Duration and characteristics of treatment of premature lambs with natural surfactant.

Jobe, Alan H.; Ikegami, Machiko; Glatz, Theodore H.; Yoshida, Yoshiro; Diakomanolis, Emmanuel; Padbury, Jamés F.

doi:10.1172/jci110044

Cited by 147 publications

(99 citation statements)

References 15 publications

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“…Of the label recovered in the surfactant, 69.8% was in phosphatidylcholine. The surfactant is highly surface active and effective as therapy for respiratory distress in premature lambs (12). [14C]-choline (54 Ci/mole) in ethanol was obtained from New England Nuclear.…”

Section: Animalsmentioning

confidence: 99%

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

1982

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Summawre~orted t1 12 may be in error due to continued secretion of isoto~e[3H]-Palmitate labeled natural lamb surfactant and free [14C]-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to % h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent tlIz of phosphatidvlcholine in the whole lung of 6.0 davs. This half-life can be interpreted only as a rough estimate." Appearance of considerable I3H] labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered ['4CI-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered I3HI and Ir4C] were found in pulmonary alveolar macrophages. SpeculationThe prolonged tl/z measured in this study indicates very slow turnover of alveolar phosphatidylcholine and/or considerable reutilization of label and possibly of the entire phosphatidylcholine molecule. The concentration of label in lamellar bodies raises the possibility that alveolar phosphatidylcholine may be degraded and its components utilized for synthesis of new phosphatidylcholine or that alveolar phosphatidylcholine may be absorbed into type-2 alveolar cells and resecreted intact. The finding of [l4Cl labeled phosphatidylcholine in lung homogenate but not in alveolar wash indicates that, even if choline were released by intra-alveolar degradation of surfactant, it is not used to a significant degree for synthesis of new surfactant phosphatidylcholine.The ultimate fate of surfactant phospholipids, once secreted into the alveoli, remains to be defined. Reasonable speculations include: (1) removal via the lymphatic or circulatory systems, (2) metabolism by alveolar macrophages, (3) surface spreading into the airways, or (4) reuptake into pulmonary parenchymal cells with reutilization of all or part of the phospholipid molecule. Estimates of the biologic half-life (tl/z) of surfactant phospholipids in lung parenchyma and in the alveoli have been derived by utilizing radiolabeled phospholipid precursors. The estimated half-life values vary, depending on type of labeled phospholipid precursor used, type of animal studied, and the maturity of the animals. An approximate tlI2 of 16 h has been reported for lung phosphatidylcholine (PC) in adult rats and rabbits, using radiolabeled palmitic acid as a precursor (10,11,19,20). Again using labeled palmitic acid, the biologic ttI2 for alveolar surfactant was estimated to be 54 and 45 h in newborn and adul...

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Section: Animalsmentioning

confidence: 99%

Metabolism of Exogenously Administered Natural Surfactant in the Newborn Lamb

1982

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“…'-' Until recently developmental studies of postnatal left ventricular performance were not possible in newly born preterm animals, because prematurity was associated with a Now, however, acceptable pulmonary function can be maintained with the combined use of surfactant treatment and mechanical ventilation. 10 The purpose of this study was to characterize developmental aspects of left ventricle pump performance and contractility in surfactant-treated preterm lambs and in full-term lambs under conditions simulating those encountered in the neonatal intensive care setting. …”

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confidence: 99%

Left ventricular performance and contractility before and after volume infusion: a comparative study of preterm and full-term newborn lambs.

Baylen¹,

Ogata²,

Ikegami³

et al. 1986

Circulation

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We studied left ventricular performance and contractility after volume loading in lambs at 122 days (group I, n = 9) and 139 days gestational age (group IL, n = 9) and in 8-day-old full-term lambs (group III, n = 7). All were mechanically ventilated; each preterm lamb was treated with surfactant to stabilize pulmonary function and the ductus arteriosus was occluded with an inflated catheter balloon. Cineangiograms, left ventricular and vascular pressures, and the isovolumetric index of contractility, first derivative of left ventricular pressure (dP/dt), were recorded before and after three successive whole blood volume infusions of 10 ml/kg (total 30 ml/kg). The left ventricular enddiastolic volume per kilogram and stroke volume per kilogram increased significantly in all groups after volume infusion; these measurements and heart rate and systemic vascular resistance did not differ significantly between the groups either before or after the infusions. The left ventricular peak dP/dt did not change significantly within the groups during the volume infusions. The left ventricular stroke work was greatest in full-term animals and increased significantly in all groups after volume infusion. Thus, the left ventricles of the preterm and full-term lambs had quantitatively similar Frank-Starling responses and there was no increase in contractility during the infusions of whole blood. However, the left ventricle of the full-term lamb is capable of generating greater stroke work than that of the preterm lamb. These findings may contribute to the understanding of developmental aspects of postnatal circulatory adaptation. Circulation 73, No. 5, 1042No. 5, -1049No. 5, , 1986 IT HAS BEEN suggested that the left ventricle of the premature infant may be less capable than the mature left ventricle of adjusting to transitional circulatory changes required postnatally, such as increasing volume and resistance work.' 2 These conclusions followed from ultrastructural observations and from developmental studies of myocardial contraction in isolated muscle preparations, and from comparative studies of left ventricular performance in the intact fetus and full-term newborn lamb.'-' Until recently developmental studies of postnatal left ventricular performance were not possible in newly born preterm animals, because prematurity was associated with a Now, however, acceptable pulmonary function can be maintained with the combined use of surfactant treatment and mechanical ventilation. 10 The purpose of this study was to characterize developmental aspects of left ventricle pump performance and contractility in surfactant-treated preterm lambs and in full-term lambs under conditions simulating those encountered in the neonatal intensive care setting. Material and methodsWe studied the hemodynamic responses to volume infusions in three groups of preterm and full-term lambs. Group I lambs (n -9) were 122 ± 2 (SD) days gestational age, group II lambs (n = 9) were 139 + 2 days gestational age, and group III (n = 7) consisted of 8 + 3...

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“…When surfactant is administered before the first breath in premature lambs (15,16) and rabbits (24), it will also be distributed relatively uniformly throughout the lungs in the fetal lung fluid. Of interest in this regard are the observations by Jobe et al (25). in an experimental study, and by Enhorning et al (26) and Smyth et al (27), in human studies, that tracheal instillation of surfactant after a period of ventilation may lead to a clinical response of shorter duration than a treatment given at birth.…”

Section: Resultsmentioning

confidence: 99%