title: Effects of hemodynamic instability on brain death-induced prepreservation liver damage.
abstract: BACKGROUND
  Brain death (BD) is an important multifactorial variable contributing to donor-specific liver damage. Our study aimed at assessing the specific effects of hemodynamic instability on systemic and hepatic parameters of perfusion, bowel ischemia, and oxidative stress in a porcine model of BD.
  
  
  METHODS
  BD was induced in 16 pigs (German Landrace, 18-28 kg) in two groups (hypotension-BD [HYPO-BD], n=8; normotension-BD [NORM-BD], n=8), which were compared with control animals/living donors (n=6) for a period of 2 hr. We analyzed systemic hemodynamic parameters, bowel ischemia (intramucosal pH in the stomach and colon, plasma endotoxin levels, and endotoxin-neutralizing capacity [ENC]), and oxidative stress (total glutathione levels in erythrocytes) and compared the findings with hepatic parameters of perfusion (hepatic arterial flow, portal venous flow, and microperfusion) and liver oxidative stress (reduced glutathione and oxidized glutathione levels in the liver).
  
  
  RESULTS
  Independent of the hemodynamic stability, liver macrocirculation and microcirculation decreased (HYPO-BD, 79+/-6 to 69+/-10 mL/100 g/min; NORM-BD, 81+/-10 to 73+/-7 mL/100 g/min; P<0.05). Hepatocellular damage (aspartate aminotransferase: NORM-BD, 49+/-20 units/L; HYPO-BD, 170+/-140 units/L; P<0.01) and hepatic oxidative stress (reduced glutathione in the liver/oxidized glutathione in the liver: NORM-BD, 29.4+/-2.3 to 13.0+/-1.3; HYPO-BD, 29.4+/-2.3 to 9.05+/-0.81; P<0.001) increased in both BD groups. With dependence on systemic hemodynamic parameters, bowel ischemia increased (intramucosal pH in the colon, 7.22+/-0.01, P<0.01; ENC, 75+/-14 endotoxin-neutralizing units/mL, P<0.01; endotoxin levels, 7+/-2 to 43+/-10 pg/mL, P<0.01) in the HYPO-BD group but not in the NORM-BD group or the living donor group. Furthermore, systemic oxidative stress was increased in the HYPO-BD group only (total glutathione levels in erythrocytes, 2.65+/-0.25 to 0.15+/-0.25 mM; P<0.01).
  
  
  CONCLUSIONS
  During BD, liver-specific parameters (portal venous flow, microperfusion, aspartate aminotransferase activity, ENC, and hepatic oxidative stress) were compromised, independent of the hemodynamic status. Therefore, the systemic hemodynamic status does not reflect the functional status of the liver during BD.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany. Golling.Markus@t-online.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Golling
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
authors.forename: Kathrin
authors.initials: K
authors.lastname: Blum
authors.forename: Cosima
authors.initials: C
authors.lastname: Jahnke
authors.forename: Heidi
authors.initials: H
authors.lastname: Kellner
authors.forename: Octavian
authors.initials: O
authors.lastname: Bud
authors.forename: Bahram
authors.initials: B
authors.lastname: Hashemi
authors.forename: Raoul
authors.initials: R
authors.lastname: Breitkreutz
authors.forename: Katja
authors.initials: K
authors.lastname: Becker-Brandenburg
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Christian
authors.initials: C
authors.lastname: Herfarth
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraus
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D001926:Brain Death / Q000503:physiopathology*; D004731:Endotoxins / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007022:Hypotension / Q000209:etiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008107:Liver Diseases / Q000209:etiology*; D009926:Organ Preservation; D018384:Oxidative Stress; D013552:Swine
chemical_list: D004731:Endotoxins; D001219:Aspartate Aminotransferases; D005978:Glutathione