Intestinal barrier dysfunction, endotoxemia, and gastrointestinal symptoms: the 'canary in the coal mine' during exercise-heat stress?

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.

Effect of exercise intensity on active and passive glucose absorption.

The purpose of this study was to determine the effects of exercise intensity on active and passive intestinal glucose absorption. Eight trained runners (age = 23 +/- 2 y; VO2max = 62.1 +/- 5.8 mL x kg(-1) x min(-1)) performed a 1 h resting experiment and three 1 h treadmill experiments at 30, 50, or 70% VO2max in a thermoneutral environment. Immediately prior to each experiment, euhydrated subjects ingested a solution containing two non-metabolizable glucose analogs, 3-O-methyl-D-glucose (3MG; actively absorbed; 5 g) and D-xylose (passively absorbed; 5 g). During the following 5 h, all urine was collected and the amount of 3MG and D-xylose in the urine was determined. Using repeated measures ANOVA, a significant (P < 0.05) reduction in urinary excretion of each carbohydrate was observed at 70% VO2max compared to the other intensities suggesting that both active and passive intestinal absorption of glucose may be reduced during prolonged running at this intensity.

Gastric emptying and intestinal absorption of a low-carbohydrate sport drink during exercise.

The purpose of this study was to determine if lowering carbohydrate (CHO) concentration in a sport drink influences gastric emptying, intestinal absorption, or performance during cycle ergometry (85 min, 60% VO(2peak)). Five subjects (25 +/- 1 y, 61.5 +/- 2.1 mL . kg(-1) . min(-1) VO(2peak)) ingested a 3% CHO, 6% CHO, or a water placebo (WP) beverage during exercise. Gastric emptying was determined by repeated double sampling and intestinal absorption by segmental perfusion. Total solute absorption and plasma glucose was greater for 6% CHO; however, neither gastric emptying, intestinal water absorption, or 3-mi time trial performance (7:58 +/- 0:33 min, 8:13 +/- 0:25 min, and 8:25 +/- 0:29 min, respectively, for 6% CHO, 3% CHO, and WP) differed among solutions. These results indicate lowering the CHO concentration of a sport drink from 6% CHO does not enhance gastric emptying, intestinal water absorption, or time trial performance, but reduces CHO and total solute absorption.

Tumor necrosis factor-alpha hyper-responsiveness to endotoxin in whole blood is associated with chronic bronchitis in farmers.

Many farmers experience chronic bronchitis, airflow obstruction, and asthma. It is thought that these respiratory problems may be related to workplace inhalation of organic dust containing endotoxin. The purpose of this study was to determine whether whole blood cytokine responsiveness to endotoxin is associated with airflow disorders (i.e., airflow obstruction, chronic bronchitis, and doctor-diagnosed asthma). Farmers (N = 95) were recruited from a rural cohort study and completed a respiratory symptom and history questionnaire, spirometry, and blood sampling. Blood was incubated 24 hours in the presence and absence of endotoxin and supernatants were analyzed for TNF-alpha, IL-1beta, IL-6, and IL-8. Hypo- or hyper-responsiveness to endotoxin was based on whether cytokine values were in the lower or upper 10% of the group range, respectively. A significant association existed between TNF-alpha hyper-responsiveness and chronic bronchitis. These results indicate that the whole blood cytokine assay may be useful to identify individual responsiveness to endotoxin, and may provide an additional diagnostic tool to evaluate persons potentially at risk for developing chronic bronchitis following exposure to organic dust in the workplace.

Polymorphisms in the CD14 gene associated with pulmonary function in farmers.

RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers.

Role of gastrointestinal permeability in exertional heatstroke.

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.