The effect of arnafant surfactant on respiratory distress syndrome in rats

doi:10.21203/rs.3.rs-1421357/v1

Download PDF

Research Article

The effect of arnafant surfactant on respiratory distress syndrome in rats

https://doi.org/10.21203/rs.3.rs-1421357/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objectives Acute respiratory distress syndrome (ARDS) is occurred by disruption of alveolar-capillary membrane and associated with an inflammation process. In the present study, the effect of arnafant surfactant on RDS in rats was compared to curosurf.

Methods RDS was induced in male Wister rats by surfactant washout using 10 times lung lavage with 3 ml saline at 37^oC through an intra-tracheal cannula after anesthetized with intrapritonal administration of 60 mg thiopental Na while animals were ventilated. Then chest was opened and stepwise increasing volume of air was administered and withdrawer from the lung while lung pressure was monitored and lung compliance was determined using lung volume-pressure curve. Total and differential white blood cells (WBC) as well as oxidative stress markers in the blood and bronco-alveolar lavage (BALF) were also examined. The study was performed in 4 groups (n=10 in each group) of rats including control and RDS, both traded with saline, RDS treated with arnafant and RDS treated with curosurf (2.5 ml contained 6.25 mg surfactant for both drugs).

Results The value of lung compliance in RDS group was significantly reduced compared to control group (P<0.001). However, in RDS group treated with arnafant, lung compliance was significantly increased compared to both untreated and to curosurf treated RDS groups (P<0.001 for both cases). Total and differential WBC counts in the blood of RDS group were significantly increased compared to the control group but in RDS group treated with arnafant, total WBC, and lymphocyte counts were significanty decreased compared to untreated RDS group (P<0.01-P<0.001). In the BALF of RDS group treated with curosurf, total and differential WBC were significantly increased but in RDS group treated with arnafant, only total WBC, eosinophil and lymphocyte counts were significanty increased compared to the control group (P<0.01-P<0.001). In the BALF, lung tissue and serum of untreated RDS group, all oxidative stress markers were significantly changed compared to the control group but in arnafant treated RDS group all markers and in curosurf treated RDS group, only thiol level and CAT activity in the BALF as well as MDA and thiol levels both in the lung tissue and serum were significanty improved compared to untreated RDS group (P<0.05-P<0.001).

Conclusion Treatment of RDS rats with arnafant significantly improved lung compliance as well as lung and systemic inflammation and oxidative stress and the effect of this surfactant drug was significantly higher than curosurf.

Respiratory distress syndrome

Surfactant

Arnafant

Curosurf

Compliance

Inflammation

Oxidative stress

Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory response characterized by damage of the vesicular-capillary membrane [1]. ARDS was first described in humans about 50 years ago during the Vietnam War as "shock lung" or "DaNang lung" [2], which can be caused by a number of factors and can lead to hospitalization.

Acute lung injury (ALI) and ARDS account for 10 to 15% of to the intensive care unit admission [3, 4]. Despite advances in intensive care, respiratory distress syndrome (RDS) and lung injury are a major cause of death among patients. The only effective intervention for these patients is low-volume assisted ventilation by a ventilator [5, 6]. There has been no significant reduction in ARDS-related mortality since 1994 [3]. Direct factors to the lung parenchyma (aspiration, pneumonia or smoke inhalation) or indirect lung factors (sepsis, trauma, pancreatitis, burn injury, blood transfusion) are the main causes of acute lung injury and acute RDS, which also cause an acute systemic inflammatory response [7].

Clinical signs of ARDS include refractory hypoxemia, non-cardiogenic edema, and decreased lung elasticity. Impairment of lung surfactant is a major cause of RDS, and acute clinical manifestations usually occur within 24 to 48 hours after the onset of insult [2, 6, 8, 9]. As lung damage progresses, hemodynamic abnormalities become apparent; pulmonary vascular resistance increases and cardiac output and pulmonary artery pressure also increase. In the absence of heart disease, a decrease in mean arterial pressure (MAP) due to decreased systemic vascular resistance may also occur in ALI/ARDS patients with the development of a systemic inflammatory response [10].

Lung surfactants are secreted by type II alveolar cells, and their constituents are phospholipids, surfactant proteins, and neutral lipids. Surfactant reduces alveolar surface tension and prevents alveolus from overlapping or atelectasis. In addition, the surfactant helps to open the smaller respiratory tract and improves mucus secretion. Furthermore, surfactant-specific proteins are part of the innate immune defense mechanisms of the lung. Lung surfactant changes have been described in a number of respiratory diseases. Therefore, of the common treatments for RDS is the use of surfactants.

Curosurf (Alpha, Chiesi Farmaceutici, and Parma, Italy) is a lung surfactant produced from chopped pork extract, exposed to chloroform/methanol, and finally obtained by liquid gel filtration chromatography. It contains the highest amount of phospholipids (PLs) with the lowest size distribution and also contains the highest amount of plasmalogens [11], but arnafant is made by Artajan Pharmed Company. Surfactant deficiency in premature animals causes neonatal RDS. The study of amniotic fluid-derived surfactants made it possible to assess human fetal lung maturation (FLM) and used exogenous surfactants as a preventive care drug in the intensive care unit [12]. The potential role of surfactant in the preservation of terminal bronchi was first described in 1970 by McLem et al., [13]. Surfactant is a protective barrier against surface tension and invasion of microorganisms into the lungs [14].

Although several drug strategies have been successful in animal studies [8, 15, 16], but, the inconsistency between animal and clinical studies may be due to the heterogeneity of the ALI/ARDS distribution, severity, causes, and pathophysiological timing of the syndrome. Given the limited treatment options, the complexity of the disease, and the lack of coordination between animal and clinical studies, it is important to select the ALI/ARDS animal model to evaluate new therapies. The variables used to assess the similarity of ALI/ARDS animal models to clinical disease are: physiology, mechanism, pathology and pathophysiology; technical cases and potential applications are also considered [1]. It is difficult to achieve an experimental design that measures the full range of potential diagnostic parameters in an animal model of ARDS. In 2011, a committee formed by the American Thoracic Society (ATS) published a report proposing a list of effective indicators that should include the main features of ARDS resulting from animal testing important indicators including: (a) evidence of tissue damage and pulmonary cell population, (b) capillary-alveolar change, (c) leukocyte-induced inflammatory response, and (d) dysfunctional physiological changes of the lung [17].

To diagnose ARDS in an animal model, there must be 3 of these 4 criteria. In addition, the ATS Committee has defined the following classification findings for each criterion. For example, when evaluating histological evidence, the accumulation of neutrophils in the vesicular or interstitial space and the thickening of the vesicular walls should be considered, while atelectasis and hemorrhage were less important factors [17]. The ATS Committee has suggested that in order to confirm the diagnosis of ARDS in research animals, there must be at least one "very relevant" point in 3 of the 4 main criteria.

In various animal species, including mice, surfactant disorder resulted in repeated lung lavage of lung tissue, which is very similar to ARDS [18, 19]. Atelectasis and protein leakage have also been observed in this syndrome [18, 20]. These changes lead to impaired respiratory gas exchange [20]. Several studies have shown that these tissue complications are reduced following LSF administration [18, 20]. Oxidative stress, or nitrosation, is a condition characterized by an increase in the level of reactive oxygen species. It is known as one of the most important features not only in the aging process but also in many acute and chronic diseases. The production of reactive oxygen species (ROS) in lung infection plays an important role in the development of ARDS as well as several physiological and pathophysiological conditions are related to the modification of oxidative-antioxidant cells [21].

In this study, the effect of two types of surfactants: including alpha or curosurf, which is used to treat infants with RDS and the commonly secreted type of arnafant on experimental RDS in rats were examined. The aim of this study was to evaluate the effect of arnafant surfactant in comparison with curosurf on acute RDS and to measure lung and systemic inflammation and oxidative stress.

Study groups

Forty Wistar rats (males weighing 240±10 g) were purchased from the animal house of Mashhad University of Medical Sciences and kept in groups of 10 in separate ventilation cages with free access to food and water in the same place. The animals were kept at 22±2 °C, 54±2% relative humidity and 12 hours of light/dark cycle. Rats were randomly studied in the following 4 groups:

1- Control group

2- RDS group caused by saline lavage and treated with saline

3- RDS group treated with curosurf

4- RDS group treated with arnafant

Surfactant (2 ml, containing 6.25 mg of surfactant) and saline were administered through tracheal cannula into the lung.

RDS induction

Respiratory distress syndrome was induced by washing the lung surfactant by lung lavage with 3 ml saline at 37 °C for ten times, after anesthetized animals (using thiopental sodium, 60 mg/kg) and tracheostomy. Ten consecutive lung lavages were performed with 2 min intervals in 4 first and 5 min intervals in 6 last washes.

After 10 lung wash one-hour time period was allowed to ensure the induction of RDS (the end of this stage is called pre-instillation). Air, saline and drugs (curosurf and arnafant, during a 10 minutes' time period) were administered through three-way tape connected to the cannula inside the trachea at a 45º angle in three straight directions, lateral left and right (this stage is called post-instillation) [22-24]. In the interval between each lavage and during the whole test period, animals were ventilated with room air at a respiratory rate of 50 beats/minute and a tidal volume of 1.2 ml/100 g of animal weight (Palmer ventilator, UK).

Measured criteria

Measurement of lung compliance

The animal’s chest was opened so that the lungs were not damaged. To measure lung compliance, 2 ml volumes of air was injected for 5 seconds and after 5 minutes, the static lung pressure was measured using a transducer connected to the powerLab (Power Lab 8/30, ML870, AD Instruments, Australia), [22, 23]. This procedure was repeated until the lungs pressure reaches 30 mm Hg, at which point the lungs are almost completely filled with air (inflation maneuver). After this step, 2 ml of air was drawn from the lungs until the lung pressure reaches zero with the same pattern (deflation maneuver). The volume-pressure curve of the lung was then plotted and lung compliance was determined [22, 23].

Total and differential WBC in the bronchial-alveolar lavage fluid and blood

Five ml of peripheral blood is prepared from the heart of animals. Bronchial-alveolar lavage fluid (BALF) was prepared by the lungs and airways lavaged for 4 times with 5 ml of normal saline (each time with 1 ml). Total and differential white blood cells (WBC) counts in the blood and the BALF were don according previous reports [25, 26].

Oxidant and antioxidant markers in the bronchial-alveolar lavage fluid and serum

BALF was centrifuged at 2500 revolution per minute (rpm) for 10 minutes at 37 °C. Blood was also centrifuged at 2000 rpm for 10 min, and serum was collected. The BALF supernatant and serum were stored at -70 °C until measurement of oxidative stress markers. Oxidants and antioxidants including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and thiol were measure according previous reports [25, 26].

Lung pathological evaluation

At the end of the study animals were sacrificed, left lung was removed and place it in 10% formalin buffer. After 7 days, lung tissues were cleaned using Autotechnicon device, pass it into formalin 70%. and paraffin blokes and tissue slices (4µm) were prepared, and after staining with hematoxylin-eosin, lung pathological evaluation was performed according a previous report [27].

Statistical analysis

Statistical calculations are performed by instat software (GraphPad Software, Inc, La Jolla, USA). All data are presented as mean±SEM. Data from control rats, curosurf-treated RDS, and arnafant-treated RDS were compared using ANOVA and Tukey's post hoc test [28]. Statistical significance was considered at P<0.5 or lower.

The effect of RDS ant surfactant treatment on lung compliance

In the RDS group, lung volume-pressure curve was shifted to the right compared to the control group and returned to control value in the curosurf treated RDS group. However, in the arnafant treated group, it further shifted to the left even compared to control group (Fig. 1). Lung compliance in the RDS group significantly reduced compared to the control group (P<0.001) but in RDS group treated with arnafant, it significantly increased compared to untreated RDS and RDS treated group with curosurf (P<0.001 for both cases), (Fig. 2).

The effect of RDS ant surfactant treatment on lung inflammation

In the BALF of the RDS group treated with curosurf, total and all differential WBC were significantly increased compared to the control group (P<0.01 for monocyte and P<0.001 for other cases) but in the RDS group treated with arnafant, only total WBC, eosinophil and lymphocyte counts were significanty increased (P<0.01 for lymphocyte and P<0.001 for other two cases). Also, in the RDS group treated with arnafant, total and all differential WBC counts were significanty lower than those of the RDS group treated with curosurf (P<0.05 to P<0.001), (Fig. 3).

The effect of RDS ant surfactant treatment on lung oxidative stress

In the BALF of the untreated RDS group, MDA level, was significantly increased but CAT, SOD and thiol levels were significantly reduced compared to the control group (P<0.01 for thiol and P<0.001 for other cases). All oxidant and anti-oxidant markers in the BALF and lung tissue of the RDS group treated with arnafant were significantly improved but in the RDS group treated with curosurf, only MDA and thiol levels in the lung tissue and thiol and CAT levels in the BALF were significanty improved compared to the untreated RDS group (P<0.05 to P<0.001), (Figs. 4 and 5).

The effect of RDS ant surfactant treatment on lung pathological changes

Lung photographs specimens in all studied groups were shown in Fig. 6. The lung pathological scores were not statistically different among different studied groups (Fig. 7).

The effect of RDS ant surfactant treatment on systemic inflammation and oxidative stress

Total and differential WBC counts in the blood of the RDS group were significantly increased compared to the control group (P<0.01 for eosinophil and P<0.001 for other cases). In the arnafant treated group, total WBC, and lymphocyte counts were significanty decreased compared to the untreated RDS (P<0.001 for both cases), (Fig. 8). In the serum of the untreated RDS group, MDA level, was significantly increased but CAT, SOD and thiol levels were significantly reduced compared to the control group (P<0.01 for thiol and P<0.001 for other cases). All oxidant and anti-oxidant markers in the serum of the RDS group treated with arnafant were significantly improved but in the RDS group treated with curosurf, only MDA and thiol levels in the serum were significanty improved compared to untreated RDS group (P<0.05 to P<0.001), (Fig. 9).

ARDS is an acute inflammatory reaction that causes damage to the vesicular-capillary membrane [1]. Despite many advances in intensive care, RDS and lung injury are one of the leading causes of death among patients. Clinical signs of ARDS include persistent hypoxemia, non-cardiogenic edema and decreased lung elasticity. Impairment of lung surfactant is a major cause of RDS, and acute clinical manifestations usually occur within 24 to 48 hours [2, 6, 8, 9]. Therefore, administration of surfactant is one of the main treatments for this syndrome.

In this study, the effect of arnafant, which is a natural surfactant, was compared with a known type of surfactant, curosurf on the RDS model in rats. In the RDS model in rats, the lung pressure-volume curve was shifted to the right and lung compliance was decreased compared to the control (healthy) group. The results showed that treatment of RDS model in rats with arnafant caused left-ward shift of lung pressure-volume curve and increased compliance compared to the RDS group and compared to the group treated with curosurf and even to the (healthy) control group. In the RDS group treated with curosurf, although the volume pressure curve of the lung was deviated to the left compared to the RDS group and the compliance was increased, however, these changes were significantly less than those treated with arnafant.

Total and differential WBC in the BALF of the untreated and treated RDS groups showed an increase compared to the control group, indicating the presence of a pulmonary inflammatory process in the animal model of RDS, which is confirmed by previous studies. However, total and differential WBC in the RDS group treated with arnafant were significantly lower than the RDS group treated with curosurf, indicating the inhibitory effect of arnafant on the inflammatory process resulting from RDS. Previous studies have shown the anti-inflammatory effect of some types of surfactants, which confirms the results of this study [29, 30].

The level of MDA in the BALF and lung tissue of untreated RDS groups were also increased and the antioxidant factors decreased, indicating oxidative stress in the lungs due to RDS process. Previous studies have also shown the development of oxidative stress in the lungs due to RDS too [31], which confirms the results of the present study. Treatment of RDS model with arnafant improved all oxidant and antioxidant agents and treatment with curosurf improved some of them. This part of the results shows the inhibitory effect of arnafant on RDS-induced lung oxidative stress, which was significantly greater than curosurf.

The results of the present study did not show significant pathological changes in the lung of the RDS model and in treatment groups with curosurf, and arnafant. However, a previous study showed significant pathological changes in an animal model of RDS [31], possibly due to inflammatory and oxidative stress process [29–31]. The discrepancy between the results of the current study and previous studies regarding lung pathological changes in animal model of RDS is perhaps due to differences in the methods of RDS induction.

Total and differential WBC in the blood of untreated and treated RDS groups were increased compared to the control group indicating the induction of a systemic inflammatory trend in the animal model of RDS. Some previous studies have also reported systemic inflammation in RDS [29, 30], which confirms the results of the present study. Total and differential WBC in the blood of the RDS group treated with arnafant were significantly lower than the RDS group treated with curosurf which showed the inhibitory effect of arnafant on the systemic inflammatory process resulting from RDS. Previous studies have shown the inhibitory effect of some types of surfactants on systemic inflammation, which confirms the results of the present study [29, 30].

Increased MDA and decreased antioxidant markers in the serum of untreated RDS groups also indicate systemic oxidative stress that has been reported in previous studies [31] and therefore confirms the results of this study. Improvement of all oxidant and antioxidant agents in arnafant-treated RDS group and improvement of some of them in curosurf-treated group indicates the inhibitory effect of arnafant on RDS-induced lung oxidative stress, which was more prominent in curosurf treated group.

Treatment of RDS rats with arnafant significantly improved lung compliance as well as lung and systemic inflammation and oxidative stress and the effect of this surfactant drug was significantly higher than curosurf indicating it promising therapeutic effect on RDS. However, to use this agent in clinical practice further clinical study should be performed.

ALI: Acute lung injury, ARDS: Acute Respiratory Distress Syndrome, ATS: American Thoracic Society, BALF: Bronchial-alveolar lavage fluid, CAT: Catalase, FLM: Fetal lung maturation, MAP: Mean arterial pressure, MDA: Malondialdehyde, PLs: Phospholipids, RDS: Respiratory distress syndrome, ROS: Reactive oxygen species, rpm: Revolution per minute, SOD: Superoxide dismutase, WBC: White blood cells

Acknowledgements

None.

Author Contributions

MHB conceived the idea, interpreted the results, and correction of the manuscript. SB,SB and SZG have done the experimental work, performed the analysis, and draft the first bversion of the manuscript. All authors read and approved the final manuscript.

Funding

This work was financially supported by Artajan Pharmed Company

Data Availability

The data are available by corresponding author in requast.

Declarations The authors declare that in this work, there is conflict of interest.

Ethical Approval

The proposal of the study was scientifically approved by Research Council of Mashhad University of Medical Sciences (Code: 991903), Mashhad, Iran.

Consent for Publication

Not applicable.

Ballard-Croft Cet al (2012)Large-animal models of acute respiratory distress syndrome.Ann. Thorac. Surg93(4):1331-9. https://doi.org/10.1016/j.athoracsur.2011.06.107
Ashbaugh Det al (1967)Acute respiratory distress in adults.Lancet290(7511):319-23. https://doi.org/10.1016/S0140-6736(67)90168-7
Phua Jet al(2009)Has mortality from acute respiratory distress syndrome decreased over time? A systematic review. Am J Respir Crit Care Med179(3):220-7. https://doi.org/10.1164/rccm.200805-722OC
Rubenfeld GDet al(2005)Incidence and outcomes of acute lung injury. N Engl J Med 353(16):1685-93. DOI:10.1056/NEJMoa050333
Network ARDS(2000)Ventilation with lowertidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med342(18):1301-8. DOI: 10.1056/NEJM200005043421801
Ware LB, Matthay MA(2000)The acute respiratory distress syndrome. N Engl J Med 342(18):1334-49. DOI: 10.1056/NEJM200005043421806
Bernard GR et al(1994)The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149(3):818-24. https://doi.org/10.1164/ajrccm.149.3.7509706
Bream-Rouwenhorst HRet al (2008)Recent developments in the management of acute respiratory distress syndrome in adults. Am J Health Syst Pharm 65(1):29-36. https://doi.org/10.2146/ajhp060530
Greene KE et al(1999)Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. AmJ RespirCritCareMed160(6):1843-50. https://doi.org/10.1164/ajrccm.160.6.9901117
Squara Pet al (1998)Hemodynamic profile in severe ARDS: results of the European Collaborative ARDS Study. Intensive Care Med 24(10):1018-28. https://doi.org/10.1007/s001340050710
Rudiger Met al (2005)Naturally derived commercial surfactants differ in composition of surfactant lipids and in surface viscosity. Am J Physiol-Lung Cell Mol Physiol288(2):L379-L83. https://doi.org/10.1152/ajplung.00176.2004
Christmann Uet al (2009)Role of lung surfactant in respiratory disease: current knowledge in large animal medicine. JVetInternMed23(2):227-42. https://doi.org/10.1111/j.1939-1676.2008.0269.x
Macklem PT, Proctor DF, Hogg JC(1970)The stability of peripheral airways. Respir physiol8(2):191-203. https://doi.org/10.1016/0034-5687(70)90015-0
Hills B, Chen Y(2000)Suppression of neural activity of bronchial irritant receptors by surface-active phospholipid in comparison with topical drugs commonly prescribed for asthma. Clin. Exp. Allergy30(9):1266-74. DOI: 10.1046/j.1365-2222.2000.00850.x
National Heart L, Network BIARDSCT(2006)Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med354(16):1671-84. DOI: 10.1056/NEJMoa051693
Taylor RW et al(2004)Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial. Jama291(13):1603-9.
Matute-Bello Get al(2011)An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. AmJ RespirCellMolBiol44(5):725-38. https://doi.org/10.1165/rcmb.2009-0210ST
Lachmann B, Robertson B, Vogel J(1980)In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesthesiol. Scand24(3):231-6. https://doi.org/10.1111/j.1399-6576.1980.tb01541.x
Lee VH(1991)Changing needs in drug delivery in the era of peptide and protein drugs. PeptProteinDrugDeliv1:1-56.
Berggren Pet al (1986)Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. Acta Anaesthesiol. Scand30(4):321-8. https://doi.org/10.1111/j.1399-6576.1986.tb02423.x
Šarkele Met al(2014)The Role of Oxidative Stress Markers in Developing of Acute Respiratory Distress Syndrome. Proc. Latv. Acad. Sci. B: Nat. Exact Appl. Sci 68: 200–206. DOI: 10.2478/prolas-2014-0024
Germann P G Häfner D (1998) A rat model of acute respiratory distress syndrome (ARDS): Part 1. Time dependency of histological and pathological changes. J Pharmacol Toxicol Methods 40(2):101-107. https://doi.org/10.1016/S1056-8719(98)00048-3
Ballard-Croft C et al (2012) Large-animal models of acute respiratory distress syndrome. Ann Thorac Surg 93(4):1331-1339. https://doi.org/10.1016/j.athoracsur.2011.06.107
van Helden HPM et al (1998) Efficacy of Curosurf in a rat model of acute respiratory distress syndrome. Eur Respir J; 12: 533–539.DOI: 10.1183/09031936.98.12030533
Saadat S et al (2019) Rosuvastatin affects tracheal responsiveness, bronchoalveolar lavage inflammatory cells, and oxidative stress markers in hyperlipidemic and asthmatic rats. Iran J Allergy Asthma Immunol 18(6):624-638. https://doi.org/10.18502/ijaai.v18i6.2175
Saadat S, Boskabady MH (2021)Anti-inflammatory and antioxidant effects of rosuvastatin on asthmatic, hyperlipidemic, and asthmatic-hyperlipidemic rat models.Inflammation 44(6):2279-2290. https://doi.org/10.1007/s10753-021-01499-8
Saadat S et al (2020)Rosuvastatin suppresses cytokine production and lung inflammation in asthmatic, hyperlipidemic and asthmatic-hyperlipidemic rat models.Cytokine 128 154993. https://doi.org/10.1016/j.cyto.2020.154993
Keyhanmanesh Ret al (2010)The effect of thymoquinone, the main constituent of Nigella sativa on tracheal responsiveness and white blood cell count in lung lavage of sensitized guinea pigs. PlantaMed76(03):218-22. DOI: 10.1055/s-0029-1186054
Park WYet al(2001)Cytokine balance in the lungs of patients with acute respiratory distress syndrome. AmJ RespirCritCareMed164(10):1896-1903.https://doi.org/10.1164/ajrccm.164.10.2104013
Greene KEet al(1999)Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. AmJRespirCritCareMed160(6):1843-1850.https://doi.org/10.1164/ajrccm.160.6.9901117
Bouhafs RK, Jarstrand C (2002) Effects of antioxidants on surfactant peroxidation by stimulated human polymorphonuclear leukocytes. Free Radic. Res 36(7):727-734. https://doi.org/10.1080/10715760290032593

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

The effect of arnafant surfactant on respiratory distress syndrome in rats

Status:

Version 1

Abstract

Figures

Introduction

Methods

Study groups

RDS induction

Measured criteria

Measurement of lung compliance

Total and differential WBC in the bronchial-alveolar lavage fluid and blood

Oxidant and antioxidant markers in the bronchial-alveolar lavage fluid and serum

Lung pathological evaluation

Statistical analysis

Results

The effect of RDS ant surfactant treatment on lung compliance

The effect of RDS ant surfactant treatment on lung inflammation

The effect of RDS ant surfactant treatment on lung oxidative stress

The effect of RDS ant surfactant treatment on lung pathological changes

The effect of RDS ant surfactant treatment on systemic inflammation and oxidative stress

Discussion

Conclusion

Abbreviations

Declarations

Acknowledgements

Author Contributions

Funding

Data Availability

Ethical Approval

Consent for Publication

References

Additional Declarations

Status:

Version 1