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Nutritional activation of the cholinergic pathway after hemorrhagic shock reduces inflammation and preserves intestinal integrity

Introduction

This study investigates the effects of lipid-enriched nutrition administered early after hemorrhagic shock. Previously we have shown that high-lipid feeding effectively inhibits systemic inflammation and preserves intestinal integrity when given before hemorrhagic shock by stimulation of the cholinergic anti-inflammatory pathway via activation of CCK receptors. Control of the inflammatory status of trauma patients forms a major clinical problem since the inflammatory cascade is already ongoing upon presentation. The anti-inflammatory effects of high-lipid intervention after shock are therefore examined.

Methods

Hemorrhagic shock in rats was induced by extracting 30–40% of the circulating volume. Animals were subsequently fasted or given enteral feedings containing high or low concentrations of lipids at 30 and 180 minutes after shock (n = 8). CCK-receptor antagonists were administered 10 minutes before feeding. Tissue and plasma were collected 4 hours after shock to assess inflammation and intestinal integrity.

Results

Administration of lipid-enriched nutrition early after shock significantly reduced plasma levels of IFNγ at 4 hours (0.39 ± 0.06 ng/ml) compared with low-lipid treated (0.77 ± 0.09; P < 0.01) and fasted animals (1.38 ± 0.11; P < 0.001). Enterocyte damage, expressed as circulating levels of ileal lipid binding protein, was prevented by high-lipid feeding compared with animals that received a low-lipid composition or were fasted (3.7 ± 0.3 vs 4.9 ± 0.5 vs 8.0 ± 1.1 pg/ml; P < 0.05 respective P < 0.0001). Furthermore, early post-shock intervention with lipid-enriched feeding significantly reduced translocation of bacteria to distant organs (69.7 ± 6.4 vs low lipid: 100.9 ± 9.2 CFU/g tissue; P < 0.05). Blockage of CCK receptors abrogated the anti-inflammatory effects of high-lipid nutrition (IFNγ 1.18 ± 0.15 vs vehicle 0.58 ± 0.14 ng/ml; P < 0.05).

Conclusion

Administration of lipid-enriched nutrition after hemorrhagic shock reduces inflammation and preserves intestinal integrity. This study implicates lipid-enriched nutrition as a potential therapeutic option in settings in which inflammation and tissue damage are already present, such as in trauma patients.

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De Haan, J., Lubbers, T., Hadfoune, M. et al. Nutritional activation of the cholinergic pathway after hemorrhagic shock reduces inflammation and preserves intestinal integrity. Crit Care 12, P143 (2008). https://doi.org/10.1186/cc6364

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Keywords

  • Ileal
  • Trauma Patient
  • Hemorrhagic Shock
  • Enteral Feeding
  • Lipid Binding