Increased hepatic blood flow during enteral immune-enhancing diet gavage requires intact enterohepatic bile cycling.

OBJECTIVES: Total hepatic blood flow (HBF) via the hepatic artery and portal vein is highly dependent on gastrointestinal perfusion. During postprandial hyperemia, intestinal blood flow depends on nutrient composition, gastrointestinal location, and time. Immune-enhancing diets (IEDs) containing n-3 polyunsaturated fatty acids (PUFAs) selectively augment blood flow in the ileum at 60-120 min via a bile-dependent mechanism. My colleagues and I hypothesized that liver blood flow would be similarly affected by IEDs containing n-3 PUFAs. METHODS: Mean arterial blood pressure, heart rate, and effective HBF (galactose clearance) were measured in anesthetized male Sprague-Dawley rats after gastric gavage of either a control diet (CD, Boost, Novartis) or an IED (Impact, Nestle Nutrition), with or without bile-duct ligation (BDL), and with or without supplemental bile (bovine, dried, unfractionated). Significance was assessed by 2-way ANOVA for repeated measures with the Tukey-Kramer honestly significant difference test. RESULTS: Compared with baseline levels, a CD increased HBF (peak at 40 min , *P < 0.05) whereas an IED increased HBF in two distinct peaks at 40 min (*P < 0.05) and 120 min (*P < 0.05), but BDL prevented both the early (CD and IED, †P < 0.05) and late peaks (IED, †P < 0.05). Bile supplementation in the CD + BDL or IED + BDL groups restored neither the CD peak nor the early or late IED peaks. CONCLUSIONS: HBF during absorptive intestinal hyperemia is modulated by a mechanism that requires an intact enterohepatic circulation. The early peaks at 40 min (CD or IED) were prevented by BDL, even though fat absorption in the proximal gut occurs by bile-independent direct absorption. Bile supplementation with the diet (CD + BDL or IED + BDL) was insufficient to restore HBF hyperemia, which implies that a relationship exists between intestinal and hepatic blood flow that is not solely dependent on bile-mediated intestinal fat absorption and bile recirculation.

Fish oil increases blood flow in the ileum during chronic feeding in rats.

Benefits of enteral feeding with immune-enhancing diets (IEDs) depend on route, timing, and composition. We hypothesized that chronic enteral feeding with certain individual immunonutrients would enhance gastrointestinal blood flow. Male rats were fed a standard enteral diet supplemented with immunonutrients for 5 days before study. Groups were (1) standard rat chow, (2) liquid control diet (CD) alone (CD), (3) CD + fish oil, (4) CD + L-arginine, and (5) CD + RNA fragments. Whole organ blood flow distribution was measured by colorimetric microsphere technique in antrum, small intestine (in thirds), colon, liver, spleen, pancreas, and kidneys. Chronic feeding for 5 days with CD + fish oil increased blood flow in the distal third of the small intestine compared with CD alone, whereas feeding with CD + L-arginine decreased blood flow in the small intestine (all segments) compared with CD alone. Acute gavage of CD + L-arginine or CD + fish oil increased blood flow in the proximal and middle third of the small intestine compared with CD alone. Control diet + RNA increased blood flow in the proximal small intestine compared with CD alone. These findings support prior acute feeding studies with CD, CD + individual immunonutrients, or IED. Our current data suggest that blood flow benefits associated with fish oil persist during chronic feeding in rats. Enhanced gastrointestinal perfusion might partially explain the benefits of early enteral feeding with IEDs not seen with regular enteral diets and parenteral immunonutrient delivery.

Enteral glutamine supplementation impairs intestinal blood flow in rats.

BACKGROUND: Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow. METHODS: Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine. RESULTS: There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow. CONCLUSIONS: Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow-transplant patients).

Immune-enhancing enteral diet selectively augments ileal blood flow in the rat.

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 diets). Gut exposure to an IED seems to preserve and/or augment intestinal mucosal immunity. However, nutrient absorption stimulates gut blood flow in a nutrient-specific manner (i.e., postprandial hyperemia). 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 lymphoid tissue (GALT) or mucosa-associated lymphoid tissue (MALT). METHODS: Male Sprague-Dawley rats (200-225 g) were anesthetized and cannulated for colorimetric microsphere 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 integrity of the microsphere technique and assay. Control diet augmented blood flow compared to IED in the antrum, duodenum, jejunum, and spleen. Conversely, IED gavage stimulated a delayed and sustained hyperemic 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 distribution 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 perfusion of the terminal ileum during IED nutrient absorption.