Effect of whole body hypothermia on inflammation and surfactant function in asphyxiated neonates

Abstract

Hypothermia has become an evidence-based treatment for neonates with hypoxic-ischaemic encephalopathy (HIE) [1]. The usefulness of hypothermia is due to several mechanisms and among these the reduction in inflammation seems to play a relevant role [2,3]. When applied as whole body hypothermia (WBH), cooling may affect other organs as well. Recent data showed better respiratory outcomes and trends towards lower inflammation in WBH-treated preterm lambs [4], suggesting its possible usefulness to reduce lung injury through the modulation of the inflammatory pathway. By contrast, experiments with hibernating animals have shown that temperature induces significant adaptive changes to the surfactant composition and structure [5]. Nevertheless, no data are currently available in humans. Two case reports have recently described an infant [6] and an adult [7] with severe lung injury, whose ventilation had been facilitated by concurrent hypothermia. Since hypothermia is an accepted therapy only for HIE, we designed a preliminary translational study to investigate the effect of WBH on inflammation and surfactant status in neonates with HIE unaffected by any pulmonary injury.

Understanding the principle biophysics concepts of pulmonary surfactant in health and disease

“…SAT was developed by Ravasio et al [28] in 2008. However, changes in this protocol were proposed later to improve the assay sensitivity (lower volume and higher molar dye/surfactant ratio) and to test the human samples of different origin,29 30 converting SAT in a useful tool to design a bedside point of care method.…”

Description of an Automated Method for Urea Nitrogen Determination in Bronchoalveolar Lavage Fluid (BALF) of Neonates and Infants

“…Therefore, standard solutions (STDs) were prepared by serial dilutions of the above mentioned calibrator with physiological solution (0.9% NaCl). Concentration of STDs was chosen on the basis of the concentration range previously measured in BAL samples from both neonates and infants, [6][7][8] that is, from STD 6 to STD 1: 2.00 mg/dL, 1.20 mg/dL, 0.60 mg/dL, 0.30 mg/dL, 0.15 mg/dL, and 0.00 mg/ dL as blank. QC were prepared similarly to STDs to achieve a final concentration of 1.8 mg/dL for QC high and 0.15 mg/dL for QC low.…”

“…1 We and other authors have published some papers using urea nitrogen measurement in BALF and using the serumto-BALF urea ratio to correct the BAL dilution in neonates and infants. [4][5][6][7][8] A measurement of urea concentrations in BALF and serum was performed in duplicate by means of a colorimetric assay (urea nitrogen suitable on Olympus AU2700). 4 Although Capoluongo et al previously reported this method as a modified protocol on Olympus instrumentation, 4 no details were provided about the setup of a standardized method to assay urea in BALF.…”

Does Whole-Body Hypothermia in Neonates with Hypoxic–Ischemic Encephalopathy Affect Surfactant Disaturated-Phosphatidylcholine Kinetics?

“…Alternatively, it could be hypothyzed that the adrenergic stimuli may induce surfactant mobilization and production from type 2 pneumocytes. De Luca et al ., studied pulmonary surfactant activity by fluorescence analysis of adsorption and found a significant increase in surfactant function after 48 h of WBH in neonates with HIE and no injured lungs, suggesting that adaptive mechanisms could act in surfactant modulation [ 10 ]. More information and studies designed to measure surfactant composition and production during systemic hypothermia may help understanding the effect of this treatment in severe lung injury [ 25 , 26 ].…”

“…De Luca et al . have recently reported significant reductions in IL-6 and IL-8 levels in Epithelial Lining Fluid during WBH [ 10 ].…”