Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress.

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 approximately 37 degrees C or heated over 90 min to a core body temperature of approximately 41, approximately 41.5, or approximately 42.5 degrees C. Permeability was greater in the 42.5 degrees C group compared with the 37, 41, or 41.5 degrees 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 degrees C compared with 37 degrees 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.

Intestinal fluid absorption during exercise: role of sport drink osmolality and [Na+].

The purpose of this study was to evaluate the effects of modifying the osmolality and [Na+] of orally ingested rehydration beverages during exercise on intestinal absorption in the duodenum and upper jejunum. Six subjects randomly ingested (23 mL.kg-1 BW) the following 6% carbohydrate solutions with and without Na+ during 85-min of cycle exercise (65% VO2 peak) in a cool (22 degrees C, 40% RH) environment: a) 0 Na+, 245 mOsm.kg-1; b) 20 mEq Na+, 283 mOsm.kg-1; c) 20 mEq Na+, 169 mOsm.kg-1; d) 50 mEq Na+, 275 mOsm.kg-1; and e) 50 mEq Na+, 176 mOsm.kg-1. To alter solution osmolality and maintain carbohydrate concentration constant, glucose, sucrose, fructose, and maltodextrin were used in different combinations. Nasogastric and multilumen tubes were fluoroscopically placed in the stomach and intestine, respectively, to simultaneously determine gastric emptying and intestinal absorption as previously described (Lambert et al., Int. J. Sports Med.17:48, 1996). Gastric emptying was not different among solutions and averaged 13 +/- 0.5 mL.min-1. Net fluid absorption was not different among beverages nor between duodenum and jejunum (x = 10.8 +/- 1.6 and 7.9 +/- 1.1 mL.cm-1.h-1, respectively). Mean osmolality increased significantly (P < 0.05) from the duodenum to the jejunum (242 +/- 6 and 293 +/- 7 mOsm.kg-1, respectively) but did not differ among solutions. These data provide evidence that a hypotonic 6% carbohydrate beverage with 50 mEq.L-1 Na+ did not enhance intestinal fluid absorption or attenuate the decline in plasma volume during exercise more than an isotonic carbohydrate-electrolyte solution or a hypotonic carbohydrate solution without sodium.

Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages.

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.

Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia.

This work tested the hypotheses that splanchnic oxidant generation is important in determining heat tolerance and that inappropriate.NO production may be involved in circulatory dysfunction with heat stroke. We monitored colonic temperature (T(c)), heart rate, mean arterial pressure, and splanchnic blood flow (SBF) in anesthetized rats exposed to 40 degrees C ambient temperature. Heating rate, heating time, and thermal load determined heat tolerance. Portal blood was regularly collected for determination of radical and endotoxin content. Elevating T(c) from 37 to 41.5 degrees C reduced SBF by 40% and stimulated production of the radicals ceruloplasmin, semiquinone, and penta-coordinate iron(II) nitrosyl-heme (heme-.NO). Portal endotoxin concentration rose from 28 to 59 pg/ml (P < 0.05). Compared with heat stress alone, heat plus treatment with the nitric oxide synthase (NOS) antagonist N(omega)-nitro-L-arginine methyl ester (L-NAME) dose dependently depressed heme-.NO production and increased ceruloplasmin and semiquinone levels. L-NAME also significantly reduced lowered SBF, increased portal endotoxin concentration, and reduced heat tolerance (P < 0.05). The NOS II and diamine oxidase antagonist aminoguanidine, the superoxide anion scavenger superoxide dismutase, and the xanthine oxidase antagonist allopurinol slowed the rates of heme-.NO production, decreased ceruloplasmin and semiquinone levels, and preserved SBF. However, only aminoguanidine and allopurinol improved heat tolerance, and only allpourinol eliminated the rise in portal endotoxin content. We conclude that hyperthermia stimulates xanthine oxidase production of reactive oxygen species that activate metals and limit heat tolerance by promoting circulatory and intestinal barrier dysfunction. In addition, intact NOS activity is required for normal stress tolerance, whereas overproduction of.NO may contribute to the nonprogrammed splanchnic dilation that precedes vascular collapse with heat stroke.

Rat small mesenteric artery function after hindlimb suspension.

To determine whether simulated microgravity in rats is associated with vascular dysfunction, we measured responses of isolated, pressurized mesenteric resistance artery segments (157- to 388-microm ID) to vasoconstrictors, pressure, and shear stress after 28-day hindlimb suspension (HS). Results indicated no differences between HS and control (C) groups in 1) sensitivity or maximal responses to vasoconstrictors (norepinephrine, phenylephrine, serotonin, KCl); 2) ID, external diameter, or ratio of wall thickness to ID; 3) distensibility; or 4) vasodilatory responses to shear stress. Myogenic tone was attenuated (P < 0.05) in HS arteries vs. C, as evidenced by 1) decreased magnitude of tone in larger vessels (second-order branch off superior mesenteric artery, 261- to 388-microm ID) at pressures >/=40 mmHg in the presence of phenylephrine (10(-7) M) and 2) decreased magnitude of tone in smaller vessels (third-order branch off superior mesenteric artery, 157- to 277-microm ID), which exhibited spontaneous tone, at pressures > or =70 mmHg. This attenuation of myogenic tone after HS could contribute to orthostatic intolerance because myogenic tone contributes to the overall tone of resistance arteries.

Splanchnic tissues undergo hypoxic stress during whole body hyperthermia.

Exposure of conscious animals to environmental heat stress increases portal venous radical content. The nature of the observed heat stress-inducible radical molecules suggests that hyperthermia produces cellular hypoxic stress in liver and intestine. To investigate this hypothesis, conscious rats bearing in-dwelling portal venous and femoral artery catheters were exposed to normothermic or hyperthermic conditions. Blood gas levels were monitored during heat stress and for 24 h following heat exposure. Hyperthermia significantly increased arterial O2 saturation, splanchnic arterial-venous O2 difference, and venous PCO2, while decreasing venous O2 saturation and venous pH. One hour after heat exposure, liver glycogen levels were decreased approximately 20%. Two hours after heat exposure, the splanchnic arterial-venous O2 difference remained elevated in heat-stressed animals despite normal Tc. A second group of rats was exposed to similar conditions while receiving intra-arterial injections of the hypoxic cell marker [3H]misonidazole. Liver and intestine were biopsied, and [3H]misonidazole content was quantified. Heat stress increased tissue [3H]misonidazole retention 80% in the liver and 29% in the small intestine. Cellular [3H]misonidazole levels were significantly elevated in intestinal epithelial cells and liver zone 2 and 3 hepatocytes and Kupffer cells. This effect was most prominent in the proximal small intestine and small liver lobi. These data provide evidence that hyperthermia produces cellular hypoxia and metabolic stress in splanchnic tissues and suggest that cellular metabolic stress may contribute to radical generation during heat stress.

Heat acclimation does not alter rat mesenteric artery response to norepinephrine.

Previous studies have shown that heat acclimation raises the temperature threshold for heat-induced splanchnic vasoconstriction in the rat (W. Haddad and M. Horowitz. Thermal Balance in Health and Disease, Advances in Pharmacological Sciences. Basel: Birkhauser, 1994, p. 203-208; M. Shochina, W. Haddad, U. Meiri, and M. Horo-witz. J. Therm. Biol. 21: 289-295, 1996). We tested the hypothesis that heat acclimation alters splanchnic resistance artery sensitivity to norepinephrine (NE). Male Sprague-Dawley rats (n = 5) were acclimated to 35 degreesC ambient temperature for 5-8 wk. Control rats (n = 5) were maintained at 22-23 degreesC ambient temperature for 5-7 wk. Small mesenteric artery segments (2- to 3-mm length, 100- to 340-micrometer ID) were isolated, cannulated at both ends, and pressurized to 50 mmHg. Artery luminal diameter was measured in response to cumulative doses of NE (10(-9) to 10(-5) M) by using video microscopy. NE dose response was measured at 37 and 43 degreesC bath temperatures. There were no differences in constriction responses to NE between acclimated and control rat arteries at either 37 or 43 degreesC. We conclude that acclimation does not alter rat mesenteric artery sensitivity to NE.

Intestinal permeability in runners in the 1996 Chicago marathon.

Abdominal cramping, nausea, diarrhea, and GI bleeding are often reported in long-distance runners. This study set out to determine the effects of prolonged (2-4 hrs) exercise and NSAID ingestion on gastric and intestinal permeability during the first 5 hrs following the 1996 Chicago Marathon. Thirty-four healthy volunteers (20 M, 14 F; ages 30-50) completed the race and ingested the test solution (5 g sucrose, 5 g lactulose, 2 g rhamnose, in 40 ml water) within 10-15 min. The urinary excretion ratio of lactulose/rhamnose was used to assess small intestine permeability; sucrose excretion was used to evaluate gastric impairment. There were no significant differences for mean training mileage, postrace rectal temperature, and percent dehydration between runners who ingested NSAIDs and those who did not. In all, 75% of subjects reported aspirin or ibuprofen ingestion before or during the race. Runners who ingested ibuprofen had significant elevations in urinary lactulose excretion and lactulose/rhamnose ratio, whereas those who ingested aspirin or who did not ingest either NSAID had no significant differences in urinary excretion of lactulose, rhamnose, sucrose, or lactulose/rhamnose ratio compared to resting controls. Thirteen of the 26 NSAID users and 4 of the 8 non-users reported GI symptoms. It is concluded that (a) ibuprofen but not aspirin ingestion during prolonged exercise may increase gastrointestinal permeability and lead to GI symptoms, and (b) prolonged exercise alone can produce GI symptoms.

Effect of estrogen supplementation on exercise thermoregulation in premenopausal women.

This study examined the effects of 3 days of estrogen supplementation (ES) on thermoregulation during exercise in premenopausal (20-39 yr) adult women during the follicular phase of the menstrual cycle. Subjects (11 control, 10 experimental) performed upright cycle ergometer exercise at 60% of maximal O2 consumption in a neutral environment (25 degreesC, 30% relative humidity) for 20 min. Subjects were given placebo (P) or beta-estradiol (2 mg/tablet, 3 tablets/day for 3 days). All experiments were conducted between 6:30 and 9:00 AM after ingestion of the last tablet. Heart rate, forearm blood flow (FBF), mean skin temperature, esophageal temperature (Tes), and forearm sweat rate were measured. Blood analysis for estrogen and progesterone reflected the follicular phase of the menstrual cycle. Maximal O2 consumption (37.1 +/- 6.2 in P vs. 38.4 +/- 6.3 ml. kg-1. min-1 in ES) and body weight-to-surface area ratio (35.58 +/- 2.85 in P vs. 37.3 +/- 2.7 in ES) were similar between groups. Synthesis of 70-kDa heat shock protein was not induced by 3 days of ES. Neither the threshold for sweating (36.97 +/- 0.15 in P vs. 36.90 +/- 0.22 degreesC in ES), the threshold for an increase in FBF (37.09 +/- 0. 22 in P vs. 37.17 +/- 0.26 degreesC in ES), the slope of sweat rate-Tes relationship (0.42 +/- 0.16 in P vs. 0.41 +/- 0.17 in ES), nor the FBF-Tes relationship (10.04 +/- 4.4 in P vs. 9.61 +/- 3.46 in ES) was affected (P > 0.05) by 3 days of ES. We conclude that 3 days of ES by young adult women in the follicular phase of their menstrual cycle have no effect on heat transfer to the skin, heat dissipation by evaporative cooling, or leukocyte synthesis of 70-kDa heat shock protein.

Effect of beverage osmolality on intestinal fluid absorption during exercise.

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.

Effect of hypohydration on gastric emptying and intestinal absorption during exercise.

Dehydration and hyperthermia may impair gastric emptying (GE) during exercise; the effect of these alterations on intestinal water flux (WF) is unknown. Thus the purpose of this study was to determine the effect of hypohydration ( approximately 2.7% body weight) on GE and WF of a water placebo (WP) during cycling exercise (85 min, 65% maximal oxygen uptake) in a cool environment (22 degrees C) and to also compare GE and WF of three carbohydrate-electrolyte solutions (CES) while the subjects were hypohydrated. GE and WF were determined simultaneously by a nasogastric tube placed in the gastric antrum and via a multilumen tube that spanned the duodenum and the first 25 cm of jejunum. Hypohydration was attained 12-16 h before experiments by low-intensity exercise in a hot (45 degrees C), humid (relative humidity 50%) environment. Seven healthy subjects (age 26.7 +/- 1.7 yr, maximal oxygen uptake 55.9 +/- 8.2 ml . kg-1 . min-1) ingested either WP or a 6% (330 mosmol), 8% (400 mosmol), or a 9% (590 mosmol) CES the morning following hypohydration. For comparison, subjects ingested WP after a euhydration protocol. Solutions ( approximately 2.0 liters total) were ingested as a large bolus (4.6 ml/kg body wt) 5 min before exercise and as small serial feedings (2.3 ml/kg body wt) every 10 min of exercise. Average GE rates were not different among conditions (P > 0.05). Mean (+/-SE) values for WF were also similar (P > 0.05) for the euhydration (15.3 +/- 1.7 ml . cm-1 . h-1) and hypohydration (18.3 +/- 2.6 ml . cm-1 . h-1) experiments. During exercise after hypohydration, water absorption was greater (P < 0.05) with ingestion of WP (18.3 +/- 2. 6) and the 6% CES (16.5 +/- 3.7), compared with the 8% CES (6.9 +/- 1.5) and the 9% CES (1.8 +/- 1.7). Mean values for final core temperature (38.6 +/- 0.1 degrees C), heart rate (152 +/- 1 beats/min), and change in plasma volume (-5.7 +/- 0.7%) were similar among experimental trials. We conclude that 1) hypohydration to approximately 3% body weight does not impair GE or fluid absorption during moderate exercise when ingesting WP, and 2) hyperosmolality (>400 mosmol) reduced WF in the proximal intestine.

Fluid and carbohydrate replacement during intermittent exercise.

Most studies relating to fluid replacement have addressed the problem of drinking during prolonged exercise. Fluid replacement is also very important for intermittent exercise, although it has not been extensively studied. More studies in this area would help coaches and athletes understand the importance of fluid balance and carbohydrate supplementation during intermittent exercise. Based on available data, it can be concluded that: (i) because of high exercise intensity, sweat loss and glycogen depletion during intermittent exercise are at least comparable with those during continuous exercise for a similar period of time. Therefore, the need to ingest a sport drink or replacement beverage during intermittent exercise may be greater than that during continuous exercise in order to maintain a high level of performance and to help prevent the possibility of thermal injury when such activity occurs in a warm environment; (ii) the volume of ingested fluid is critical for both rapid gastric emptying and complete rehydration; and (iii) osmolality (250 to 370 mOsm/kg), carbohydrate concentration (5 to 7%), and carbohydrate type (multiple transportable carbohydrates) should be considered when choosing an effective beverage for rehydration and carbohydrate supplementation during intermittent exercise.

Fructose transport mechanisms in humans.

BACKGROUND & AIMS: The possible mechanisms of fructose transport are diffusion, a disaccharidase-related transport system, and glucose-facilitated fructose transport. However, these mechanisms in the human small intestine have not been systematically examined. This study was designed to investigate the mechanisms of fructose transport in the human duodenojejunum. METHODS: A triple-lumen tube was fluoroscopically positioned in the duodenojejunum of 7 men. Nine carbohydrate-electrolyte solutions were perfused at the rate of 15 mL/min. Acarbose and lactulose were used to examine the disaccharidase-related transport system and glucose-facilitated fructose transport, respectively. RESULTS: Fructose absorption was greater (P < 0.05) from fructose-glucose (FruGlu) and fructose-glucose-acarbose (FruGluA) solutions than from fructose-mannitol (FruMann) and fructose-mannitol-acarbose (FruMannA) solutions, but there was no difference between FruGlu and FruGluA solutions. A sucrose solution produced greater (P < 0.05) sucrose absorption than a sucrose-acarbose solution. Lactulose absorption (0.016-0.039 mmol.h-1.cm-1) was observed from solutions containing glucose or sucrose. Water absorption was not different among sucrose, FruGlu, and glucose solutions. FruMann solution produced net water secretion. These data suggest that free fructose and glucose transport were not inhibited by acarbose and that the presence of glucose induced lactulose absorption and enhanced fructose absorption. CONCLUSIONS: Fructose is transported transcellularly by facilitated diffusion and paracellularly (based on lactulose transport) via glucose-activated solution drag. In the human small intestine, free fructose and glucose transport does not occur via the disaccharidase system.

Absorption from different intestinal segments during exercise.

This study evaluated intestinal absorption from the first 75 cm of the proximal small intestine during 85 min of cycle exercise [63.6 +/- 0.7% peak O2 consumption (VO2 peak)] while subjects ingested either an isotonic carbohydrate-electrolyte beverage (CHO-E) or a water placebo (WP). The CHO-E beverage contained 117 mM (4%) sucrose, 111 mM (2%) glucose, 18 meq Na+, and 3 meq K+. The two experiments were performed a week apart by seven subjects (6 men and 1 woman; mean VO2 peak = 53.5 +/- 6.5 ml . kg-1 . min-1). Nasogastric and multilumen tubes were fluoroscopically positioned in the gastric antrum and duodenojejunum, respectively. Subjects ingested 23 ml/kg body weight of the test solution, 20% (383 +/- 11 ml) of this volume 5 min before exercise and 10% (191 +/- 5 ml) every 10 min thereafter. By using the rate of gastric emptying (18.1 +/- 1.1 vs. 19.2 +/- 0. 7 ml/min for WP and CHO-E, respectively) as the rate of intestinal perfusion, intestinal absorption was determined by segmental perfusion from the duodenum (0-25 cm) and jejunum (25-50 and 50-75 cm). Water flux was different (P < 0.05) between solutions in the 0- to 25- and 25- to 50-cm segments for WP vs. CHO-E (30.7 +/- 2.7 vs. 15.0 +/- 2.9 and 3.8 +/- 1.1 vs. 11.9 +/- 3.3 ml . cm-1 . h-1, respectively). Furthermore, water flux differed (P < 0.05) for WP in a comparison of the 0- to 25- to the 25- to 50-cm segment. Total solute flux (TSF) was not significantly different among segments for a given solution or between solutions for a given segment. There was no difference between trials for percent change in plasma volume. These results indicate that 1) fluid absorption in the proximal small intestine depends on the segment studied and 2) solution composition can significantly effect water absorption rate in different intestinal segments.

Upper limit for intestinal absorption of a dilute glucose solution in men at rest.

We studied gastric and intestinal function by gastric intubation/intestinal perfusion in six healthy male volunteers to evaluate optimal use of a 6% glucose-electrolyte (GES) solution. Gastric volume, residual volume, emptying rate, and secretion were measured for an initial 763 +/- 19 ml gastric load of GES and at the beginning and end of four additional gastric loads (2.2 ml.kg-1; approximately 180 ml) given at 10-min intervals. The relatively high gastric (713 +/- 58 ml) and residual (507 +/- 26 ml) volumes maintained a high gastric emptying rate (19.5 +/- 1.4 ml.min-1). Composition of the GES emptied into the duodenum was also measured in this first experiment. In a second experiment, this modified solution was infused (triple lumen tube) into the duodenum at a rate equal to gastric emptying rate, or at 38 or 77% greater rates. Absorption of water (11.3-12.9 ml.h-1.cm-1) and glucose 4.3-5.6 mmol.h-1.cm-1) were similar at all perfusion rates during the second experiment. We conclude that duodenojejunal segmental absorption rates of water and glucose produced by a rapid, sustained gastric emptying rate cannot be increased by delivering a greater load of glucose and water by intestinal perfusion.

Effect of running intensity on intestinal permeability.

Enhanced intestinal permeability has been associated with gastrointestinal disorders in long-distance runners. The primary purpose of this study was to evaluate the effect of running intensity on small intestinal permeability by using the lactulose and rhamnose differential urinary excretion test. Secondary purposes included assessing the relationship between small intestinal permeability and gastrointestinal symptoms and evaluating gastric damage by using sucrose as a probe. Six healthy volunteers [5 men, 1 woman; age = 30 +/- 2 yr; peak O2 uptake (VO2peak) = 57.7 +/- 2.1 ml.kg-1.min-1] rested or performed treadmill exercise at 40, 60, or 80% VO2peak for 60 min in a moderate environment (22 degrees C, 50% relative humidity). At 30 min into rest or exercise, the permeability test solution (5 g sucrose, 5 g lactulose, 2 g rhamnose in 50 ml water, approximately 800 mosM) was ingested. Urinary excretion rates (6 h) of the lactulose-to-rhamnose ratio were used to assess small intestinal permeability, and concentrations of each probe were determined by using high-performance liquid chromatography. Running at 80% VO2peak increased (P < 0.05) small intestinal permeability compared with rest, 40, and 60% VO2peak with mean values expressed as percent recovery of ingested dose of 0.107 +/- 0.021 (SE), 0.048 +/- 0.009, 0.056 +/- 0.005, and 0.064 +/- 0.010%, respectively. Increases in small intestinal permeability did not result in a higher prevalence of gastrointestinal symptoms, and urinary recovery of sucrose did not reflect increased gastric permeability. The significance and mechanisms involved in increased small intestinal permeability after high-intensity running merit further investigation.

Gastrointestinal permeability following aspirin intake and prolonged running.

We sought to evaluate the effects of exercise and aspirin on gastroduodenal and intestinal permeability. Seven volunteers (age = 29 +/- 3 yr, VO2max = 56.8 +/- 4.1 ml.kg-1.min-1) rested or performed treadmill exercise (60 min at approximately 68% VO2max), with or without aspirin ingestion. Placebo (glucose) or aspirin (1.3 g) was taken the night before and prior to rest or exercise (total 2.6 g). A permeability test solution (approximately 1300 mOsm.kg-1), containing 10 g lactulose (L), 5 g mannitol (M), and 10 g sucrose (S), was ingested prior to rest or exercise. Urinary excretion rates (6.h-1), expressed as a percentage of ingested dose, were used to quantify intestinal (L/M ratio) or gastroduodenal (S) permeability. Ingestion of aspirin before running increased (P < 0.05) intestinal permeability compared to placebo+running and placebo+rest, but not compared to aspirin+rest; mean (+/-SE) values for the L/M ratio were 0.248 +/- 0.046, 0.029 +/- 0.012, 0.012 +/- 0.004, and 0.104 +/- 0.057, respectively. Gastroduodenal permeability following aspirin+running (3.25 +/- 1.21%) was also elevated (P < 0.05) compared to placebo+running (0.43 +/- 0.15%) and placebo+rest (0.24 +/- 0.11%), but not compared to aspirin+rest (0.66 +/- 0.27%). Neither running nor aspirin ingestion was associated with gastrointestinal (GI) complaints. Thus, GI permeability while running can be markedly elevated by aspirin ingestion.

Reexamination of tympanic membrane temperature as a core temperature.

Controversies surrounding tympanic temperature (Tty) itself and techniques for measuring it have dampened the potential usefulness of Tty in determining core temperature (operationally defined here as the body temperature taken at a deep body site). The present study was designed to address the following questions. 1) Can a tympanic membrane probe be made that is safer and more reliable than its predecessors? 2) Why is the effect of facial cooling and heating on Tty so inconsistent in reports from different laboratories? 3) Is Tty still useful as a measure of core temperature? Data from this study, obtained with a modified thermocouple probe, suggest that the widely reported facial skin cooling effect on Tty is most probably due to thermal contamination from the surrounding ear canal wall and/or suboptimal contact of the probe sensor with the tympanic membrane because 1) Tty that fell during facial cooling was increased to the precooling level by the repositioning of the probe sensor; 2) Tty determined by using a probe with a larger sensor area (the sensor soldered to a steel wire ring)tended to fall in response to facial cooling, whereas Tty determined with a thermally insulated probe ring did not; and 3) Tty obtained under careful positioning of the insulated probe was relatively insensitive to facial cooling or heating. Because Tty was practically identical to esophageal temperature (Tes) in the steady state, i.e., 36.83 +/- 0.20 (SD) degrees C for Tty and 36.87 +/- 0.16 degrees C for Tes at room temperature (n = 11), and because facial cooling had little effect on both Tty and Tes (36.86 +/- 0.17 degrees C for Tty and 36.86 +/- 0.26 degrees C for Tes during facial or scalp skin cooling), we support the postulate that Tty is a good measure of core temperature. The temperature transient in response to foot warming was detected 5 min (n = 2) faster with Tty than with Tes. Thus, with further improvements in the design of the probe. Tty can become a standard for determination of core body temperature.

Paracellular transport of water and carbohydrates during intestinal perfusion of protamine in the rat.

With these experiments, the authors' purpose was to determine whether the intestinal perfusion of protamine would successfully block paracellular transport without causing significant change in cardiovascular function. In anesthetized (50 mg x kg-1 sodium pentobarbital) rats (n=12), heart rate and mean arterial blood pressure were measured during perfusion (0.5 mL x min-1) of a carbohydrate-electrolyte solution through the small intestine. The carbohydrate-electrolyte solution contained 150 mM glucose, 150 mM fructose, 10 mM lactulose, 17 mEq sodium, 3 mEq potassium, and either 0.0, 0.1, 1.0, or 10 mg x mL-1 protamine. Osmolality of the 4 solutions ranged from 363 +/- 2 to 365 +/- 3 mOsm x kg-1. Core temperature was maintained at 37 degrees C in an environmental chamber. Heart rate and mean arterial blood pressure were constant during all intestinal perfusions. Forty-one percent of the perfused lactulose was absorbed. Absorption of glucose, fructose, and lactulose was significantly inhibited by 0.1 mg x mL-1 protamine, while water absorption was decreased 41 percent by 1.0 mg x mL-1 protamine. Water and lactulose absorption fell 75% with protamine, and glucose and fructose absorption fell 50%. Lactulose and fructose absorption did not decrease further when protamine dose rose to 10 mg x mL-1. These results indicate that 1) perfusion of protamine into the small intestine in doses that significantly affect intestinal transport does not significantly affect heart rate and mean arterial blood pressure; and 2) if the primary effect of protamine is to block paracellular movement of water and solute, the greater protamine inhibition of water and lactulose absorption is consistent with a greater paracellular transport of water and lactulose than for glucose and fructose.