OBJECTIVES: Acute hemolysis is associated with organ damage, inflammation, and impaired vascular function. Stimulation of the cholecystokinin-1 receptor-dependent vagal anti-inflammatory reflex with lipid-rich enteral nutrition was demonstrated to prevent tissue damage and attenuate inflammation. This study investigates the effects of nutritional activation of the vagal anti-inflammatory reflex on organ integrity, systemic inflammation, and microcirculation during hemolysis. DESIGN: Prospective randomized controlled study. SETTING: University research unit. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Intravascular hemolysis was simulated by infusion of prelysed erythrocytes. Animals were fasted or received lipid-rich enteral nutrition. Pegylated (PEG)-CCK9A, A70104 (a cholecystokinin-1 receptor antagonist), and chlorisondamine (a nicotinic acetylcholine receptor antagonist) were applied to investigate involvement of the vagal reflex. MEASUREMENTS AND MAIN RESULTS: Nutritional intervention reduced hemolysis-related renal tubular cell damage, hepatocyte damage, ileal leakage of horseradish peroxidase, and bacterial translocation compared with food deprivation (all p < 0.05). Also circulating interleukin (IL)-6 levels were decreased by enteral nutrition (p < 0.05). Blockage of the cholecystokinin-1 receptor or the nicotinic acetylcholine receptor reversed the protective nutritional effects compared with vehicle (p < 0.05), whereas PEG-CCK9 mimicked the impact of enteral feeding in fasted animals (p < 0.05). Furthermore, nutritional intervention increased renal, hepatic, and intestinal blood flow compared with fasting (all p < 0.05), as evaluated using fluorescent microspheres. CONCLUSIONS: Nutritional activation of the vagal anti-inflammatory reflex preserves tissue integrity and attenuates systemic inflammation in a rodent model of acute hemolysis. In addition, lipid-rich nutrition improves renal, hepatic, and intestinal microcirculation. These findings implicate stimulation of the autonomic nervous system by nutritional means as a potential therapy to prevent complications of acute hemolysis. (Crit Care Med 2013; 41:e361-e367).
de Haan, J. J., Vermeulen Windsant, I. C., Lubbers, T., Hanssen, S. J., Hadfoune, M., Prinzen, F. W., Greve, J. W., & Buurman, W. A. (2013). Prevention of hemolysis-induced organ damage by nutritional activation of the vagal anti-inflammatory reflex*. Critical Care Medicine, 41(11), e361-367. https://doi.org/10.1097/CCM.0b013e31828e9262