A synthetic surfactant based on a poly-Leu SP-C analog and phospholipids: effects on tidal volumes and lung gas volumes in ventilated immature newborn rabbits

2003 ◽  
Vol 95 (5) ◽  
pp. 2055-2063 ◽  
Author(s):  
Jan Johansson ◽  
Margareta Some ◽  
Britt-Marie Linderholm ◽  
Andreas Almlén ◽  
Tore Curstedt ◽  
...  
Keyword(s):  
Palmitic Acid ◽  
Distress Syndrome ◽  
Newborn Infants ◽  
Surfactant Protein ◽  
Synthetic Surfactant ◽  
Airway Epithelial ◽  
Phosphoryl Choline ◽  
Gas Volume ◽  
Artificial Surfactant ◽  
Newborn Animals

Available surfactants for treatment of respiratory distress syndrome in newborn infants are derived from animal lungs, which limits supply and poses a danger of propagating infectious material. Poly-Val→poly-Leu analogs of surfactant protein (SP)-C can be synthesized in large quantities and exhibit surface activity similar to SP-C. Here, activity of synthetic surfactants containing a poly-Leu SP-C analog (SP-C33) was evaluated in ventilated premature newborn rabbits. Treatment with 2.5 ml/kg body wt of 2% (wt/wt) SP-C33 in 1,2-dipalmitoyl- sn-3-glycero phosphoryl choline (DPPC)-1-palmitoyl-2-oleoyl- sn-3-glycero phosphoryl choline (POPC)-1-palmitoyl-2-oleoyl- sn-3-glycero phosphoryl glycerol (POPG), 68:0:31, 68:11:20, or 68:16:15 (wt/wt/wt) suspended at 80 mg/ml gave tidal volumes (Vt) of 20-25 ml/kg body wt, with an insufflation pressure of 25 cmH2O and no positive end-expiratory pressure (PEEP), comparable to the Vt for animals treated with the porcine surfactant Curosurf. Nontreated littermates had a Vt of ∼2 ml/kg body wt. The Vt for SP-C33 in DPPC-egg phosphatidylglycerol-palmitic acid [68:22:9 (wt/wt/wt)], DPPC-POPG-palmitic acid [68:22:9 (wt/wt/wt)], and DPPC-POPC-POPG [6:2:2 (wt/wt/wt)] was 15-20 ml/kg body wt. Histological examination of lungs from animals treated with SP-C33-based surfactants showed incomplete, usually patchy air expansion of alveolar spaces associated with only mild airway epithelial damage. Lung gas volume after 30 min of mechanical ventilation were more than threefold larger in animals treated with Curosurf than in those receiving SP-C33 in DPPC-POPC-POPG, 68:11:20. This difference could be largely counterbalanced by ventilation with PEEP (3-4 cmH2O). An artificial surfactant based on SP-C33 improves Vt in immature newborn animals ventilated with standardized peak pressure but requires PEEP to build up adequate lung gas volumes.

Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome

2008 ◽  
Vol 104 (4) ◽  
pp. 1101-1108 ◽  
Author(s):  
Andreas Almlén ◽  
Guido Stichtenoth ◽  
Bim Linderholm ◽  
Marie Haegerstrand-Björkman ◽  
Bengt Robertson ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Surfactant Protein ◽  
Synthetic Surfactant ◽  
Positive End Expiratory Pressure ◽  
Natural Surfactant ◽  
Alveolar Stability ◽  
The Individual ◽  
Artificial Surfactant

Modified natural surfactant preparations, used for treatment of respiratory distress syndrome in premature infants, contain phospholipids and the hydrophobic surfactant protein (SP)-B and SP-C. Herein, the individual and combined effects of SP-B and SP-C were evaluated in premature rabbit fetuses treated with airway instillation of surfactant and ventilated without positive end-expiratory pressure. Artificial surfactant preparations composed of synthetic phospholipids mixed with either 2% (wt/wt) of porcine SP-B, SP-C, or a synthetic poly-Leu analog of SP-C (SP-C33) did not stabilize the alveoli at the end of expiration, as measured by low lung gas volumes of ∼5 ml/kg after 30 min of ventilation. However, treatment with phospholipids containing both SP-B and SP-C/SP-C33 approximately doubled lung gas volumes. Doubling the SP-C33 content did not affect lung gas volumes. The tidal volumes were similar in all groups receiving surfactant. This shows that SP-B and SP-C exert different physiological effects, since both proteins are needed to establish alveolar stability at end expiration in this animal model of respiratory distress syndrome, and that an optimal synthetic surfactant probably requires the presence of mimics of both SP-B and SP-C.

scholarly journals Annexin A2 Mediates Mycoplasma pneumoniae Community-Acquired Respiratory Distress Syndrome Toxin Binding to Eukaryotic Cells

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Sudha R. Somarajan ◽  
Fadi Al-Asadi ◽  
Kumaraguruparan Ramasamy ◽  
Lavanya Pandranki ◽  
Joel B. Baseman ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Mammalian Cells ◽  
Distress Syndrome ◽  
Protein A ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Annexin A2 ◽  
Toxin Binding ◽  
Cards Toxin

ABSTRACT Mycoplasma pneumoniae synthesizes a novel human surfactant protein A (SP-A)-binding cytotoxin, designated community-acquired respiratory distress syndrome (CARDS) toxin, that exhibits ADP-ribosylating and vacuolating activities in mammalian cells and is directly linked to a range of acute and chronic airway diseases, including asthma. In our attempt to detect additional CARDS toxin-binding proteins, we subjected the membrane fraction of human A549 airway cells to affinity chromatography using recombinant CARDS toxin as bait. A 36-kDa A549 cell membrane protein bound to CARDS toxin and was identified by time of flight (TOF) mass spectroscopy as annexin A2 (AnxA2) and verified by immunoblotting with anti-AnxA2 monoclonal antibody. Dose-dependent binding of CARDS toxin to recombinant AnxA2 reinforced the specificity of the interaction, and further studies revealed that the carboxy terminus of CARDS toxin mediated binding to AnxA2. In addition, pretreatment of viable A549 cells with anti-AnxA2 monoclonal antibody or AnxA2 small interfering RNA (siRNA) reduced toxin binding and internalization. Immunofluorescence analysis of CARDS toxin-treated A549 cells demonstrated the colocalization of CARDS toxin with cell surface-associated AnxA2 upon initial binding and with intracellular AnxA2 following toxin internalization. HepG2 cells, which express low levels of AnxA2, were transfected with a plasmid expressing AnxA2 protein, resulting in enhanced binding of CARDS toxin and increased vacuolization. In addition, NCI-H441 cells, which express both AnxA2 and SP-A, upon AnxA2 siRNA transfection, showed decreased binding and subsequent vacuolization. These results indicate that CARDS toxin recognizes AnxA2 as a functional receptor, leading to CARDS toxin-induced changes in mammalian cells. IMPORTANCE Host cell susceptibility to bacterial toxins is usually determined by the presence and abundance of appropriate receptors, which provides a molecular basis for toxin target cell specificities. To perform its ADP-ribosylating and vacuolating activities, community-acquired respiratory distress syndrome (CARDS) toxin must bind to host cell surfaces via receptor-mediated events in order to be internalized and trafficked effectively. Earlier, we reported the binding of CARDS toxin to surfactant protein A (SP-A), and here we show how CARDS toxin uses an alternative receptor to execute its pathogenic properties. CARDS toxin binds selectively to annexin A2 (AnxA2), which exists both on the cell surface and intracellularly. Since AnxA2 regulates membrane dynamics at early stages of endocytosis and trafficking, it serves as a distinct receptor for CARDS toxin binding and internalization and enhances CARDS toxin-induced vacuolization in mammalian cells.

Passive compliance of total respiratory system in preterm newborn infants with respiratory distress syndrome

1988 ◽  
Vol 112 (5) ◽  
pp. 778-781 ◽  
Author(s):  
Eduardo Dreizzen ◽  
Marek Migdal ◽  
Jean-Paul Praud ◽  
Jean-Francois Magny ◽  
Michel Dehan ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Respiratory System ◽  
Distress Syndrome ◽  
Newborn Infants ◽  
Preterm Newborn ◽  
Passive Compliance

Synthetic surfactant scavenges oxidants and protects against hyperoxic lung injury

1994 ◽  
Vol 77 (3) ◽  
pp. 1217-1223 ◽  
Author(s):  
A. J. Ghio ◽  
P. J. Fracica ◽  
S. L. Young ◽  
C. A. Piantadosi
Keyword(s):  
Thiobarbituric Acid ◽  
Cetyl Alcohol ◽  
Synthetic Surfactant ◽  
Active Components ◽  
Lung Weight ◽  
Hyperoxic Lung Injury ◽  
Surface Active ◽  
Artificial Surfactant

Injury and mortality after exposure to 100% oxygen can be diminished by surfactants that may operate by mechanisms other than those responsible for surface tension effects. We tested the hypotheses that 1) synthetic surfactant and its components function as antioxidants in vitro and 2) decrements in hyperoxic injury after treatment with a surfactant and its components are associated with decreases in oxidative stress to the lung. A synthetic surfactant (Exosurf) and its non-surface-active components tyloxapol and cetyl alcohol were incubated in an iron-containing hydroxyl radical-generating system to determine their abilities to prevent oxidation of deoxyribose. Doses of tyloxapol, cetyl alcohol, and artificial surfactant diminished the absorbance of thiobarbituric acid-reactive products of deoxyribose. Similarly, tyloxapol, cetyl alcohol, and the surfactant decreased hydroxylated products of salicylate in the same system. Rats were instilled intratracheally with saline, tyloxapol, tyloxapol plus cetyl alcohol, or artificial surfactant and immediately exposed to air or 100% oxygen. After 61 h of oxygen exposure, pleural fluid volume and wet-to-dry lung weight ratios were decreased in animals treated with surfactant and/or its components. There were also decrements in thiobarbituric acid-reactive products of lung tissue. In separate experiments, mean survival of saline-treated rats exposed to 100% oxygen was 67.3 +/- 8.1 h and > 96 h for rats given the surfactant or its components. We conclude that tyloxapol, cetyl alcohol, and Exosurf can function as antioxidants in vitro and their in vivo instillation is associated with reduction in measures of hyperoxic injury, oxidized tissue products, and mortality.

PHYSIOLOGY OF RESPIRATION IN NEWBORN INFANTS AND IN THE RESPIRATORY DISTRESS SYNDROME

PEDIATRICS ◽  
1959 ◽  
Vol 24 (6) ◽  
pp. 1069-1101
Author(s):  
L. Stanley James
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Newborn Infants ◽  
Clinical Signs ◽  
Birth Asphyxia ◽  
The Body ◽  
Normal Lung ◽  
Term Infants ◽  
Lung Expansion

To improve our understanding of the respiratory distress syndrome, the importance of early examination of the infant, preferably at delivery, cannot be overemphasized. An attempt should be made to estimate clinically the degree of birth asphyxiation by a method such as the Apgar Score. The nature of respirations as well as the rate should be noted, particularly retractions and grunting. Decreased response to stimuli or poor tone, and a low blood pressure are significant signs. In this review, a number of comparisons have been drawn, including evidence from adult medicine or animal experiments. While these may appear unrelated, irrelevant or unduly speculative, they have been introduced for several purposes: to draw attention to aspects of the syndrome other than respiratory distress; to acquaint the general reader with more recent physiology which is deemed pertinent; and to emphasize the importance of relating one system to another, especially respiration to circulation. Many of the studies of respiratory function point to cardiac as well as pulmonary failure, notably the need for oxygen in the presence of a normal tidal and increased minute volume. Other circumstantial evidence of cardiac failure is abundant. Asphyxia appears to play a central role, affecting almost every system in the body and every phase of metabolism. It is probably responsible for the normal or low venous pressures occurring with a failing myocardium. It also accounts for the higher incidence of respiratory distress in the smaller prematures who are unable to achieve and maintain normal lung expansion. The syndrome is uncommon in larger full-term infants and in these instances is associated with obstetrical complications causing more severe degrees of birth asphyxia. The clinical picture includes a number of variations depending upon whether respiratory depression or symptoms relating to the central nervous or gastrointestinal systems predominate. Nevertheless, diagnosis of the respiratory distress syndrome should rely not on the presence or absence of membranes at necropsy, but rather on the history, symptoms and clinical signs. Inasmuch as asphyxia is not a disease, it would seem more logical to regard the syndrome as a failure in adaptation to extrauterine life. Failure to comprehend the many adaptations which newborn infants must make, both cardiopulmonary and biochemical, together with a narrow view centering only around the hyaline membranes, have for so many years cloaked this syndrome with mystery. Physiologic measurements in sick infants are difficult, and many of the determinations and calculations arduous. Some of the studies require confirmation, and others remain to be done, employing new or improved technics which are free from disadvantages of older methods. Because of many variables, caution should be exercised in drawing conclusions from a small number of cases. Early pioneering work has contributed greatly and has paved the way for future investigations. The value of serial studies correlated with careful clinical observations in order that the precise nature of a dynamic process may be more fully revealed has been clearly shown.

Determinants of forced expiratory flows in newborn infants

1982 ◽  
Vol 53 (5) ◽  
pp. 1220-1227 ◽  
Author(s):  
L. M. Taussig ◽  
L. I. Landau ◽  
S. Godfrey ◽  
I. Arad
Keyword(s):  
Newborn Infants ◽  
Cross Sectional Area ◽  
Physiological Data ◽  
Sectional Area ◽  
Older Children ◽  
Cross Sectional ◽  
Thoracic Gas Volume ◽  
Residual Capacity ◽  
The Cross ◽  
Gas Volume

Maximal flows at functional residual capacity (VmaxFRC) from partial expiratory flow-volume (PEFV) curves (achieved with rapid compression of the chest) were obtained on 11 healthy newborn babies. Mean VmaxFRC, size corrected by dividing absolute values by measured thoracic gas volume, was 1.90 TGV's/s. Specific upstream conductances were high, and the cross-sectional area of the flow-limiting segment was estimated to be approximately 0.30 cm2 in the three infants on whom recoil pressures at FRC were also measured. The cross-sectional area of the major bronchi in the neonate is approximately 0.26–0.30 cm2. PEFV curves were convex to the volume axis. Many of the neonates increased their flows while breathing a helium-oxygen gas mixture. These results suggest 1) size-corrected flows are higher in the neonate than in older children or adults; 2) the site of the flow-limiting segment at FRC during maximal expiratory maneuvers is in large proximal airways, similar to the adult; and 3) the relationship of airway size to parenchymal size may be similar in neonates and adults or, in fact, airways may be larger, relative to parenchyma, in neonates. These physiological data do not support the hypothesis, based on pathological studies, that peripheral airways are disproportionately smaller (when compared with central airways) in infants than in adults.

Sign in / Sign up

Export Citation Format

Share Document