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ABSTRACT. The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p < 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vituo, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage. increased dead space and gas trapping (3-6). These findings underscore the need for determining the functional characteristics of immature airways. Numerous investigators have characterized the elastic and viscoelastic properties of the airways by using a variety of experimental techniques, in a number of species, and at different stages of development (5-13). To date, only one study, using in vitro rabbit tracheae, has examined airway mechanical properties throughout a range of early development according to a consistent protocol and experimental technique (5). Although this study has provided valuable information concerning age-related differences in airway mechanics, it is difficult to extrapolate these data to the fully innervated and perfused in vivo trachea. Furthermore, the in vitro preparation cannot address the influence of neuralhumoral and supporting structures on the in situ trachea, which may also be age-related.The in vivo study of airway physiology in the premature animal has been limited by the inability to maintain physiologic gas exchange and acid-base status that potentially could influence airway properties (14). Recent advances in liquid ventilation techniques have enabled us to establish a stable and viable preterm animal preparation to study physiologic development beginning at the early stages of gestation (15). Using this technology, we evaluated airway compliance and the relaxation time constant of in vivo tracheal seg...

In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment.

SummaryCardiopulmonary function was evaluated in very preterm lambs (106 + 0.7 S.E. days gestation, 1.66 -+ 0.12 S.E. kg birth weight) during fluorocarbon ventilation. Lambs were delivered by cesarean section after epidural anesthesia. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Lambs were then mechanically ventilated with oxygenated fluorocarbon for approximately 2 h. During this period it was possible to maintain adequate gas exchange and stable cardiac function. Transpulmonary pressure, liquid flow, and tidal volume tracings enabled determination of lung compliance, CL = 0.58 + 0.12 S.E. ml*cmHzO-' kg-', inspiratory resistance, RI = 3600 + 604 S.E. ~mHZO*liter-~*sec-', and expiratory resistance, RE = 4034 + 2183 S.E. cmH20/liter/sec. Lung compliance of the 106-day-old fluorocarbon-filled lung is similar to the more mature 138-143-day-old air-filled lung in preterm lambs. Based on the data presented herein we have extended the viability of the preterm lamb to the limit of pulmonary capillary development rather than that of the pulmonary surfactant system. AbbreviationsA-a DO2, alveolar-arterial oxygen gradient CL, lung compliance FRC, functional residual capacity RE, expiratory resistance RI, inspiratory resistance VT, tidal volumeThe lamb has been employed extensively for studying cardiopulmonary development in the perinatal period (1,2,3,12,18,21). But there are few data in very preterm .animals because cardiopulmonary stability and viability are highly correlated with maturity. The majority of studies are those in lamb fetuses at various stages of development (14), exteriorized lambs when the ewe was anesthetized (l,5), or in older lambs delivered by cesarean section after 125 days of gestation (12,18,19,21). Although adequate oxygen transport has been demonstrated by 110 days of gestation in exteriorized preterm fetal lambs, viability of these animals is much later (approximately 140 days, term 145-147 days).Recent studies have revealed the feasibility of ventilation with fluorocarbon liquid in preterm lambs delivered by cesarean section between 135-138 days gestation (17). In contrast to the respiratory problems that occur during mechanical gas ventilation (18, 19, 2 l), lambs ventilated with fluorocarbon liquid exhibited good gas exchange and stable blood gas tensions. It has been suggested that the elimination of high surface forces in the liquid-filled lung could account for improved gas exchange and respiratory stability. The first objective of this study was to quantitate baseline cardiovascular, gas exchange, acid-base balance, and lung mechanics data in very immature lambs using liquid ventilation techniques. There are also apparent differences in lung mechanics between the gas and liquid-filled lungs. With this in mind, we sought to correlate these changes with the differences in physical properties of the respiratory medium. MATERIALS AND METHODS Animalpreparation.Five preterm lambs of 106 -t 0.7 S.E. days gestation (70% of term gestation) and a mean b...

The relationship between pulmonary function and the migration of meconium to distal airways was determined in 10 rabbits (mean weight 2.6 kg) after insufflation of a meconium-saline mixture (1--2 ml/kg). Animals were anesthetized, cannulated, intubated, and mechanically ventilated with 100% oxygen. Lung mechanical dysfunction was most severe during the early phase of meconium migration, 15 min postinsufflation. Substantial increases in inspiratory lung resistance (RI) and expiratory lung resistance (RE) suggest that the site of obstruction at 15 min was the large airways. A decrease in dynamic lung compliance with unchanged static compliance characterizes the obstruction as partial. At 15 min and throughout the migration process, RE was greater than RI, demonstrating a check-valve effect. This phenomenon was substantiated by an increased functional residual capacity (FRC) in all rabbits, presumably due to gas trapping. Secondary to these changes, marked hypoxemia, hypercapnea, and acidosis developed in spite of assisted ventilation with 100% oxygen. At 60 and 120 min postinsufflation, both RI and RE decreased as compared to 15 min. This suggests that the predominant site of obstruction shifted to medium and small airways concomitant with the migration of meconium. Widespread and uneven distribution of meconium still produced significant frequency dependence of lung compliance. Static compliance remained unchanged, indicating that meconium does not affect surface-active or tissue properties of the lung within 120 min postinsufflation. These data suggest that effective respiratory management after meconium aspiration is dependent on the degree of meconium migration, as reflected by pulmonary mechanics.