Effects of Intrauterine Growth Restriction (IUGR) on the Surfactant System in Response to Sepsis

Abstract

IntroductionAcute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction. The lung impairments in ARDS result, in part, from alterations to pulmonary surfactant; a lipid‐protein mixture coating the inside of the lung that increases the lung compliance during respiration. The most common cause of ARDS is sepsis and due to a lack of effective pharmacological therapies the mortality associated with this condition is over 30%. Our research focuses on risk factors that indicate a susceptibility to the disease, which could provide new and early therapeutic options. One such potential risk factor is intrauterine growth restriction (IUGR). IUGR is defined by a low birth weight and contributes to a variety of adult‐onset diseases with different severities between males and females. There are underlying shared mechanisms between these IUGR‐induced diseases and ARDS, such as systemic inflammation. This study investigates the IUGR effect on surfactant system in response to sepsis in adult males and females. It was hypothesized that IUGR is a risk factor for developing ARDS through surfactant alterations with different outcomes between adult males and females.MethodsIUGR was induced in pregnant rat model via a low protein diet. At postnatal day 130, control and IUGR rats were randomly assigned into sham and septic groups. Rats were anesthetized and received either an intraperitoneal injection (IP) of saline or fecal slurry solution (1m/100g at 0.5g/ml). Following injection, respiratory rate and the animal activity were monitored for 6hr. After 6hr, animals were sacrificed (sodium pentobarbital IP injection) and arterial blood and the surfactant were taken for cytokine and surfactant analysis. Some non‐lavaged lungs were fixed for histological assessments.ResultsIUGR was confirmed by significant decrease in birth weight in both male and female offspring. Septicemia was confirmed by culturing bacteria from the blood samples, while cultures from sham animals were negative. After 6hr, respiratory rates significantly decreased in septic male and female IUGRs compare to sham male and female IUGRs at time zero (before IP) (p<0.01). Surfactant analysis showed significant reduction in the total surfactant phospholipid content in septic male IUGRs compared to shams (p<0.05) with no changes in surfactant phospholipid content between female septic IUGRs and shams. Control groups demonstrated no changes in surfactant content between septics and shams in either sexes.DiscussionChanges in surfactant pools occurring between male IUGR septic animals compared to shams without changes in control animals, support our hypothesis that IUGR is a risk factor for developing surfactant impairments. Also, the results indicate that the effect is different between males and females. Reduction of surfactant content in septic IUGR males could potentially cause lower lung compliance, alter lung function and therefore, developing or exacerbating lung injury during the development of ARDS. To further study the IUGR effect on the surfactant and evaluate its role as an ARDS risk factor, future experiments will assess the surfactant biophysical properties and lung histology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.