title: Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.
abstract: Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS.
  
  
  
  Twenty-four Wistar rats were randomized to undergo general anesthesia (1-2 minutes) with sevoflurane and isoflurane. Animals were then further randomized to receive Escherichia coli lipopolysaccharide (LPS) intratracheally (ARDSp) or intraperitoneally (ARDSexp), and 24 hours after ARDS induction, they were subjected to 60 minutes of sevoflurane or isoflurane anesthesia at 1 minimal alveolar concentration. The primary outcome measure was interleukin (IL)-6 mRNA expression in lung tissue. Secondary outcomes included gas exchange, lung mechanics, histology, and mRNA expression of IL-10, nuclear factor erythroid 2-related factor-2 (Nrf2), surfactant protein (SP)-B, vascular cell adhesion molecule-1, epithelial amiloride-sensitive Na-channel subunits α and γ, and sodium-potassium-adenosine-triphosphatase pump subunits α1 (α1-Na,K-ATPase) and β1 (β1-Na,K-ATPase). Additional ARDSp and ARDSexp animals (n = 6 per group) were anesthetized with sodium thiopental but not mechanically ventilated (NV) to serve as controls. Separately, to identify how sevoflurane and isoflurane act on type II epithelial cells, A549 human lung epithelial cells were stimulated with LPS (20 µg/mL) for 24 hours, and SP-B expression was quantified after further exposure to sevoflurane or isoflurane (1 minimal alveolar concentration ) for 60 minutes.
  
  
  
  In ARDSp, sevoflurane reduced IL-6 expression to a greater degree than isoflurane (P = .04). Static lung elastance (P = .0049) and alveolar collapse (P = .033) were lower in sevoflurane than isoflurane, whereas Nrf2 (P = .036), SP-B (P = .042), and β1-Na,K-ATPase (P = .038) expressions were higher in sevoflurane. In ARDSexp, no significant differences were observed in lung mechanics, alveolar collapse, or molecular parameters between sevoflurane and isoflurane. In vitro, SP-B expression was higher in sevoflurane than isoflurane (P = .026).
  
  
  
  Compared with isoflurane, sevoflurane did not affect lung inflammation in ARDSexp, but it did reduce lung inflammation in ARDSp.
authors.affiliation: From the *Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute; †Department of Surgical Sciences and Integrated Diagnostics; ‡Center of Experimental Surgery, Department of Surgery, School of Medicine; §Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; ‖Department of Surgical Sciences and Integrated Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria, San Martino-IST, University of Genoa, Genoa, Italy; ¶Division of Anesthesiology, Department of Surgery, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Araújo
authors.forename: Cíntia L
authors.initials: CL
authors.lastname: Santos
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Samary
authors.forename: Luciana B B
authors.initials: LBB
authors.lastname: Heil
authors.forename: Vinicius C M
authors.initials: VCM
authors.lastname: Cavalcanti
authors.forename: Fernanda F
authors.initials: FF
authors.lastname: Cruz
authors.forename: Nathane S
authors.initials: NS
authors.lastname: Felix
authors.forename: Johnatas D
authors.initials: JD
authors.lastname: Silva
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.forename: Fatima C
authors.initials: FC
authors.lastname: Fernandes
authors.forename: Nivaldo R
authors.initials: NR
authors.lastname: Villela
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
authors.forename: Patricia R M
authors.initials: PRM
authors.lastname: Rocco
mesh_terms: D000072283:A549 Cells; D000777:Anesthetics; D000818:Animals; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007530:Isoflurane / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000187:drug effects*; D008738:Methyl Ethers / Q000627:therapeutic use*; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology; D000077149:Sevoflurane; D013997:Time Factors
chemical_list: D000777:Anesthetics; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane