Enteral administration of high-fat nutrition before and directly after hemorrhagic shock reduces endotoxemia and bacterial translocation

Abstract

Objective: To determine whether potential enhancement of endotoxin neutralization via high-fat enteral nutrition affects endotoxemia and bacterial translocation after hemorrhage.

Summary background data: Endotoxin and bacterial translocation due to gut barrier failure are important initiating events in the pathogenesis of sepsis after hemorrhage. Systemic inhibition of endotoxin activity attenuates bacterial translocation and distant organ damage. Triacylglycerol-rich lipoproteins constitute a physiological means of binding and neutralizing endotoxin effectively. We hypothesized that enhancement of triacylglycerol-rich lipoproteins via high-fat enteral nutrition would reduce endotoxemia and prevent bacterial translocation.

Methods: A rat model of nonlethal hemorrhagic shock was used. Hemorrhagic shock (HS) rats were divided into 3 groups: rats starved overnight (HS-S); rats fed with a low-fat enteral diet (HS-LF), and rats receiving a high-fat enteral diet (HS-HF).

Results: Circulating triacylglycerol and apolipoprotein B, reflecting the amount of triacylglycerol-rich lipoproteins, were elevated in HS-HF rats compared with both HS-S rats (P <or= 0.005 and P <or= 0.05, respectively) and HS-LF rats (P <or= 0.005 and P <or= 0.05). Circulating endotoxin was lower in HS-HF rats (7.2 +/- 10.2 pg/ml) compared with both HS-S rats (29.1 +/- 13.4 pg/ml, P <or= 0.005) and HS-LF rats (29.9 +/- 5.2 pg/ml, P <or= 0.005). In line, bacterial translocation was lower in HS-HF rats (incidence 4/8 rats; median 3 [range 0-144] cfu/g) compared with both HS-S rats (8/8; 212 [60-483] cfu/g; P = 0.006), and HS-LF rats (8/8; 86 [30-209] cfu/g; P = 0.002).

Conclusion: This study is the first to show that high-fat enteral nutrition, leading to increased plasma triacylglycerol and apolipoprotein B levels, significantly decreases endotoxemia and bacterial translocation after hemorrhage.

Figures

FIGURE 1. Experimental procedure and feeding schedule. At -18 hours, rats were starved overnight (1), 45 minutes before withdrawal of blood anesthesia was given and a femoral artery catheter inserted (2); at t = 0, hemorrhagic shock was induced (3); after 50 minutes, the femoral artery catheter was removed and the wound was closed (4); after 6 hours, all shock groups were allowed standard chow ad libitum (5); at 24 hours after (sham) shock (t = 24 hours), rats were killed (6). A liquid enteral nutrition (low-fat or high-fat) was administered via gavage in the fed groups (HS-LF and HS-HF), at −18 hours (3 mL), −2 hours (0.75 mL), −45 minutes (0.75 mL), +3 hoursv(0.75 mL), and +6 hours (0.75 mL).

FIGURE 2. Mean arterial pressure (MAP) of shock rats during the observation period. MAP pressure is represented as median with 25th–75th percentile. MAP pressure before shock (pre) was 100 (90–110) mmHg and decreased to 26 (23–31) mmHg directly after hemorrhage (t = 0). There was no significant difference in MAP between the groups during the observation period.

FIGURE 3. High-fat enteral nutrition leads to enhanced triglyceride and apoB concentrations. (A) Triglyceride concentrations in plasma were significantly increased in HS-HF rats at both t = 0 (diagonally striped bars) and 24 hours later (horizontally striped bars) compared with both HS-S and HS-LF groups. Values are expressed as mean ± SD. *P < 0.005 versus HS-S group at t = 0. **P < 0.001 versus HS-S group at t = 24 hours. †P < 0.005 versus HS-LF group at t = 0. ‡P < 0.001 versus HS-LF group at t = 24 hours. (B) ApoB in the HS-HF group at t = 0 was significantly higher compared with the HS-LF group, *P = 0.006. At t = 24 hours, apoB concentrations in the HS-HF group were significantly higher compared with the HS-S group, †P = 0.036. Values are expressed as percentage of the apoB concentration in pooled plasma of healthy rats. Concentration of apoB in Control, Sham-Shock, fasted Hemorrhagic Shock (HS) groups, and the HS group fed with a low-fat enteral diet did not significantly differ.

FIGURE 4. Circulating endotoxin at 24 hours after shock. Circulating endotoxin is significantly lower in the HS-HF group compared with both the HS-S group (*P = 0.005) and the HS-LF group (†P = 0.002). Each individual measurement is presented with the 5th and 95th percentile and mean ± SD.

FIGURE 5. Circulating triglycerides are inversely correlated with total bacterial translocation and circulating endotoxin in all hemorrhagic shock rats. (A) Circulating triglycerides are inversely correlated with total bacterial translocation. Total bacterial translocation expressed as colony forming units (cfu) per gram (g) is plotted against circulating triglycerides (mg/dL), r = −0.346, *P ≤ 0.05. (B) Circulating triglycerides are inversely correlated with the circulating endotoxin level at t = 24 hours. Circulating endotoxin (pg/ml) is plotted against circulating triglycerides (mg/dL), r = -0.598, **P −0.01.