To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108-116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the influence of body position on chest wall and pulmonary function, we studied the ventilatory, pulmonary mechanics, and thoracoabdominal motion profiles in 20 preterm infants recovering from respiratory disease who were positioned in both the supine and prone position. Thoracoabdominal motion was assessed from measurements of relative rib cage and abdominal movement and the calculated phase angle (an index of thoracoabdominal synchrony) of the rib and abdomen Lissajous figures. The ventilatory and pulmonary function profiles were assessed from simultaneous measurements of transpulmonary pressure, airflow, and tidal volume. The infants were studied in quiet sleep, and the order of positioning was randomized across patients. The results demonstrated no significant difference in ventilatory and pulmonary function measurements as a function of position. In contrast, there was a significant reduction (-49%) in the phase angle of the Lissajous figures and an increase (+66%) in rib cage motion in prone compared with the supine position. In addition, the degree of improvement in phase angle in the prone position was correlated to the severity of asynchrony in the supine position. We speculate that the improvement in thoracoabdominal synchrony in the prone position is related to alterations of chest wall mechanics and respiratory muscle tone mediated by a posturally related shift in the area of apposition of the diaphragm to the anterior inner rib cage wall and increase in passive tension of the muscles of the rib cage. This study suggests that the mechanical advantage associated with prone positioning may confer a useful alternative breathing pattern to the preterm infant in whom elevated respiratory work loads and respiratory musculoskeletal immaturity may predispose to respiratory failure.

Pulmonary vascular resistance was investigated in the fluorocarbon-filled lung in an in situ isolated lung preparation. Lungs were perfused at constant flow (100 ml X min-1 X kg-1) with whole blood from a donor cat. left atrial pressure was held constant at zero pressure. Measurements of pulmonary arterial pressure enabled calculation of pulmonary vascular resistance. Regional changes in pulmonary blood flow were determined by the microsphere technique. During quasi-static deflation over a range of 0-30 mmHg, dependent alveolar pressure was consistently greater for a volume of fluorocarbon than for gas, with each pressure-volume curve for the fluorocarbon-filled lung shifted to the right of the curve for the gas-filled lung. In turn, pulmonary vascular resistance was found to increase linearly as a function of increasing alveolar pressure, independent of the medium in the lung. Thus, for a given volume, pulmonary vascular resistance was consistently greater in the fluorocarbon-filled lung compared with the gas-filled lung. This increase in pulmonary vascular resistance was accompanied by a redistribution of pulmonary blood flow in which blood flow to the dependent region was decreased in the fluorocarbon-filled lung compared with the gas-filled lung. Conversely, the less-dependent regions of the lung received a relatively greater percentage of blood flow when filled with fluorocarbon compared with gas. These findings suggest that pulmonary vascular resistance is increased during liquid ventilation, largely as the result of mechanical interaction at the alveolar-vascular interface.

Extractnot only difficult to ventilate, but also hard to k e e~ alive. TheNine distressed premature lambs were studied before, during, and after ventilation with fluorocarbon liquid . It was found that premature lambs, delivered by cesarean section, could be adequately ventilated with oxygenated liquid for periods up to 3 hr. Using fluarocarbon liquid in conjunction with the described liquid breathing system, it was possible to maintain remarkably good pulmonary gas exchange and acid-base balance during normothermic conditions. In addition. ~e a k intratracheal Dressures measured during recovery from li&id ventilation wer; significantly reduced ( P < 0.001) as compared with preliquid ventilation values.This improvement in lung function is in direct contrast to the deterioration in that of the adult animal following liquid ventilation as reported previously. SpeculationAlthough an enormous amount of studies remain to be performed, at this time it is appealing to speculate about the possibilities of this therapeutic modality in the preterm human neonate with respiratory distress. We cannot help but think that this method of therapy serves a twofold purpose: ( 1 ) maintenance of infants with lungs too stiff to ventilate with gas, and (2) a treatment for reducing surface-active forces in infants with marginal lung stability.Liquid ventilation in mammalian species has been studied by various intestigators since 1958 (12). More recently, fluorocarbon liquids capable of dissolving larger volumes of respiratory gases at atmospheric pressure (3,10,14,17,22,24) were recognized as useful media for conducting oxygen-carbon dioxide transport studies. In particular, one of these liquids, FX-80, has been successfully emplqyed to ventilate the lungs of various adult species for periods of up to 8 hr (14). The effect of fluorocarbon liquid ventilation on pulmonary gas exchange (10, 17), surfaceactive properties (15), function (10,21,24,27), and structure (19) has been studied previously. In addition, in order to pave the way for clinical applications, long term experiments have been conducted looking for residual fluorocarbon as well as morphologic, biochemical, and/or histologic evidence of toxicity after ventilation with fluorocarbon liquid (I I, 16).The premature lamb has been employed by,various investigators as a model for studying many physiologic functions related to the human newborn (4,5,18,28). Measurements of pulmonary mechanics and acid-base balance in this animal (26) during the first few hours of life indicate decreased lung compliance, increased respiratory rate, vascular shunting, and increased work of breathing similar to the preterm human neonate with respiratory distress (I). Because of pulmonary immaturity, these animals were purposi of the present study was to evaluate the feasibility and efficacy of liquid ventilation as a therapeutic method In this animal model. Pulmonary gas exchange, acid-base balance, and inflation pressures were measured in these animals during the first few hours of life (a critical t...

Perfluorochemical (PFC) liquids are biologically inert and nonbiotransformable substances that, when used as breathing medium, may be transported across the lung epithelium in small quantities, distributed throughout the body, and ultimately vapourized through the lungs and transpired through the skin. To further evaluate the uptake, biodistribution and elimination of a PFC liquid (perfluorodecalin) in the neonatal population, arterial blood, tissue and expired gas samples were obtained from preterm lambs (105-114 days gestation). Two groups of premature lambs were studied: Group I (n = 4) lambs were liquid ventilated from birth for 1 h and killed without exposure to gas ventilation (GV) and Group II (n = 5) lambs were liquid ventilated for 1 h followed by up to 2 h of GV. Samples were analysed by electron-capture gas chromatography and data were expressed in nl of PFC/ml of blood or gas and nl of PFC/gm tissue. During liquid ventilation and subsequent GV, PFC blood levels significantly increased (P < 0.001) from baseline control levels (0.007 +/- 0.001 SE nl PFC/ml blood) to a high of 2.95 +/- 1.03 SE nl PFC/ml blood. Perfluorochemical levels measured in expired gas (Group II) demonstrated a rapid decrease as a function of time of GV. Tissue levels of PFC indicated that uptake of PFC in Group I was significantly different (P < 0.001) than baseline levels and organ dependent; the highest levels were in the lungs (221 +/- 26.2 SE nl PFC/g tissue) and the lowest in the liver (2.24 +/- 1.6 SE nl PFC/g tissue). Comparison of tissue levels of PFC between groups indicated a 34.8% mean decrease across organs in Group II compared with Group I. These data indicate that PFC uptake and elimination is organ dependent and that PFC liquids can be eliminated through the lungs upon return to GV. Sustained PFC blood levels may be related to residual PFC in the organs and lung as well as regional variation in ventilation-perfusion matching upon return to GV.