Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats

Abstract

Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5%) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5%) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.

ICU mortality is increased with high admission serum osmolarity in all patients other than those admitted with pulmonary diseases and hypoxia

“…There have been concerns around the association of hypernatraemia and mortality in unselected cohort of patients . However, based on our results, previous animal studies and provided that the hypernatraemia is induced safely (i.e. shift of <12 mmol in 24 h), we anticipate that there will be protective effect of hypernatraemia in patients with acute lung injury.…”

“…Similar to hyperosmolarity, induced hypernatraemia has also been shown to be protective in acute lung injury, with proposed mechanisms being a decrease in cellular infiltrate 8 and preservation of alveolar surfactant. 9 In keeping with this evidence, we observed previously that the phenomenon of increased ICU mortality with hypernatraemia in an unselected cohort of patients does not occur in patients with a pulmonary diagnoses, particularly those with PaO 2 /FiO 2 ratios <200.…”

The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1β transcription and activate the NLRP3 inflammasome

“…A role of chloride in the activation of the NLRP3 inflammasome has also been indicated from the inhibitory effect of high extracellular NaCl, and the chloride inhibitors NPPB and DIDs [23,24,44]. In addition, the use hypertonic solutions has been widely used to the treatment of acute conditions, such as ischemic stroke, and intracerebral hemorrhage [45,46], and has also shown to have beneficial effects in the treatment of patients with septic shock [47][48][49]. Contrary to this studies, Ip et al, reported high extracellular osmolarity being pro-inflammatory [38].…”

Perioperative “remote” acute lung injury: recent update

“…Hypertonic saline has shown benefits in animal studies, studies reported significantly lower lung injury and oedema associated with hypertonic saline administration, which is also associated with lower rate of mortality 166-167 . TNF-α inhibition has shown promising results in animal model of ALI, which may warrant further human studies with existing anti-TNF therapy 168-169 .…”