PURPOSE AND SIGNIFICANCE EXPERIMENTAL DESIGN / METHODS EXERCISE-ASSOCIATED HYPONATREMIA: THE EFFECTS OF CARBOHYDRATE AND HYDRATION STATUS ON IL-6, ADH, AND SODIUM CONCENTRATIONS. Kimberly A. Hubing1, Laura R. Quigg1, John T. Bassett1, Melody D. Phillips1, James J. Barbee2, and Joel B. Mitchell1 FACSM, 1 Texas Christian University, 2JPS Health Network, Ft. Worth, TX. TCU Kinesiology Ex. Phys. Lab ABSTRACT Exercise-associated hyponatremia (serum sodium < 135 mmol/L) is a rare, but serious condition that has been identified in those engaging in prolonged, physical activity conducted in the heat.  PURPOSE:  The purpose of this study was to evaluate the effect of hydration status and glycogen level on plasma IL-6, ADH, and sodium concentrations during and after prolonged exercise in the heat.  METHODS:  Ten male participants completed four trials: a glycogen depleted, euhydrated condition (DE); a glycogen depleted, dehydrated condition (DD); a glycogen loaded, euhydrated condition (LE); and a glycogen loaded, dehydrated condition (LD) consisting of cycling 90 minutes at 60% VO2 max in a 35˚C environment followed by a 3-h rehydration (RH) period. During RH, subjects received either 150% of fluid lost (DD & LD) or an additional 50% of fluid lost (DE & LE).  Exercise and RH blood samples were analyzed for glucose, IL-6, ADH, and Na+.  Sweat and urine samples were analyzed for [Na+].  RESULTS: Post-exercise to post-rehydration [Na+] changes for LD, DD, DE and LE were -6.85, -6.7, -1.45 and 0.10 mM, respectively.  Post-exercise [IL-6] for DD, LD, DE, and LE were 5.4, 4.0, 3.7, and 3.49 pg/mL, respectively.  Post-exercise [ADH] for LD, DD, DE, and LE were 21.5, 12.8, 7.6, and 1.9 pg/mL, respectively.  The number of hyponatremic measurements for all RH samples was 5, 5, 20, and 10 for LD, DD, DE, and LE, respectively. CONCLUSION:  Despite our glycogen and hydration manipulations, no regulatory effects of IL-6 and ADH on plasma sodium were observed. The timing of fluid intake did alter plasma sodium since euhydration during exercise combined with an additional 50% intake during RH, and a post-exercise RH volume of 150% of fluid lost both resulted in sodium concentrations below initial levels. PURPOSE AND SIGNIFICANCE To evaluate the effect of hydration status and glycogen level on venous IL-6, ADH, and sodium concentrations during and after prolonged exercise in the heat. Observed Post-rehydration Total Body Sodium vs. Theoretical Post-rehydration Total Body Sodium. CONCLUSIONS Despite the glycogen, hydration, and exercise manipulations, no relationship between IL-6, Na+, and ADH was observed. Glycogen status had no significant impact on IL-6 and ADH concentrations. A volume of 100% fluid replacement during exercise, and a rehydration volume of 150% of fluid lost during exercise, were enough to cause a tendency toward decreased plasma sodium concentrations after each condition. In the euhydrated conditions, the decrease in sodium at the end of exercise did not recover; thus, our short-term model demonstrates the ease with which hyponatremic tendencies can be achieved. In the dehydrated conditions, the similar level of sodium at the end of rehydration suggests that hyponatremic tendencies can also be achieved with excessive post-exercise water consumption. These responses could possibly be more pronounced with longer duration and more intense exercise such as a marathon or ultra-endurance triathlon. The data from this study supports the proposed idea of osmotically inactive sodium stores within the body since the observed post-rehydration plasma sodium levels were substantially higher than the theoretically calculated sodium concentrations. Further investigation may be required with more severe exercise conditions to fully elucidate the effects of IL-6 on ADH and plasma sodium concentrations. Supported by a grant from the Gatorade Sports Science Institute RESULTS Plasma Sodium Responses. The @ indicates a significant hydration by time interaction. (p=0.02) Plasma IL-6 Responses. The  indicates time point is significantly different from all time points except 180. The † indicates time point is significantly different from 120 and 180. (p=0.00) Plasma ADH Responses. The * indicates time point at which euhydrated conditions are significantly different from dehydrated conditions. (p=0.00) EXPERIMENTAL DESIGN / METHODS Participants: 10 endurance-trained males (mean VO2 max 3.61 L·min-1, 24.2  7.6 years, and 9.28  4.88% body fat). Conditions: glycogen depleted + dehydration (DD); glycogen depleted + euhydration (DE); glycogen loaded + dehydration (LD); and a glycogen loaded + euhydration (LE). Experimental Design: Depletion ride 2 days prior to each trial. During this 2 day period subjects ate a high CHO diet (8 g CHO/kg; glycogen loaded) or a low CHO diet (0.5 g CHO/kg; glycogen depleted). The experimental condition consisted of 90 min of cycling at 60% VO2 max in a 35˚C, 40% relative humidity environment. In the dehydrated conditions (DD & LD) no water was received during exercise but water was consumed during the 3 hour recovery period to restore 150% of fluid loss during exercise. In the euhydrated conditions (DE & LE) water was consumed at 15 minute intervals to maintain 0% body weight loss with an additional 50% consumed during the 3 hour recovery period. Measurements: Blood samples (IL-6, ADH, and Na+ concentrations): pre-exercise, 45 min into exercise, immediately post exercise, every 30 minutes during the recovery period. Sweat samples – 45 minutes into exercise and during last 5 min of exercise Core temperature (throughout) Heart rate (throughout) Urine samples – during the rehydration period Statistics: The effect of hydration status, CHO status, and time on plasma sodium, ADH, and IL-6 data were analyzed using a three factor analysis of variance (ANOVA) with repeated measures. Newman-Keuls post hoc test. Significance was accepted at the p < 0.05 level. BACKGROUND Hyponatremia = serum sodium concentrations < 135 mEq/L. Symptoms include: gastrointestinal distress such as bloating and nausea, vomiting, wheezing, headaches, swollen extremities, fatigue, confusion, and lack of coordination. Severe hyponatremia can cause seizures, coma, and death. Abnormal fluid retention, possibly due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), may contribute to hyponatremia Antidiuretic hormone (ADH) is stimulated primarily by hyperosmolality and conserves water in the body by inhibiting its release into the urine. The cytokine IL-6 may also play a role in the development of hyponatremia since it is thought to be a nonosmotic stimulator of ADH.