| dc.description.abstract | The lungs of a marsupial, the quokka wallaby (Setonix brachyurus) were examined
morphologically and morphometric ally at diverse age points from 3 days post partum to
adulthood and the qualitative and quantitative changes during postnatal development
determined. The objective of this approach was to establish the developmental events
taking place at various stages of the postnatal lung development in the quokka and also
to study the lung morphology in the adult quokka. The four stages of postnatal lung
development in the quokka namely, the canalicular (0-4 days), the saccular (5-125
days), the alveolar (125-180 days) and the microvascular maturation (150-400 days)
were investigated. The ultimate goal was to establish a potential animal model that
would allow flexibility in drug testing in terms of the developmental stages available
postnatally and their respective timescales.
Macroscopically the lung had a single left lobe, a right lobe and an accessory lobe. A
variable number of fissures divided the lung lobes into pseudo-lobes and some
indentations were observable on the parietal edges of the lobes. Microscopically, the
primitive tubules of the canalicular stage were converted to large saccules by day 5 with
secondary septa arising by day 15. There was subsequent reduction of size of air spaces, which lasted through the saccular and alveolar stages. There was increase in air space size during the stage of microvascular maturation coupled with thinning of interalveolar septa and development of pores of Kohn.
Early in the canalicular stage, the.tubules were lined with a low cuboidal epithelium
interrupted by a few isolated areas of the first thin portions of gas exchange barrier. The
septal interstitium was predominantly mesenchymal with no definitively identifiable cell
morphophenotypes. Towards the onset of saccular stage of development, gas exchange
barriers increased in number and much of the cuboidal epithelium changed to the
squamous type.
Quantitative analysis at light microscopy involved coarse lung parameters, which
included the volumes of the parenchyma, septal tissue, the non-parenchyma, and the
components of the latter, which included blood vessels, airways and connective tissue.
Between mid-canalicular stage and the onset of saccular stage, the lung volume
increased two-fold when major components of both the parenchyma and nonparenchyma were laid down. The dramatic increase in volume was, however, mainly
due to air space expansion as tubules converted to saccules, coupled with septal tissue
thinning. Except for the vascular component of the non-parenchyma, rate of increase of
the other parameters progressed in a decreasing order, being highest in the canalicular
and saccular stages and lowest in the alveolar stage, increasing again in the
microvascular maturation stage. It would appear that during the alveolar stage, the main
events involved growth and remodelling of the alveolar septa with air space subdivision
but with no marked tissue proliferation or air space expansion. Air space expansion
followed in the later part of alveolar stage and in the microvascular maturation stage.
The final adult lung volume was achieved by the process of equilibrated growth.
At ultrastructural ~vel the parameters estimated included the volumes of septal tissue ".
cotnponents and those of the air ~p'aces together with their respective surface areas.
Further tissue barrier. thicknesses and their diffusion capacities were computed. Most
parameters quantified showed a positive correlation with body mass in all the
developmental stages, except the volume of type II pneumocytes during the alveolar
stage when no significant correlation was observed. The volumes of the interstitium and
type II cells increased early in the saccular stage, the rate declining later in the alveolar
stage. Conversely, the volume of type I pneumocytes increased markedly in both
saccular and alveolar stages. Both capillary and endothelial volumes showed highest
rates of increase during the alveolar stage, a fact reflected also in the increase in
capillary surface area. Increase in alveolar surface area reached a peak during the
alveolar stage. The pulmonary diffusion capacity increased gradually, the rate being
highest in the saccular stage and the adult values attained were comparable to those of
eutherians. Although the quokka wallaby is born with the lung at a stage earlier than
any other reported mammal, the subsequent developmental stages characteristic of all
mammals were meticulously recapitulated. From the current findings, the quokka is
potentially an excellent animal model for testing paediatric drugs aimed at management
of lung related diseases.
On an already well-studied animal model, the laboratory rat (Rattus norvergicus) high
doses of dexamethasone phosphate were administered in the first 4 days of life to test
the effects of this drug on the morpho functional characteristics of the lung in the
immediate and prolonged post treatment period. At the fourth postnatal day, the treated
animals had rather enlarged air spaces, the interalveolar septa were thinner and more
mature with a single capillary system and secondary septa were few compared to the
lungs of the control rats. By day 10 post partum, the situation in the dexamethasone
treated rats was reversed the septa in the lungs of the treated rats were much thicker and had acquired a double capillary system, showing a new potency for secondary septa formation. Secondary septa were obviously more numerous in the experimental animals and had fewer mature septa at postnatal day 10. The morphology of the lung
parenchyma at 21 days was not much different between the control and experimental
animals, save for the rugged appearance of the septa in the latter group.
Dexamethasone treatment did not appear to confer any morpho-functional advantages to the lung. Body weight-normalized lung volume was boosted by day 21 at which time
body weight was depressed. Despite an improvement in the parenchymal proportion and capillary surface area by day 4 post partum, there was no significant increase in the
pulmonary diffusing capacity in the experimental animals. At day 60 postpartum, there
were no observable qualitative or quantitative differences. From these findings, it is
clear that dexamethasone treatment in postnatal life leads to a precocious maturation of
the septa and probably to an improved surfactant production and hence its observed
positive aspects in improving breathing in premature neonates. The treatment regime of
high-dose, short-term administration adopted here appears ideal since all the
morphological alterations undergo a reparative process by 36 days post partum. This is
indeed the protocol used by ciin'icians and the current study puts to rest the fears that
there might be long-term deleterious pulmonary effects after early treatment with
glucocorticoids.
The effects of glucocorticoids prior to the saccular stage remain unclear but as seen in
the current study, .the quokka wallaby offers an opportune animal model to introduce
such drugs at the canalicular stage of development. | en |
