Effects of hemodynamic instability on brain death-induced prepreservation liver damage.

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.