Daily Profiles of Fibrinogen Metabolism for 5 Days Following Hemorrhage and Lactated Ringer’s Resuscitation in Pigs

Abstract

This study's objective was to investigate the daily dynamics of fibrinogen metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. Then, a primed constant infusion of stable isotopes was performed in both groups daily for 5 days to measure changes in fibrinogen metabolism, together with changes in hemodynamics and coagulation function. Hemorrhage caused a decrease in mean arterial pressure and an increase in heart rate. Fluid resuscitation corrected these changes. Compared with baseline day 1, fibrinogen levels in H were decreased to 76% ± 6% by hemorrhage and resuscitation on day 1, increased to 217% ± 16% on day 2, and remained elevated afterward; clot strength in H was decreased by hemorrhage on day 1 and returned to baseline values on day 2 and afterward. Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in fibrinogen concentration and clot strength, followed by an increase in fibrinogen concentration and recovery of clot strength. The increase in fibrinogen appeared primarily due to a sustained increase in fibrinogen synthesis.