Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory response characterized by damage of the vesicular-capillary membrane . ARDS was first described in humans about 50 years ago during the Vietnam War as "shock lung" or "DaNang lung" , 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 . 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 .
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 .
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 , 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 . The potential role of surfactant in the preservation of terminal bronchi was first described in 1970 by McLem et al., . Surfactant is a protective barrier against surface tension and invasion of microorganisms into the lungs .
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 . 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 .
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 . 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 . 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 .
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.