Differential Changes in Hepatic Synthesis of Albumin and Fibrinogen After Severe Hemorrhagic Shock in Pigs

Abstract

Changes of plasma albumin and fibrinogen after various insults have been described as acute phase responses. This study investigated the acute changes of hepatic synthesis of albumin and fibrinogen after hemorrhage and resuscitation with lactated Ringer's (LR) solution or normal saline (NS) in pigs. Twenty anesthetized pigs were randomized into control (n = 6), LR solution (n = 7), and NS (n = 7) groups. Hemorrhage of 60% estimated blood volume was induced in the LR and NS groups by removing blood from the left femoral artery with a computer-controlled pump, followed by resuscitation with either LR solution at three times the bled volume, or NS to reach the same mean arterial pressure as in the LR group. Stable isotope 1-C-phenylalanine was infused for 6 h with hourly blood sampling and subsequent gas chromatography and mass spectrometry analysis to quantify hepatic protein synthesis. Hemorrhage decreased mean arterial pressure and increased heart rate. Resuscitation with LR solution or NS corrected these changes. Compared with baseline, hemorrhage and resuscitation decreased albumin levels to 49% ± 2% and 44% ± 3% and fibrinogen levels to 50% ± 2% and 53% ± 2% in LR solution and NS (all P < 0.05), respectively. Albumin synthesis was impaired from 8.8 ± 1.4 mg/kg per hour (control) to 5.3 ± 0.8 mg/kg per hour in LR solution and 3.9 ± 0.6 mg/kg per hour in NS (both P < 0.05). No changes were observed in fibrinogen synthesis after hemorrhage and resuscitation with LR solution (4.4 ± 0.7 mg/kg per hour) or NS (3.3 ± 0.4 mg/kg per hour), compared with the control (3.5 ± 0.3mg/kg per hour). Hemorrhage and resuscitation compromised albumin synthesis, but not fibrinogen synthesis. There were no differences in hepatic synthesis of albumin or fibrinogen between LR solution and NS resuscitation.