title: Resuscitation fluid composition affects hepatic inflammation in a murine model of early sepsis.
abstract: BACKGROUND
  Fluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. We have previously demonstrated that resuscitation with normal saline results in increased hepatic leukocyte recruitment in a murine model of sepsis. Given that clinical formulations of albumin are in saline, our objectives were to develop a novel balanced electrolyte solution specifically for sepsis and to determine if supplementing this solution with albumin would improve the inflammatory response in sepsis.
  
  
  METHODS
  We developed two novel buffered electrolyte solutions that contain different concentrations of acetate and gluconate, named Seplyte L and Seplyte H, and administered these solutions with or without 5% albumin. Normal saline with or without albumin and Ringer's lactate served as controls. Sepsis was induced by cecal ligation and puncture (CLP), and the liver microvasculature was imaged in vivo at 6 h after CLP to quantify leukocyte recruitment. Hepatic cytokine expression and plasma cell-free DNA (cfDNA) concentrations were also measured.
  
  
  RESULTS
  Septic mice receiving either Seplyte fluid showed significant reductions in hepatic post-sinusoidal leukocyte rolling and adhesion compared to normal saline. Hepatic cytokine concentrations varied in response to different concentrations of acetate and gluconate in the novel resuscitation fluids but were unaffected by albumin. All Seplyte fluids significantly increased hepatic TNF-α levels at 6 h compared to control fluids. However, Seplyte H exhibited a similar cytokine profile to the control fluids for all other cytokines, whereas mice given Seplyte L had significantly elevated IL-6, IL-10, KC (CXCL1), and MCP-1 (CCL2). Plasma cfDNA was generally increased during sepsis, but resuscitation fluid composition did not significantly affect cfDNA concentrations.
  
  
  CONCLUSIONS
  Electrolyte concentrations and buffer constituents of resuscitation fluids can modulate hepatic cytokine production and leukocyte recruitment in septic mice, while the effects of albumin are modest during early sepsis. Therefore, crystalloid fluid choice should be an important consideration for resuscitation in sepsis, and the effects of fluid composition on inflammation in other organ systems should be studied to better understand the physiological impact of this vital sepsis therapy.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Patrick
authors.affiliation: Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada.|Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton St. East, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Grin
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kraus
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Gold
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Berardocco
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton St. East, Hamilton, ON, L8L 2X2, Canada.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Liaw
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. afoxrob@mcmaster.ca.|Thrombosis and Atherosclerosis Research Institute, McMaster University, DBRI C5-106, 237 Barton St. East, Hamilton, ON, L8L 2X2, Canada. afoxrob@mcmaster.ca.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Fox-Robichaud
keywords: Albumin; Cecal ligation and puncture; Cell-free DNA; Chemokine; Cytokine; Intravital microscopy; Leukocyte recruitment; Resuscitation fluid; Sepsis