Maintaining Gut Function Research Articles

Amino acid solution mitigates hypothermia response and intestinal damage following exertional heat stroke in male mice.

Increased gut permeability is implicated in the initiation and extent of the cytokine inflammatory response associated with exertional heat stroke (EHS). The primary objective of this study was to determine if a five amino acid oral rehydration solution (5AAS), specifically designed for the protection of the gastrointestinal lining, would prolong time to EHS, maintain gut function and dampen the systemic inflammatory response (SIR) measured during EHS recovery. Male C57/BL6J mice instrumented with radiotelemetry were gavaged with 150 μL of 5AAS or H2 O, and ≈12 h later were either exposed to an EHS protocol where mice exercised in a 37.5°C environmental chamber to a self-limiting maximum core temperature (Tc,max) or performed the exercise control (EXC) protocol (25°C). 5AAS pretreatment attenuated hypothermia depth and length (p < 0.005), which are indicators of EHS severity during recovery, without any effect on physical performance or thermoregulatory responses in the heat as determined by percent body weight lost (≈9%), max speed (≈6 m/min), distance (≈700 m), time to Tc,max (≈160 min), thermal area (≈550°C∙min), and Tc,max (42.2°C). EHS groups treated with 5AAS showed a significant decrease in gut transepithelial conductance, decreased paracellular permeability, increased villus height, increased electrolyte absorption and changes in tight junction protein expression pattern suggestive of improved barrier integrity (p < 0.05). No differences were witnessed between EHS groups in acute phase response markers of liver, circulating SIR markers, or indicators of organ damage during recovery. These results suggest that a 5AAS improves Tc regulation during EHS recovery through maintaining mucosal function and integrity.

Inhibition of jejunal protein synthesis and breakdown in Pseudomonas aeruginosa-induced sepsis pig model.

Maintenance of gut integrity has long been recognized as crucial for survival in sepsis, but alterations in protein metabolism have not previously been documented. Therefore, in the present study, we measured in a Pseudomonas aeruginosa-induced porcine sepsis model fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted, conscious state. FSR was measured by the incorporation rate of stable tracer amino acid (l-[ring-13C6]phenylalanine) into tissue protein. FBR was determined using the relation between blood arterial enrichment and intracellular enrichment of phenylalanine in consecutive mucosal biopsies after a pulse of l-[15N]phenylalanine. Additionally, we determined the FSR in jejunum, ileum, liver, muscle, and lung tissue. We found in this sham-controlled acute sepsis pig model (control: n = 9; sepsis: n = 13) that jejunal mucosal protein turnover is reduced with both decreased FSR (control: 3.29 ± 0.22; sepsis: 2.32 ± 0.12%/h, P = 0.0008) and FBR (control: 0.72 ± 0.12; sepsis: 0.34 ± 0.04%/h, P = 0.006). We also found that FSR was unchanged in ileum and muscle, whereas it was higher in the liver (control: 0.87 ± 0.05; sepsis: 1.05 ± 0.06%/h, P = 0.041). Our data, obtained with a translational acute sepsis model, suggest that jejunal mucosal protein metabolism is diminished in acute sepsis. Comparison with other tissues indicates that the most serious acute metabolic changes in sepsis occur in the jejunum rather than the muscle. NEW & NOTEWORTHY In a highly translational acute sepsis model, presented data suggest that jejunal mucosal protein metabolism is diminished in acute sepsis, even if the origin of the sepsis is not located in the gut. Comparison with other tissues indicates that the most serious acute changes in the protein synthesis rates in sepsis occur in the gut rather than the muscle. Therefore, we hypothesize that preventing a compromised gut is critical to maintain gut function during sepsis.

Gastrointestinale Motilitätsstörungen auf der Intensivstation – Ursachen, Konsequenzen und Therapie

Maintaining regular function of the intestinal tract is an important prerequisite for successful outcomes in critical illness. Disturbances of gastrointestinal motility are frequently caused by drugs, excessive fluid load, mechanical ventilation, surgical or ischemic damage, and occur frequently in sepsis and SIRS. Impaired gastrointestinal motility may give rise to a vitious circle of enteral nutrition intolerance, edema, and may eventually result in a breakdown of the gastrointestinal barrier. Early diagnosis, patient-adapted treatment and a focus on prophylactic measures are necessary prerequisites to maintain gut function in critically ill patients.

W1933 Expression of PYY is Unchanged in Rat Small Intestine During a High-Fat Diet

Purpose: Aging is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during aging. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of aging. Methods: Female young mice (2-5 month; n=6), aged mice (~21 months; n=6) and aged mice treated with melatonin (~21 months; n=6; 10mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin (MEL) concentrations near the mucosal surface of ileum and distal colon. Amperometry was used to record compression evoked 5-HT while cyclic voltammetry was used to identify peaks for 5-HT and MEL. Differential pulse voltammetry (DPV: 500/800mV) was used to measure 5-HT and MEL steady state levels. Exogenous 5-HT and MEL were used to calibrate the carbon fibre electrodes and convert current into concentration. Paired or unpaired data were compared with a t test or a one way ANOVA (P<0.05) using a Tukey-Kramer post-hoc test. Results: Amperometry studies showed that young mice had peak compression evoked release of 5-HT from combined colon and ileum of 4.9±1.5 μM while aged mice had a enhanced release of 8.1±2.9 μM and aged mice treated with melatonin were significally depressed compared to aged mice (4.3±1.0 μM; P=004). Steady state levels of 5-HT after compression from combined tissue were 5.7±1.8 μM in young tissue while aged mice (4.8±0.6 μM) and aged mice treated with melatonin were no different from young mice (3.2±0.6 μM). DPV studies showed that young mice had concentrations of 5-HT of 4.1±1.1 μM in the ileum and 5.9±2.4 μM in the colon. Concentrations of MEL were 5.3±1.6 μM in the ileum and 4.7±1.5 μM in the colon (all n=6). Compared to young mice, the steady state levels of 5HT and MEL were increased in aged mice (combined ileum and colon: 5-HT=144% and MEL=127% of young mice). In contrast, the melatonin-treated mice had lower steady state levels compared to young mice (5-HT=89% andMEL=74%).When aged mice were compared directly with aged mice treated with melatonin, there was a significant decrease in both 5HT and MEL in the treated combined tissues (P=0.001); however, when ileum and colon were examined separately only MEL was significantly decreased in the ileum (P=0.04; n= 6) and colon (P=0.02; n=6) of treated mice. Conclusions: Our data show that the availability of 5-HT and melatonin are increased in aged mice and that melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine.

W1932 Melatonin Supplementation Suppresses Serotonin and Melatonin Availability in Aged Mouse Intestine

Purpose: Aging is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during aging. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of aging. Methods: Female young mice (2-5 month; n=6), aged mice (~21 months; n=6) and aged mice treated with melatonin (~21 months; n=6; 10mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin (MEL) concentrations near the mucosal surface of ileum and distal colon. Amperometry was used to record compression evoked 5-HT while cyclic voltammetry was used to identify peaks for 5-HT and MEL. Differential pulse voltammetry (DPV: 500/800mV) was used to measure 5-HT and MEL steady state levels. Exogenous 5-HT and MEL were used to calibrate the carbon fibre electrodes and convert current into concentration. Paired or unpaired data were compared with a t test or a one way ANOVA (P<0.05) using a Tukey-Kramer post-hoc test. Results: Amperometry studies showed that young mice had peak compression evoked release of 5-HT from combined colon and ileum of 4.9±1.5 μM while aged mice had a enhanced release of 8.1±2.9 μM and aged mice treated with melatonin were significally depressed compared to aged mice (4.3±1.0 μM; P=004). Steady state levels of 5-HT after compression from combined tissue were 5.7±1.8 μM in young tissue while aged mice (4.8±0.6 μM) and aged mice treated with melatonin were no different from young mice (3.2±0.6 μM). DPV studies showed that young mice had concentrations of 5-HT of 4.1±1.1 μM in the ileum and 5.9±2.4 μM in the colon. Concentrations of MEL were 5.3±1.6 μM in the ileum and 4.7±1.5 μM in the colon (all n=6). Compared to young mice, the steady state levels of 5HT and MEL were increased in aged mice (combined ileum and colon: 5-HT=144% and MEL=127% of young mice). In contrast, the melatonin-treated mice had lower steady state levels compared to young mice (5-HT=89% andMEL=74%).When aged mice were compared directly with aged mice treated with melatonin, there was a significant decrease in both 5HT and MEL in the treated combined tissues (P=0.001); however, when ileum and colon were examined separately only MEL was significantly decreased in the ileum (P=0.04; n= 6) and colon (P=0.02; n=6) of treated mice. Conclusions: Our data show that the availability of 5-HT and melatonin are increased in aged mice and that melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine.

Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementation

Ageing is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin (EC) cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during ageing. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of ageing. Female young mice (2-5 month; n = 6), aged mice (22-24 months; n = 6) and aged mice treated with melatonin (n = 6; 10 mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin concentrations near the mucosal surface of ileum and distal colon. Amperometry studies showed that steady state levels of 5-HT from ileum and colon were decreased in aged mice treated with melatonin when compared to aged mice, while compression-evoked 5-HT release was unchanged. Differential pulse voltammetry studies showed that young mice had concentrations of 5-HT of 4.8 +/- 0.8 mum in the ileum and 4.9 +/- 1.0 mum in the colon. Concentrations of melatonin were 5.7 +/- 1.4 mum in the ileum and 5.6 +/- 1.9 mum in the colon. Compared to young mice, the levels of 5-HT and melatonin were increased in aged mice (combined ileum and colon: 5-HT = 130% and melatonin = 126% of young mice) and decreased in melatonin-treated mice (5-HT = 94% and melatonin = 82%). In conclusion, our data show that the availability of gut 5-HT and melatonin is increased in aged mice and melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine.

P4.12 Electrochemical measurements of mouse intestinal serotonin and melatonin: Effects of age and daily melatonin supplementation

Aging is associated with subtle changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin cells containing serotonin (5-HT) and melatonin may play an important role in maintaining gut function during aging. Our aim was to characterise the mucosal levels of 5-HT and melatonin in a mouse model of aging.

Severe Acute Pancreatitis: Nutritional Management in the ICU

Patients with acute pancreatitis have elevated nutritional needs due to increased energy expenditure and catabolism. It is a clinical challenge to provide adequate nutrition to these patients while maintaining gut function, preventing pancreatic stimulation, and minimizing the risk of septic and metabolic complications associated with nutritional support. We present the case of a patient who had severe acute pancreatitis and was initially given total parenteral nutrition. After a period of initial improvement, he developed hyperglycemia, bacteremia, and sepsis. Parenteral nutrition was discontinued and infection was treated with antibiotics. Subsequent nutritional support consisted of enteral feeding with an elemental diet infused via a nasojejunal feeding tube. His condition improved gradually and he made a full recovery. This case illustrates the difficulties encountered while managing a case of severe acute pancreatitis and provides an evidence based approach to the nutritional management of severe acute pancreatitis in the intensive care unit setting.

EARLY NUTRITIONAL SUPPORT IN CRITICAL ILLNESS IS IMPORTANT

The hypermetabolic state in critically ill patients is characterized by wasting of lean body mass and immunosuppression. The gut is among the most metabolically active organs. Failure to maintain gut function by way of early enteral nutrition can lead to increased infectious complications. Early enteral nutrition improves outcomes and may maintain muscle mass by blunting the cytokine-mediated hypermetabolic response.