The intestinal barrier is formed by enterocyte membranes, tight junctions, secreted mucus, and immunologic factors, such as tissue macrophages. Dysfunction of this barrier can be caused by different types of stress (e.g., physiological, pathological, psychological, pharmacological) and can lead to increased intestinal permeability. Increased permeability to endotoxin, a component of the walls of gram-negative bacteria, causes local or systemic inflammatory reactions, or both. The immune response(s) can then promote more serious conditions. Exertional heat stroke is an example of such a condition. During severe exercise-heat stress, possibly combined with other stresses, reductions in intestinal blood flow, direct thermal damage to the intestinal mucosa, or both, can cause intestinal barrier disruption and endotoxemia. The resulting inflammatory response is believed to be involved in altered thermoregulation and multiple-organ dysfunction. Possible means for preventing or attenuating, or both, many stress-induced intestinal barrier problems include environmental, pharmaceutical, or nutritional approaches, or a combination of these.

-The purpose of this study was to characterize intestinal permeability changes over a range of physiologically relevant body temperatures in vivo and in vitro. Initially, FITC-dextran (4,000 Da), a large fluorescent molecule, was loaded into the small intestine of anesthetized rats. The rats were then maintained at ϳ37°C or heated over 90 min to a core body temperature of ϳ41, ϳ41.5, or ϳ42.5°C. Permeability was greater in the 42.5°C group compared with the 37, 41, or 41.5°C groups. Histological analysis revealed intestinal epithelial damage in heated groups. Everted intestinal sacs were then used to further characterize hyperthermia-induced intestinal permeability and to study the potential role of oxidative and nitrosative stress. Increased permeability to 4,000-Da FITC-dextran in both small intestinal and colonic sacs was observed at a temperature of 41.5-42°C compared with 37°C, along with widespread intestinal epithelial damage. Administration of antioxidant enzyme mimics or a nitric oxide synthase inhibitor did not reduce permeability due to heat stress, and tissue concentrations of a lipid peroxidation product were not altered by heat stress, suggesting that oxidative and nitrosative stress were not likely mediators of this phenomenon in vitro. In conclusion, hyperthermia produced increased permeability and marked intestinal epithelial damage both in vivo and in vitro, suggesting that thermal disruption of epithelial membranes contributes to the intestinal barrier dysfunction manifested with heat stress. intestine; heat stress; free radicals; nitric oxide; FITC-dextran

Posm accurately identifies a state of euhydration and is sensitive to changes in hydration status during acute dehydration and rehydration. Usg and Uosm are also sensitive to changes in hydration status but lag behind during periods of rapid body fluid turnover and therefore correlate only moderately with Posm during acute dehydration.

Reduced splanchnic blood flow and hyperthermia during exercise-heat stress can produce gastrointestinal barrier dysfunction and increased gastrointestinal permeability. This may allow endotoxin to enter the internal environment, causing local and systemic immune responses. These responses may be involved in the cause and outcome of exertional heatstroke. Countermeasures may reduce gastrointestinal permeability and possibly exertional heatstroke occurrence and outcome.

Reduced intestinal blood flow and high intestinal temperatures during exercise-heat stress can lead to intestinal barrier dysfunction. Such dysfunction may increase intestinal permeability to endotoxin. During exercise-heat stress, intestinal barrier dysfunction and endotoxemia can produce gastrointestinal symptoms and increased production of pro-inflammatory cytokines. Such problems may be a warning sign ('canary in the coal mine') for the onset of exertional heat stroke. Failure to heed such a warning may culminate in problems indicative of exertional heat stroke such as circulatory collapse and multiple organ failure. Prior exposure to exercise-heat stress may, however, be a protective mechanism.

The purpose of this study was to determine whether aspirin (A) ingestion combined with prolonged exercise increases gastrointestinal permeability and whether consumption of a carbohydrate-containing (CHO) or a CHO + glutamine-containing (CHO+G) beverage would reduce this effect. Seventeen subjects completed six experiments. They ingested A (1,300 mg) or placebo (P) pills the evening before and before running 60 min at 70% maximal oxygen uptake. Also, before running they ingested a solution containing 5 g lactulose (L), 5 g sucrose (S), and 2 g rhamnose (R). During each trial, either a 6% CHO beverage, a 6% CHO+G (0.6%; 41 mM) beverage, or a water placebo (WP) was consumed. For 4 h after a run, all urine was collected to measure urinary excretion of L, R, and S. S excretion (percentage of dose ingested; measure of gastroduodenal permeability) was significantly greater (P < 0.05) during the A trial while the subjects drank the WP compared with all other trials. Administration of A also significantly increased L/R (measure of intestinal permeability) for the CHO and WP trials compared with all P trials. Ingestion the CHO or CHO+G beverages significantly reduced S excretion and L excretion when A was administered, but it did not reduce L/R. These results indicate that gastroduodenal and intestinal permeability increase after A ingestion during prolonged running and that ingestion of a CHO beverage attenuates the gastroduodenal effect but not the intestinal effect. Furthermore, addition of G to the CHO beverage provided no additional benefit in reducing gastroduodenal or intestinal permeability.

The purpose of this study was to determine gastrointestinal (GI) permeability during prolonged treadmill running (60 min at 70 % V.O2max) with and without fluid intake (3 ml/kg body mass/10 min). Twenty runners (11 males, 9 females; age = 22 +/- 3 (SD) yrs; mean V.O2max = 55.7 +/- 5.0 ml/kg/min) completed four experiments: 1) rest, 2) running with no fluid (NF), 3) running with ingestion of a 4 % glucose solution (GLU), and 4) running with ingestion of a water placebo (PLA). To determine GI permeability, subjects also drank a solution containing 5 g sucrose (S), 5 g lactulose (L), and 2 g rhamnose (R) immediately prior to each trial. Gastroduodenal permeability was determined by urinary S excretion, while small intestinal permeability was determined by the L/R excretion ratio. Percent body mass loss (i.e., dehydration) was negligible during rest, GLU and PLA, while NF resulted in a 1.5 % loss of body mass (p < 0.05). Gastroduodenal and intestinal permeability were significantly (p < 0.008) increased in NF compared to rest. There were no other differences in GI permeability. These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels.

To determine how osmolality of an orally ingested fluid-replacement beverage would alter intestinal fluid absorption from the duodenum and/or jejunum during 85 min of cycle exercise (63.3 +/- 0.9% peak O2 uptake) in a cool environment (22 degreesC), seven subjects (5 men, 2 women, peak O2 uptake = 54.5 +/- 3.8 ml . kg-1 . min-1) participated in four experiments separated by 1 wk in which they ingested a water placebo (WP) or one of three 6% carbohydrate (CHO) beverages formulated to give mean osmolalities of 197, 295, or 414 mosmol/kgH2O. CHO solutions also contained 17-18 meq Na+ and 3.2 meq K+. Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested a total of 23 ml/kg body mass of the test solution, 20% (370 +/- 9 ml) of this volume 5 min before exercise and 10% (185 +/- 4 ml) every 10 min thereafter. By using the rate of gastric emptying as the rate of intestinal perfusion (G. P. Lambert, R. T. Chang, D. Joensen, X. Shi, R. W. Summers, H. P. Schedl, and C. V. Gisolfi. Int. J. Sports Med. 17: 48-55, 1996), intestinal absorption was determined by segmental perfusion from the duodenum (0-25 cm) and jejunum (25-50 cm). There were no differences (P > 0.05) in gastric emptying (mean 18.1 +/- 1.3 ml/min) or total fluid absorption (802 +/- 109, 650 +/- 52, 674 +/- 62, and 633 +/- 74 ml . 50 cm-1 . h-1 for WP, hypo-, iso-, and hypertonic solutions, respectively) among beverages; but WP was absorbed faster (P < 0.05) from the duodenum than in the jejunum. Of the total volume of fluid ingested, 82 +/- 14, 74 +/- 6, 76 +/- 5, and 68 +/- 7% were absorbed for WP, hypo-, iso-, and hypertonic beverages, respectively. There were no differences in urine production or percent change in plasma volume among solutions. We conclude that total fluid absorption of 6% CHO-electrolyte beverages from the duodenojejunum during exercise, within the osmotic range studied, is not different from WP.