Lung Water and Proton Magnetic Resonance Relaxation in Preterm and Term Rabbit Pups: Their Relation to Tissue Hyaluronan

Abstract

The present study was performed to investigate simultaneously total lung water, T 1 and T 2 relaxation times, and hyaluronan (HA) in preterm and term rabbits. Attempts were also made to establish the relationship of HA to total lung water and to T 2 -derived motionally distinct water fractions. Experiments were performed in fetal Pannon white rabbit pups at gestational ages of 25, 27, 29, and 31 d and at a postnatal age of 4 d. Lung tissue water content (desiccation method), T 1 and T 2 relaxation times (H 1 -NMR method), and HA concentration (radioassay) were measured, and free and bound water fractions were calculated by using multicomponent fits of the T 2 relaxation curves. Lung water content and T 1 and T 2 relaxation times were highest at a gestational age of 27 d and then declined steadily during the whole study period. Similar trends and time courses were seen for the fast and slow components of the T 2 relaxation curve. The T 2 -derived free water fraction remained unchanged at a gestational age of 25-29 d (ϳ67%), but increased progressively to a value of 78.5 Ϯ 7. During fetal life the potential air space of the lung is filled with fluid, which is generated by continuous epithelial secretion driven by active chloride transport. As parturition approaches, the lung fluid secretion decreases, and sodium transport-dependent reabsorption begins. This switch in transepithelial water movement culminates at birth and results in rapid clearance of lung fluid, which is critical for successful transition to air breathing (1-4).The osmotic water permeability of the alveolar epithelium is developmentally regulated by and related to the expression of water-transporting proteins, called AQPs. Three AQPs have been identified in the lung: AQP1 in the capillary endothelium, AQP4 in the basolateral membrane of the airway epithelium, and AQP5 in the apical membrane of alveolar epithelial type I cells (5-8).The specific localization of AQPs to endothelial and epithelial cells suggests water movement between the air space and the interstitial and capillary compartments. It takes place through individual water channels. The mRNA and protein expression of AQPs appears late in gestation, increases markedly at birth, and remains elevated during early postnatal life (9, 10). This developmental pattern of AQP expression parallels perinatal changes in the osmotic water permeability of the lung and the rate of lung water removal that occurs around birth (11).In addition to active ion transport-driven AQP-mediated water transport, the physical state of tissue water is also an important determinant of perinatal lung water clearance. Namely, a fraction of tissue water is motionally constrained, i.e. bound to macromolecules and thus made unavailable for immediate transport across alveolar, microvascular, and airway barriers (12).

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

“…Recently, Krause et al (10) reported EVLW values obtained by single thermodilution and by gravimetric assessment in 2-to 10-day-old piglets (weighing 2700 ± 700 g) after pulmonary edema induced by repeated airway lavages, although the basal EVLW values were not reported. Other species such as rabbits have higher mean EVLW values than piglets, with 4-day-old rabbits having 83% LW content compared to wet lung weight, higher than that observed in the present study (33). The increase in EVLW after meconium aspiration has been reported previously in pigs and human beings.…”

Hyaluronan in the Human Neonatal Lung: Association with Gestational Age and Other Perinatal Factors

“…This is compatible with the concept that immobilization of water is one of the major functions of tissue hyaluronan. However, in a study by Sedin et al [25] in preterm and term rabbit pups, the lung hyaluronan concentration correlated positively with the total lung water, but not with the bound water fraction, as determined by proton nuclear magnetic resonance. The lung water content and the lung hyaluronan concentration are known to covary in many inflammatory conditions [19], but in healthy experimental animals no significant association between these two variables has been found during the period around birth [3,4], i.e.…”

Prediction of postnatal outcomes in congenital diaphragmatic hernia using MRI signal intensity of the fetal lung

“…Secretion of lung fluid in future airspace results in an accumulation of free protons and the decrease of the water binding hyaluronic acid fraction, which could be responsible for the changing appearance on T2-weighted sequences. 11,20,21 Furthermore, the production of surfactant and surfactant proteins may have an impact on MR signal properties, especially after gestational week 30. 22,23 Although the pathogenesis of pulmonary hypoplasia in CDH remains poorly understood, the fetal lung fluid has a key role in normal lung development as is mentioned.…”