A B S T R A C T Turnover and clearance of lung surfactant phospholipids were studied with particular reference to myoinositol-induced perturbation in the acidic phospholipids. Administration of myoinositol decreased [3H]palmitate and [32P]phosphate incorporation into phosphatidylglycerol by 80-90% in whole lung, and by 94-99% in lamellar bodies and in alveolar lavage. The increased incorporation of radioactive isotopes into phosphatidylinositol following myoinositol, was inverse to the decrease in phosphatidylglycerol incorporation. Myoinositol treatment affected neither content nor labeling of phosphatidylcholine or disaturated phosphatidylcholine as studied within 50 h of administration. Phosphatidylglycerol was pulse labeled by intravenous [32P]phosphate and [3H]-palmitate, followed by myoinositol. The biological half-lives of phosphatidylglycerol in the microsomal fraction, lamellar bodies, and alveolar lavage were 1.6, 4.6, 5.4 h (with 3H), and 2.8, 6.5, 7.0 h (with 32P), respectively.32P-labeled lung surfactant tracer was applied to the airways in saline suspension and the clearance of phospholipid radioactivity was measured in alveolar lavage, alveolar macrophages, lamellar bodies and lung homogenates. The clearance rates of phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylinositol as studied in whole lung over 6 h were 3.4-5.8% h. Only a small amount of phospholipid radioactivity was recovered in the alveolar macrophage fraction (including bis-[monoacylglycerol]phosphate). Phospholipid radioactivity in alveolar lavage fell to 40-70% of the maximum during the 1st h, and to 5-18% over the next

No abstract

No abstract

No abstract

Summaryoxygen exposure with simultaneous intravenous hypoxanthine infusion. Lung injury was induced in young rats by a continuous infusion of hypoxanthine intravenously and breathing 100% oxygen for 48 h (group 1). Control animals were rats infused glucose and MATERIALS AND METHODSbreathing 100% oxygen (group 2), rats infused hypoxanthine in room air (group 3), and untreated rats (group 4). In group 1 rats interstitial and alveolar edema was found with a tendency toward marked margination of polymorphonuclear neutrophils in small vessels (P < 0.025 compared with group 2). The main elastase inhibitor alphal-antitrypsin (a-1-PI) was significantly elevated in group 1; 2-, 3-and 5-fold, respectively, when compared with groups 2, 3, and 4. The surfactant phopholipids from alveolar lavage were normal in all groups. The protein-rich fraction of the lavage fluid from group I rats inactivated, however, the surface properties of lung surfactant. Minimum surface tension in group 1 rats was 14.5 dyn/cm compared with 7.0 dyn/cm in group 2, 2.9 dyn/cm in group 3 and 3.5 dyn/cm in group 4 (P < 0.05, group 1 and 2 versus 4). We conclude that the combination of hypoxanthine and high levels of oxygen causes lung injury, possibly via free oxygen radicals. We discuss the possibility that these findings demonstrate a basic pathogenetic mechanism for the hypoxic-hyperoxic insult and can contribute to the understanding of pathogenesis of a variety of diseases both in pediatrics and adult medicine. AbbreviationFree oxygen radicals have been shown to destroy cell membranes by lipid peroxidation (3, 8, 1 1, 2 1). It has been suggested that such radicals play an important role in the pathogenesis of the acute and chronic lung damage among patients treated with oxygen. Many authors have, however, suggested that oxygen must be combined with other more or less unknown factors, before injury occurs ( 14,27).Recently, it has been shown that the hypoxanthine/xanthine oxidase system generates free radicals (7), and that this system potently induces inflammatory changes both in the hamster cheek pouch (22) and the rat lung (16). Further, it has, by now, been well established that hypoxanthine accumulates in tissues (33), plasma (30,32,34,35), and other body fluids (12,23,25) during hypoxia. When high concentrations of oxygen are administered to the hypoxic patient, large amounts of free radicals may be produced by the hypoxanthine/xanthine oxidase system. We, therefore, have raised the question whether the combination of hypoxanthine and oxygen is more damaging than high oxygen alone to the lung. In the present study we evaluated this by investigating experimentally the effect on the rat lung to 100% Young female rats of the Wistar strain, weighing 170-230 g, were used. Four groups were investigated. Group 1, rats infused continuously with 5 mM hypoxanthine dissolved in 5% glucose and exposed to 98-100% oxygen (n = 10). Group 2, rats infused continuously with 5% glucose and exposed to 98-100% oxygen (n = 9). Group 3, rats infused continuously wit...