Immune-Enhancing Enteral Diet Selectively Augments Ileal Blood Flow in the Rat 1 Diane Rhoden, M.D.,* Paul J. Matheson, Ph.D.,† Nicholas D. Carricato, M.S.,† David A. Spain, M.D.,* , ‡ and R. Neal Garrison, M.D.* , † , ‡ *Department of Surgery and †Department of Physiology & Biophysics, University of Louisville, Louisville, Kentucky 40292; and ‡Louisville Veterans Affairs Medical Center, Louisville, Kentucky 40206 Submitted for publication June 26, 2001; published online June 28, 2002 Background. Clinical studies show that immune- enhancing enteral diets (IED; with L-arginine, fish oil, and RNA fragments) decrease the rate of sepsis and shorten the length of hospital stay after the start of enteral feeding. These beneficial effects are dependent on the route of administration (enteral vs parenteral) and on the nutrient composition (IED vs standard di- ets). Gut exposure to an IED seems to preserve and/or augment intestinal mucosal immunity. However, nu- trient absorption stimulates gut blood flow in a nutrient-specific manner (i.e., postprandial hyper- emia). We hypothesized that an IED would initiate a different pattern of whole organ blood flow compared to a standard diet. This suggests that a mechanism for the protective effect of IED might be the preferential augmentation of gut blood flow to gut-associated lym- phoid tissue (GALT) or mucosa-associated lymphoid tissue (MALT). Methods. Male Sprague–Dawley rats (200 –225 g) were anesthetized and cannulated for colorimetric mi- crosphere determination of blood flow distribution (with the phantom organ technique). Animals received gastric gavage (2 ml) of an IED (Impact; Novartis) or an isocaloric, isonitrogenous control diet (Boost; Mead–Johnson). Blood flow to the antrum, duodenum, jejunum, ileum, colon, liver, kidneys, and spleen was determined at baseline and 30, 60, 90, and 120 min after gavage. Results. Baseline blood flows to the left and right kidneys were within 10%, indicating the technical in- tegrity of the microsphere technique and assay. Con- trol diet augmented blood flow compared to IED in the antrum, duodenum, jejunum, and spleen. Conversely, IED gavage stimulated a delayed and sustained hyper- emic response in the ileum. IED also increased hepatic blood flow early (30 min). IED increased blood glucose levels compared to control diet at 30, 60, and 90 min, suggesting enhanced nutrient absorption. Conclusions. These data show that blood flow distri- bution depends on nutrient composition and that IED preferentially augments blood flow to the ileum. Since the terminal jejunum and ileum contain much of the GALT, our data suggest that a mechanism for enterally stimulated mucosal immunity involves selective per- fusion of the terminal ileum during IED nutrient absorption. © 2002 Elsevier Science (USA) Key Words: postprandial; hyperemia; intestine; blood flow; colorimetric microspheres; phantom organ; Im- pact; Boost. INTRODUCTION A major cause of late death from trauma and burns is sepsis and septic-related complications [1, 2]. Re- cently much attention has been given to the role nutri- tion might play in combating these complications such as at the U.S. Summit on Immune-Enhancing Enteral Therapy recently held in San Diego [3]. Studies have examined the route (parenteral vs enteral) [4], timing (early vs delayed) [5, 6], and composition of nutrition and the roles they may play in minimizing septic deaths and complications [7]. Several studies have ex- amined the role of “immune-enhancing enteral nutri- tion” with supplemental arginine, glutamine, -3 fatty acids, and nucleotides in enhancing immune function and thereby outcomes for patients at high risk of com- plications and death from sepsis [7]. In general the results of these studies overwhelmingly suggest im- proved immunocompetence from “immune-enhancing” 1 This work was supported in part by VA Merit Review funding (R.N.G.). Presented at the 25th Annual Surgical Symposium of the Associ- ation of Veterans Administration Surgeons, Atlanta, Georgia, May 6 – 8, 2001. Journal of Surgical Research 106, 25–30 (2002) doi:10.1006/jsre.2002.6424 25 0022-4804/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.