Biomedical subjects

J W DiFiore

Publications and source records attributed to J W DiFiore.

4 recordsLinked to original sources

PubMed1995

Experimental fetal tracheal ligation and congenital diaphragmatic hernia: a pulmonary vascular morphometric analysis.

The authors have previously shown that fetal tracheal ligation (TL) reverses the pulmonary hypoplasia in experimental diaphragmatic hernia (DH) by accelerating fetal alveolar growth. The purpose of this study was to determine if growth of the accompanying macroscopic and microscopic pulmonary vasculature is also accelerated. Eighteen fetal lambs were divided into three experimental groups: diaphragmatic hernia (DH), DH and simultaneous tracheal ligation (DH/TL), and sham-operated controls (C). Animals were delivered near term, the lungs retrieved, and pulmonary capillary growth (5 to 50 microns in diameter) evaluated by standard morphometric techniques. Capillary ultrastructure was evaluated by electron microscopy. Nine additional fetal lambs of the same gestational age were equally divided into the same three groups and their lungs analyzed by pulmonary arteriography for evaluation of large vessel growth (< 100-microns diameter). Computer digital analysis of angiogram lung slices showed that the total area of large vessels was increased in DH/TL lungs when compared with DH lungs and decreased in DH lungs when compared with C lungs (P = .003); however, the ratio of large vessel area per unit of lung area was similar in all groups. Microscopic morphometry of the capillary bed showed that the total number of capillaries was increased in DH/TL lungs over both DH and C lungs (P = .0001); however, the number of capillaries per alveolus (cap/alv) was similar in all groups. In DH/TL lungs, electron microscopy showed normal capillary wall structure and normal thickness of the capillary-alveolar interface, whereas in DH lungs, capillary structure was abnormal and the capillary-alveolar interface was thickened.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed1994

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Lung development.

Human lung development is divided into five stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. The boundaries between these stages are not sharp; rather, overlap occurs between various gestational ages and individuals. The anatomic and morphological characteristics of each stage are described; general principles of lung development and cytodifferentiation of type I and type II pneumocytes are discussed. The complex phenomenon of lung development incorporates two processes--lung growth and lung maturation. Although these processes are developmentally related, they appear to be separately controlled. Lung growth seems to be influenced primarily by physical factors such as intrathoracic space, lung liquid volume and pressure, and amniotic fluid volume among others. Special attention is given to fetal lung liquid dynamics and the effects of its manipulation on lung growth, particularly by tracheal occlusion. Lung maturation has two components--structural and biochemical (ie, surfactant). Structural lung maturation appears to be regulated by physical factors. Physical factors that produce hypoplasia produce structurally immature lungs, whereas physical factors that produce hyperplasia produce structurally mature lungs. Biochemical maturation appears to be hormonally regulated by several endocrine organs (pituitary, adrenal, thyroid) and a host of endocrine factors including corticotropin, cortisol, thyroid hormones, and others.

Animals↗

PubMed1993

Experimental fetal tracheal ligation prevents the pulmonary hypoplasia associated with fetal nephrectomy: possible application for congenital diaphragmatic hernia.

Pulmonary hypoplasia has a definite clinical impact in a variety of congenital diseases such as renal dysplasia and congenital diaphragmatic hernia. These diseases have in common inadequate growth and development of fetal lungs. Previous reports have demonstrated increased lung growth with in utero tracheal ligation. The purpose of this study was to determine if lung growth can be accelerated in the setting of experimental pulmonary hypoplasia. Ninety-five-day gestation fetal sheep were divided into four experimental groups: nephrectomy, nephrectomy with tracheal ligation, tracheal ligation alone, and sham-operated control animals. Animals were delivered near term and their lungs inflation fixed at 25 cm H2O. Total alveolar number (Alv#), total alveolar surface area (AlvSA), and lung volume to body weight ratios (LV:BW) were determined for apical and basilar segments of each animal and then averaged. Total lung DNA and protein content were also analyzed. The nephrectomy group had smaller lungs than control animals with decreased Alv#, AlvSA, and LV:BW. In contrast, nephrectomy with tracheal ligation produced large lungs which had increased Alv#, AlvSA, and LV:BW when compared with both the nephrectomy and the control group (P < .01). Total lung DNA and protein concentrations were both markedly elevated in the tracheally obstructed groups. However, the DNA/protein ratios remained constant in all four groups, suggesting that lung growth had occurred through cell multiplication. Photomicrographs of the lung demonstrated a histologically immature appearance in the nephrectomy group and a histologically mature appearance in the tracheally obstructed groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗