheep following intrauterine
growth restriction
R. Harding1 *, M. O’Reilly1, N. Brew1, K. Snibson2. 1Department of
Anatomy and Cell Biology, Monash University, VIC 3800, Australia,2School of Veterinary Medicine, University of Melbourne, VIC
3010, Australia
E-mail: [email protected]
Aim: Low birthweight is associated with reduced lung function in
adults but the structural basis is largely unknown. We recently
showed that IUGR leads to fewer, larger alveoli in adult sheep
(Maritz et al., Pediatr Res 2004) but effects on pulmonary airways
have not been examined. Our aim was to determine the effects of
IUGR on airway structure at adulthood.
Methods: Pregnant ewes underwent aseptic surgery for implanta-
tion of fetal aortic and femoral vein catheters. Using microspheres,
umbilical-placental embolization (UPE) was performed daily from
120 days’ gestation until labour onset at term (~147 days). UPE
lowered fetal SaO2 by ~50% and birthweight by 41%. At ~2.2 yrs of
age, offspring were euthanized and organs collected; the right lung
was perfusion fixed via the airway at 20 cmH2O and prepared for
histological examination. Sections (5m) were stained with Masson’s
trichrome and bronchiolar walls analysed morphometrically on
coded slides.
Results: Bronchiolar lumen area, basement membrane perimeter,
total wall thickness, smooth muscle area and collagen area were
not different between IUGR and control sheep. The number of
alveolar attachments, in relation to airway perimeter, was 8% less
in IUGR sheep than in controls (p < 0.05).
Conclusions: Adult sheep that were subjected to IUGR have normal
bronchiolar walls but reduced numbers of alveolar attachments.
Reduced alveolar tethering of small airways, as seen in smokers and
COPD, could contribute to a faster decline in lung function with
age. This could contribute to the association observed in human
populations between low birthweight and reduced lung function.
4D-5 Intrauterine growth restriction alters fetal
lung programming by affecting essential
epithelial-mesenchymal signaling pathways
A. Karadag1 *, R. Sakurai1, J. Belperio3, H. Guang2, M. Desai2,
M.G. Ross2, J.S. Torday1,2, V.K. Rehan1. Departments of 1Pediatrics
and 2Obstetrics and Gynecology, Los Angeles Biomedical Research
Institute at Harbor UCLA, Torrance, California, USA, 2Department
of Pulmonary and Critical Care Medicine, David Geffen School of
Medicine at UCLA, Los Angeles, California, USA
Aims: Intrauterine growth restriction (IUGR) increases the risk of
respiratory compromise throughout postnatal life. However, the
molecular mechanism(s) underlying the respiratory compromise
following IUGR is not known. Since lung development is determined
by spatio-temporally specific alveolar epithelial-mesenchymal
interactions, we hypothesized that IUGR would affect the key
alveolar epithelial-mesenchymal signaling pathways that are
essential for normal lung development.
Study design and Subjects: We utilized a rodent model of 50%
maternal food restriction (MFR) from day 10 of gestation to term
and studied the offspring at postnatal day (PND) 1, 3 weeks, and
9 months.
Outcome measures: Lung morphometry, pulmonary function tests
(PFTs), and Western blotting for the molecular markers of
the key alveolar epithelial-mesenchymal signaling pathways that
determine alveolar structure and function. The specific markers
examined included peroxisome proliferator-activated receptor
gamma (PPARg), vascular endothelial growth factor (VEGF) and
VEGF receptor2 (FLK-1), a-Smooth Muscle Actin (SMA), calponin,
elastin, and glucocorticoid receptor (GCR).
Results: In general, MFR increased the expression of extracellular
matrix proteins aSMA, and calponin, but decreased the expression
of elastin at all time points examined. The expression of VEGF
and its receptor FLK-1, PPARg, and GCR was decreased at 3 wks
and 9 months. Further, in contrast to significant changes in lung