Parasympathetic Stimulation Via the Vagus Nerve Prevents Systemic Organ Dysfunction by Abrogating Gut Injury and Lymph Toxicity in Trauma and Hemorrhagic Shock

Abstract

To the Editor We would like to congratulate Dr. Levy and all coauthors on their experimental study showing that vagus nerve stimulation (VNS) abrogated gut injury and lymph toxicity in trauma and hemorrhagic shock (1). This interesting and important study shows that mechanical VNS reduced gut injury upon combined trauma and hemorrhagic shock. Although VNS resulted in significant protective effects, the authors mention that the clinical use of VNS is limited and therefore strive toward a pharmacological intervention. It was previously shown that apart from mechanical or pharmaceutical stimulation, the autonomic nervous system can also be stimulated in a physiological way via dietary fat (2). Ingestion of dietary lipids, proteins, and peptides triggers release of cholecystokinin that predominantly binds to cholecystokinin 1 receptors located on afferent vagal fibers (3). In this way, the autonomic nervous system is rapidly activated via vagal afferents resulting in a reduction of the inflammatory response by binding of acetylcholine to α7 nicotinic receptors on inflammatory cells (2). Furthermore, nutritional stimulation of the vagus nerve preserves intestinal barrier function at an early stage. Reduction of mast cell activation and reduction of neutrophil influx (4) are involved in this process. This protection of intestinal barrier function by lipid-enriched enteral nutrition results in reduced bacterial translocation to mesenteric lymph nodes and distant organs and reduced circulating endotoxin levels following hemorrhagic shock (5). Besides hemorrhagic shock, the protective effects of this nutritional intervention with dietary fat have been proven to be very efficient in various other experimental models including a two-hit model of hemorrhagic shock and bacterial infection and a model of bowel manipulation (6, 7). Recently, we expanded the experimental animal data in a human preclinical study showing that continuous administration of enriched enteral nutrition resulted in a rapid anti-inflammatory effect in a human model of endotoxemia (8). Timing of the intervention is essential, and VNS is most effective when given just before the inciting event, as was done in the article of Levy et al. However, our group has also shown that nutritional stimulation of the vagus nerve via dietary lipids preserves intestinal barrier integrity when given after the hemorrhagic shock (9). Stimulation of the vagus nerve following events such as severe trauma may therefore be a potential therapy to attenuate gut injury and its sequelae. Besides mechanical and pharmacological activation of the vagus nerve, nutritional stimulation is a simple and physiological way to achieve this stimulation also in a clinical setting. Misha D. Luyer Department of Surgery Catharina Hospital Eindhoven The Netherlands Jacco-Juri de Haan Department of Internal Medicine Medisch Spectrum Twente Enschede, The Netherlands Tim Lubbers Department of Surgery Maastricht University Medical Centre The Netherlands Jan Willen M. Greve Department of Surgery Atrium Medisch Centrum Heerlen, The Netherlands Wim A. Buurman Institute Nutrim Maastricht University The Netherlands