Am. J. Respir. Crit. Care Med., Vol 157, No. 1, 01 1998, 31-34.
Alveolar vascularization of the lung in a lamb model of congenital diaphragmatic hernia [In Process Citation]
A Ting, PL Glick, DT Wilcox, BA Holm, J Gil and M DiMaio
Department of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA.
Pulmonary hypoplasia and pulmonary hypertension are factors limiting the
survival of infants with congenital diaphragmatic hernia (CDH). A reduction
in the number of pre-acinar pulmonary vessels and increased muscularization
are the structural lesions implicated as causes of irreversible hypoxemia.
Whether there is a reduction in the number of air-blood barriers, which
represent the capillary surface area of the lung involved in gas exchange,
is unknown. We sought to determine if the lungs of CDH lambs have: (1) a
reduction in total capillary surface area proportionate to the reduction in
the total alveolar surface area of the lung; and/or (2) a disproportionate
reduction in the number of capillaries (air blood barriers) within each
acinus. The latter measurement was determined by calculating the capillary
load which we defined as the number of air blood barriers/unit of surface
density. At 80 d gestation (pseudoglandular period), a diaphragmatic hernia
was created surgically in one lamb fetus of a twin gestation. At term, the
fetuses were removed, the chests opened and the lungs fixed by a tracheal
infusion of 1.5% glutaraldehyde at 25 cm of water pressure. Tissues from
the lower lobes were examined by light and electron microscopy. Using
computerized interactive morphometry, alveolar and capillary surface area,
and capillary load were determined by intersection and point counting for
the right and left lungs. The data show that the total alveolar surface
area of the left CDH and control lungs were 1.8 +/- 0.8 m2 and 6.1 +/- 1.1
m2 (p < 0.01), respectively, and for the right CDH and control lungs 2.5
m2 +/- 0.1 and 11.2 +/- 1.9 m2 (p < 0.01), respectively. The total
capillary surface area for the left CDH and control lungs were 0.7 +/- 0.3
m2 and 2.8 +/- 1.2 m2 (p < 0.05), respectively, and for the right CDH
and control lungs 0.9 +/- 0.3 m2 and 3.8 +/- 1.5 m2 (p < 0.05),
respectively. The capillary load was not statistically different. These
findings demonstrate that the lungs in CDH are deficiently vascularized at
the alveolar surface due to a reduction in the total alveolar surface area.
Each acinus contains the same number of air blood barriers per unit of
alveolar surface area indicating a normal acinar composition.