title: Impact of Time on Fluid Resuscitation with Hypertonic Saline (NaCl 7.5%) in Rats with LPS-Induced Acute Lung Injury.
abstract: Acute lung injury (ALI) is a common complication associated with septic shock that directly influences the prognosis of sepsis patients. Currently, one of the main supportive treatment modalities for septic shock is fluid resuscitation. The use of hypertonic saline (HS: 7.5% NaCl) for fluid resuscitation has been described as a promising therapy in experimental models of sepsis-induced ALI, but it has failed to produce similar results in clinical practice. Thus, we compared experimental timing versus clinical timing effectiveness (i.e., early vs. late fluid resuscitation) after the inflammatory scenario was established in a rat model of bacterial lipopolysaccharide-induced ALI. We found that late fluid resuscitation with hypertonic saline (NaCl 7.5%) did not reduce the mortality rates of animals compared with the mortality late associated with early treatment. Late fluid resuscitation with both hypertonic and normal saline increased pulmonary inflammation, decreased pulmonary function, and induced pulmonary injury by elevating metalloproteinase-2 and metalloproteinase-9 activity and collagen deposition in the animals, unlike early treatment. The animals with lipopolysaccharide-induced ALI that received late resuscitation with any kind of fluids demonstrated aggravated pulmonary injury and respiratory function. Moreover, we showed that the therapeutic window for a beneficial effect of fluid resuscitation with hypertonic saline is very narrow.
authors.affiliation: Emergency Medicine Department (LIM51), Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ricardo Costa
authors.initials: RC
authors.lastname: Petroni
authors.forename: Paolo Jose Cesare
authors.initials: PJ
authors.lastname: Biselli
authors.forename: Thais Martins de
authors.initials: TM
authors.lastname: Lima
authors.forename: Irineu Tadeu
authors.initials: IT
authors.lastname: Velasco
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D055371:Acute Lung Injury / Q000097:blood* / Q000139:chemically induced*; D000818:Animals; D003094:Collagen / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000737:chemistry; D005440:Fluid Therapy / Q000379:methods; D006360:Heat-Shock Proteins / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000503:physiopathology; D055370:Lung Injury / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011379:Prognosis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012151:Resuscitation / Q000379:methods*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D018805:Sepsis / Q000503:physiopathology; D012772:Shock, Septic / Q000503:physiopathology; D012965:Sodium Chloride / Q000737:chemistry; D013997:Time Factors
chemical_list: D016207:Cytokines; D004731:Endotoxins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D012462:Saline Solution, Hypertonic; D012965:Sodium Chloride; D003094:Collagen; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat