title: Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.
abstract: BACKGROUND
  Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome.
  
  
  METHODS
  30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels.
  
  
  RESULTS
  TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb.
  
  
  CONCLUSIONS
  Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. jesper.sperber@dll.se.|Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden. jesper.sperber@dll.se.|Department of Anaesthesiology and Intensive Care, Mälarsjukhuset Eskilstuna, Sweden. jesper.sperber@dll.se.
authors.forename: Jesper
authors.initials: J
authors.lastname: Sperber
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden. miklos.lipcsey@sugsci.uu.se.
authors.forename: Miklós
authors.initials: M
authors.lastname: Lipcsey
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden. anders.larsson@surgsci.uu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Biochemical structure and function, Uppsala University, Uppsala, Sweden. anders.larsson@akademiska.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden. jan.sjolin@akademiska.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
authors.affiliation: Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden. markus.castegren@gmail.com.|Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden. markus.castegren@gmail.com.|Department of Anaesthesiology and Intensive Care, Mälarsjukhuset Eskilstuna, Sweden. markus.castegren@gmail.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Castegren
mesh_terms: D000818:Animals; D002339:Carotid Arteries; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D006503:Hepatic Veins; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007601:Jugular Veins; D008297:Male; D011169:Portal Vein; D011175:Positive-Pressure Respiration; D011183:Postoperative Complications / Q000276:immunology*; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods*; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology*; D013552:Swine; D013990:Tidal Volume; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control
chemical_list: D016207:Cytokines; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10