Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) mixed with radiopaque tracer was instilled as a plug into the trachea. The lungs were ventilated with a 4-ml tidal volume for 20 breaths at one of two respiratory rates: 20 or 60 breaths/min. The motion of radiodense surfactant was imaged at 30 frames/s with a microfocal X-ray source and an image intensifier. Dynamics of surfactant distribution were quantified for each image by use of distribution statistics and a homogeneity index. We found that the liquid distribution depended on the time to liquid plug rupture, which depends on ventilation rate. At 20 breaths/min, liquid was localized in the gravity-dependent region of the lung. At 60 breaths/min, the liquid coated the airways, providing a more vertically uniform liquid distribution.

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A rat lung model of instilled liquid transport in the pulmonary airways

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.1955 ◽

2001 ◽

Vol 90 (5) ◽

pp. 1955-1967 ◽

Cited By ~ 24

Author(s):

K. J. Cassidy ◽

J. L. Bull ◽

M. R. Glucksberg ◽

C. A. Dawson ◽

S. T. Haworth ◽

...

Keyword(s):

Fluid Transport ◽

Image Intensifier ◽

Lung Model ◽

Exogenous Surfactant ◽

Upper Airways ◽

Liquid Distribution ◽

Liquid Plug ◽

Transport Dynamics ◽

Pulmonary Airways ◽

Forced Air

When a liquid is instilled in the pulmonary airways during medical therapy, the method of instillation affects the liquid distribution throughout the lung. To investigate the fluid transport dynamics, exogenous surfactant (Survanta) mixed with a radiopaque tracer is instilled into tracheae of vertical, excised rat lungs (ventilation 40 breaths/min, 4 ml tidal volume). Two methods are compared: For case A, the liquid drains by gravity into the upper airways followed by inspiration; for case B, the liquid initially forms a plug in the trachea, followed by inspiration. Experiments are continuously recorded using a microfocal X-ray source and an image-intensifier, charge-coupled device image train. Video images recorded at 30 images/s are digitized and analyzed. Transport dynamics during the first few breaths are quantified statistically and follow trends for liquid plug propagation theory. A plug of liquid driven by forced air can reach alveolar regions within the first few breaths. Homogeneity of distribution measured at end inspiration for several breaths demonstrates that case B is twice as homogeneous as case A. The formation of a liquid plug in the trachea, before inspiration, is important in creating a more uniform liquid distribution throughout the lungs.

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Computational Modeling of Surfactant-Laden Liquid Plug Propagation in Capillary Tubes

ASME 2012 10th International Conference on Nanochannels, Microchannels, and Minichannels ◽

10.1115/icnmm2012-73039 ◽

2012 ◽

Author(s):

Metin Muradoglu ◽

Ufuk Olgac

Keyword(s):

Replacement Therapy ◽

Pulmonary Surfactant ◽

Distress Syndrome ◽

Standard Treatment ◽

Exogenous Surfactant ◽

Liquid Plug ◽

Front Tracking Method ◽

Surfactant Replacement ◽

Surfactant Replacement Therapy ◽

Shed Light

Pulmonary surfactant is of essential importance in reducing the surface tension on the liquid film that coats the inner surface of the airways and thus making the lung more compliant. Surfactant-deficiency may result in respiratory distress syndrome (RDS), which is especially common in prematurely born neonates. Surfactant replacement therapy (SRT) is a standard treatment, in which a liquid plug with exogenous surfactant is instilled in the trachea, which subsequently propagates by inspiration and spreads the exogenous surfactant to the airways. The efficacy of the treatment depends on various parameters such as the size of the liquid plug, inspiration frequency and the physical properties of the exogenous surfactant. Unsteady simulations are performed to study surfactant-laden liquid plug propagation using finite difference/front-tracking method in order to shed light on the surfactant replacement therapy.

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Is Less Invasive Surfactant Administration Necessary or “Only” Helpful or Just a Fashion?

American Journal of Perinatology ◽

10.1055/s-0038-1637759 ◽

2018 ◽

Vol 35 (06) ◽

pp. 530-533 ◽

Cited By ~ 4

Author(s):

Ilia Bresesti ◽

Laura Fabbri ◽

Gianluca Lista

Keyword(s):

Large Scale ◽

Exogenous Surfactant ◽

Preterm Neonates ◽

Positive Pressure ◽

Less Invasive ◽

Antenatal Steroids ◽

Surfactant Replacement Therapy ◽

Short And Long Term ◽

Surfactant Administration ◽

A New Technique

AbstractIn the 1990s, the most relevant pillars in the treatment of neonatal respiratory distress syndrome (RDS) have been improvements in ventilation strategies, the introduction of exogenous surfactant replacement therapy, and the use of antenatal steroids. Lately, in addition to the standard INSURE (INtubation–SURfactant administration–Extubation) method to administer surfactant, a new technique has been gaining increasing popularity. It is the so-called less invasive surfactant administration (LISA) method, which has shown promising results in preventing bronchopulmonary dysplasia development and in reducing mortality in preterm neonates. The rationale behind this technique is to avoid positive pressure ventilation and the endotracheal tube, being surfactant delivered through a thin catheter while the neonate is maintained on continuous positive airway pressure. Given the paucity of large-scale randomized trials on LISA method to prove its effects on short- and long-term outcomes, some questions still remain unanswered. Then, uncertainty regarding the feasibility of this maneuver needs to be better clarified before gaining wide acceptance in routine clinical practice. In our report, we aim at hypothesizing the main mechanisms behind the efficacy of LISA, considering it as a single maneuver in a comprehensive approach for RDS management in the delivery room.

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Surfactant Replacement Therapy for Respiratory Distress Syndrome in the Newborn: A Review

Bangladesh Journal of Child Health ◽

10.3329/bjch.v40i1.31552 ◽

2017 ◽

Vol 40 (1) ◽

pp. 26-30

Author(s):

Tahsinul Amin ◽

Mohammod Shahidullah

Keyword(s):

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Pulmonary Hemorrhage ◽

Surfactant Therapy ◽

Respiratory Morbidity ◽

Exogenous Surfactant ◽

Surfactant Replacement ◽

Surfactant Deficiency ◽

Surfactant Replacement Therapy

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in low birth weight premature infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Exogenous surfactant therapy has become well established in newborn infants with respiratory distress. Many aspects of its use have been well evaluated in high-quality trials and systematic reviews. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/ sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This article summarizes the evidence and gives recommendations for the use of surfactant therapy for respiratory distress syndrome (RDS) in newborn.Bangladesh J Child Health 2016; VOL 40 (1) :26-30

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Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury

British Journal of Anaesthesia ◽

10.1093/bja/82.1.81 ◽

1999 ◽

Vol 82 (1) ◽

pp. 81-86 ◽

Cited By ~ 12

Author(s):

A Hartog ◽

G F Vazquez de Anda ◽

D Gommers ◽

U Kaisers ◽

S J Verbrugge ◽

...

Keyword(s):

Mechanical Ventilation ◽

Acute Lung Injury ◽

Lung Injury ◽

Surfactant Therapy ◽

Exogenous Surfactant ◽

Partial Liquid Ventilation ◽

Liquid Ventilation

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Surfactant replacement increases compliance in premature lamb lungs during partial liquid ventilation in situ

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.4.1316 ◽

1998 ◽

Vol 84 (4) ◽

pp. 1316-1322 ◽

Cited By ~ 10

Author(s):

Peter Tarczy-Hornoch ◽

Jack Hildebrandt ◽

Thomas A. Standaert ◽

J. Craig Jackson

Keyword(s):

Force Balance ◽

Exogenous Surfactant ◽

Partial Liquid Ventilation ◽

Liquid Ventilation ◽

Lung Inflation ◽

Surfactant Replacement ◽

Improve Compliance ◽

Alveolar Surface ◽

Force Balance Equation

Treatments available to improve compliance in surfactant-deficient states include exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air-PFC interfaces introduced during PLV compared with TLV, we hypothesized that compliance would be worse during PLV than during TLV. Because surfactant is able to reduce interfacial tension between air and lung as well as between PFC and lung, we further hypothesized that compliance would improve with surfactant treatment before PLV. In excised preterm lamb lungs, we used Survanta for surfactant replacement and perflubron as the PFC. Compliance during PLV was intermediate between TLV and gas inflation, both with and without surfactant. Surfactant improved compliance during PLV, compared with PLV alone. Because of the force-balance equation governing the behavior of immiscible droplets on liquid surfaces, we predict that PFC droplets spread during PLV to cover the alveolar surface in surfactant-deficient lungs during most of lung inflation and deflation but that the PFC would retract into droplets in surfactant-sufficient lungs, except at end inspiration.

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Effects of hemoglobin and cell membrane lipids on pulmonary surfactant activity

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.4.1434 ◽

1987 ◽

Vol 63 (4) ◽

pp. 1434-1442 ◽

Cited By ~ 130

Author(s):

B. A. Holm ◽

R. H. Notter

Keyword(s):

Surface Tension ◽

Erythrocyte Membrane ◽

Membrane Lipids ◽

Dynamic Compression ◽

Lung Surfactant ◽

Lung Mechanics ◽

Exogenous Surfactant ◽

Dynamic Surface ◽

Surfactant Replacement ◽

Surfactant Replacement Therapy

These experiments characterize the effects of hemoglobin and erythrocyte membrane lipids on the dynamic surface activity and adsorption facility of whole lung surfactant (LS) and a calf lung surfactant extract (CLSE) used clinically in surfactant replacement therapy for the neonatal respiratory distress syndrome (RDS). The results show that, at concentrations from 25 to 200 mg/ml, hemoglobin (Hb) increased the minimum dynamic surface tension of LS or CLSE mixtures (0.5 and 1.0 mumol/ml) from less than 1 to 25 dyn/cm on an oscillating bubble apparatus at 37 degrees C. Similarly, erythrocyte membrane lipids (0.5–3 mumol/ml) also prevented LS and CLSE suspensions (0.5–2.0 mumol/ml) from lowering surface tension below 19 dyn/cm under dynamic compression on the bubble. Surface pressure-time adsorption isotherms for LS suspensions (0.084 and 0.168 mumol phospholipid/ml) were also adversely affected by Hb (0.3–2.5 mg/ml), having a slower adsorption rate and magnitude. Significantly, these inhibitory effects of Hb and membrane lipids could be abolished if LS and CLSE concentrations were raised to high levels. In complementary physiological experiments, instillation of Hb, membrane lipids, or albumin into excised rat lungs was shown to cause a decrease in pressure-volume compliance. This decreased compliance was most prominent in lungs made partially surfactant deficient before inhibitor delivery and could be reversed by supplementation with active exogenous surfactant. Taken together, these data show that molecular components in hemorrhagic pulmonary edema can biophysically inactivate endogenous LS and adversely affect lung mechanics. Moreover, exogenous surfactant replacement can reverse this process even in the continued presence of inhibitor molecules and thus has potential utility in therapy for adult as well as neonatal RDS.

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Effects of exogenous surfactant supplementation and partial liquid ventilation on acute lung injury induced by wood smoke inhalation in newborn piglets

Critical Care Medicine ◽

10.1097/01.ccm.0000059312.90697.32 ◽

2003 ◽

Vol 31 (4) ◽

pp. 1166-1174 ◽

Cited By ~ 19

Author(s):

Mei-Jy Jeng ◽

Yu Ru Kou ◽

Ching-Chung Sheu ◽

Betau Hwang

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Smoke Inhalation ◽

Wood Smoke ◽

Exogenous Surfactant ◽

Partial Liquid Ventilation ◽

Liquid Ventilation ◽

Newborn Piglets

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Interaction of exogenous and endogenous surfactant: spreading-rate effects

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.2.750 ◽

1995 ◽

Vol 78 (2) ◽

pp. 750-756 ◽

Cited By ~ 42

Author(s):

J. B. Grotberg ◽

D. Halpern ◽

O. E. Jensen

Keyword(s):

Surface Tension ◽

Spreading Rate ◽

Exogenous Surfactant ◽

Concentration Increase ◽

Delivery Times ◽

Surfactant Replacement Therapy ◽

Rate Effects ◽

Therapeutic Mechanism ◽

Air Liquid Interface ◽

Published Paper

The spreading rate of an exogenous surfactant monolayer due to surface tension gradients is examined by using our previously reported theoretical analysis, with particular attention given to the effects of endogenous surfactant. It is found that the presence of an endogenous surfactant reduces the spreading rate of exogenous surfactant and that, in certain circumstances, the spreading may be halted. A recently published paper (F. F. Espinosa, A. H. Shapiro, J. J. Fredberg, and R. D. Kamm. J. Appl. Physiol. 75: 2028–2039, 1993) reaches the opposite conclusion about the effect of endogenous surfactant, i.e., that the presence of an endogenous surfactant increases the spreading rate of the exogenous surfactant. This communication discusses the relevant issues associated with these different results and what the implications may be for surfactant replacement therapy. It is found that the endogenous surfactant, which is ahead of the advancing exogenous surfactant front, undergoes a concentration increase due to surface area compression of the air-liquid interface. Hence the spreading exogenous surfactant can raise surfactant concentrations in regions distal to its own location, and this is a previously unrecognized potential therapeutic mechanism of instilled surfactants. After initial instillations of intratracheal boluses of exogenous surfactant, additional surfactant may better reach the desired target site if delivered by aerosol. Predictions of surfactant and piggy-backed drug-delivery times through the lung are also discussed.

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