Effects of cycle exercise on intestinal in humans

absorption

C. V. GISOLFI, K. J. SPRANGER, R. W. SUMMERS, H. P. SCHEDL, AND T. L. BLEILER Department of Exercise Science and Gastroenterology, University of Iowa, Iowa City, Iowa 52242 GISOLFI, C. V., K. J. SPRANGER,R. W. SUMMERS,H. P. SCHEDL,AND T. L. BLEILER. Effects ofcyck exerciseon intestinal absorption in humans. J. Appl. Physiol. 71(6): 2518-2527, 1991.-Intestinal absorption was measuredin six trained male cyclists during rest, exercise,and recovery periodswith the segmental perfusion technique. Each subjectpasseda multilumen tube into the duodenojejunum.The experiments consistedof I) a sequenceof l-h bouts of cycling exercise at 30, 50, and 70% maximal 0, uptake (TO .2m,) separatedby l-h rest periodsor 2) a 90-min bout at 70%VO,~,. The cycling wasperformed on a constant-load Velodyne trainer. Absorption of water and a 6% carbohydrate-electrolyte (2% glucose,6% sucrose,20 meqNa+, 2.6 meq K+) solution (both perfused at 15 ml/min) were compared. The effects of perfusing an isotonic electrolyte solution during mild (30%VO, m,) exercisewere also studied. Fluid was sampledevery 10 min from ports 10 and 50 cm distal to the infusion site. Water flux wasdeterminedby differences in polyethylene glycol concentration acrossthe 40-cm test segment. Resultsshowed1) no difference in water or electrolyte absorption rates among rest, exercise, and recovery periods; 2) no difference in absorption rates amongthe three exerciseintensities or different exercisedurations; and 3) significantly greater fluid absorption rates from the carbohydrate-electrolyte (CE) solution than from water. Water flux during rest, exercise,and recovery was about sixfold greater from the CE solution than from the isotonic solution without carbohydrate. We conclude that I) exercisehas no effect on water or solute absorption in the duodenojejunum,2) fluid absorption occurs significantly faster from a CE solution than from water, and 3) fluid absorption is increasedsixfold by addition of carbohydrate to an electrolyte solution.

water absorption; catecholamines

IN THE 194Os, Adolf and colleagues

(1) recognized the

emptying characteristics of fluid replacement solutions, because gastric emptying was believed to be the factor limiting rehydration. The influence of oral rehydration solutions (ORS) and exercise on gastric emptying has been the subject of several recent reviews (10, 29,34). In contrast, intestinal absorption of ORS in exercising humans has rarely been studied, and the control mechanisms involved are poorly understood. The few studies that have been conducted show that intestinal absorption increases (32), decreases (45), or does not change (19) with exercise. These disparate results could be attributed to differences in I) mode, duration, or intensity of exercise, 2) ambient temperature, 3) method employed to measure absorption, 4) segment of the intestine studied, and/or 5) formulation of the test solution. This study was designed to eliminate many of these ambiguities by examining the effects of exercise intensity and duration on small bowel absorption of select beverages with the use of the more direct technique of segmental perfusion of the duodenojejunum. We addressed two primary questions: 1) Does cycling exercise at 30,30, and 70% maximal 0, uptake (VO,~~J for 1 h or 70% Vozmax for 1.5 h alter the rate of duodenojejunal absorption of water and an isotonic ORS? 2) Are fluid and electrolytes absorbed faster from a carbohydrate-electrolyte (CE) solution than from water? We also investigated the effects of mild exercise on intestinal absorption of an isotonic solution without carbohydrate. We hypothesize that 1) exercise will reduce fluid absorption during perfusion of either distilled water or a 6% CE solution relative to rest; 2) fluid and electrolyte absorption will be significantly greater during perfusion of the CE solution throughout rest, exercise, and recovery than during the perfusion of water; and 3) an isotonic solution containing carbohydrate will be absorbed significantly faster than one formulated without added carbohydrate.

importance of fluid replacement during and after exercise. They reported that humans must replace the fluid lost in sweat to avoid “dehydration exhaustion” while working in the heat (I). At the same time, Christensen EXPERIMENTAL DESIGN AND METHODS and Hansen (7) observed a significant increase in work time to exhaustion of men who ingested a high-carbohySix well-trained male cyclists volunteered to particidrate diet for 3-7 days before exercise. This suggested pate in this investigation. Each provided informed signed that carbohydrates were an essential fuel during proconsent and had previously participated in an intestinal longed heavy exercise (5). Others found that the ability absorption study in this laboratory. The project was apto perform heavy exercise is dependent on initial muscle proved by our Human Use and Radiation Protection glycogen concentration (2, 24) and that muscle glycogen Committees. depletion contributes to exhaustion when endurance exEach subject completed four paired experiments that ercise is performed (5). Furthermore, Bergstrom (5) demcompared test solutions of distilled water and an isotonic onstrated that intravenous infusion of glucose during exercise decreased muscle glycogen utilization. These early findings stimulated research on the gastric 2518

CE solution (Table 1). The pair of shorter experiments, designated as design I, were 4 h in duration: 1.5 h of rest, 1,5 h of cycling at 70% VO, max, and 1 h of recovery. The

0161-7567191 $1.50 Copyright 0 1991 the American Physiological Society

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

EXERCISE

1. Composition

AND ABSORPTION

IN HUMANS

2519

The first 30 min on the bicycle served as a control period for HR, T, , and plasma volume (PV). After mountPEG, ??a+, Osmolality, K+, ing his bike, the subject calibrated the Velodyne commosmol/kg Solution mg/ml meq/l meq/l puter. This was a 1-min procedure in which he pedaled to 25 mph, coasted to 5 mph, and then pedaled back to 25 6% CE l.ltO.03 24.6t0.74 2.4t0.17 283.3t3.05 Water l*lt0.1 26.4k2.92 mph. He then sat quietly in cycling position while the Isotonic-electrolyte 0.9205 139t3 5.ltO.l 295.320.70 mouthpiece for the metabolic cart was adjusted and electrocardiogram (ECG) leads (Red Dot disposable ECG Values are means ,t SE. PEG, polyethylene glycol; CE, carbohydrate-electrolyte solution. Anions were not measured directly; howleads) were attached. At the end of the 30-min control ever, 6% CE (2% glucose, 4% sucrose) contained (in meq) 11.5 chloride, period, a 12-ml blood sample was drawn, and HR and T, 6.5 citrate, and 3.2 phosphate, and isotonic-electrolyte solution conmeasurements were recorded. The subject then distained 144 meq chloride. mounted and sat on a high laboratory stool. Infusion of the test solution was started, and clocks were reset. pair of design I1experiments were 7.5 h in length: 1.5 h of The subject remained on the stool for the 1st h of each rest, 1 h of cycling at 30% VOW,,, 1 h of rest, a 2nd h of experiment and during all subsequent rest periods. At cycling at 50% VoZmm, 1 h of rest, a 3rd h of cycling at the end of each rest period, a clothed weight was obtained 70% vo2 m8x, and a final 1 h of rest. To control for possi- before the subject mounted his bicycle and initiated ble effects of previous cycling bouts and perfusion time pedaling at the set intensity. Throughout each experion intestinal absorption, each subject performed the ment, blood samples were taken every 30 min; HR and T, three intensities in different orders. However, the same were recorded every 15 min. Intestinal fluid was sampled order of intensity was maintained when water and the at lo-min intervals from the proximal port at the rate of CE solution were perfused. In a separate series of experi1 ml/min and was drained by siphoning from the distal ments, five subjects cycled at 30% VO, maxwhile an iso- port. During the exercise bout, measurements of i7O,, tonic solution (Table 1) without carbohydrate was per- minute ventilation (VE), and respiratory exchange ratio fused (1.5 h of rest, 1 h of exercise, 1 h of recovery). (RER) were made in addition to the other measurements Fluid absorption in the duodenojejunum was deterpreviously described. After completing 60 or 90 min of mined by segmental perfusion, as previously described exercise, the subject dismounted his bicycle, stepped on (21). This technique involves the constant (15 ml/min) the scale for a clothed-weight measurement, and reperfusion of the test substance through one lumen of a turned to the laboratory stool for the subsequent recovmultilumen catheter and sampling from two distal sites. ery period. Fluid absorption was determined by quantitating the Methods. T, was measured with a thermistor probe change in concentration of polyethylene glycol (PEG), a connected to a telethermometer (model 44Ta, Yellow nonabsorbable marker, in the test segment by use of the Springs Instrument); HR was determined from ECG tracequations of Cooper et al. (8). The initial [PEG] in both ings. Clothed body weight was measured on an Acme solutions was 1 g/l. scale accurate to ztll0 g. Total body sweat rate (SR) for Protocol. Before the absorption experiments, VO, maX each exercise period was calculated from the net change was determined by use of a progressive treadmill exercise in clothed body weight corrected for fluid infused, blood test to exhaustion. A Velodyne trainer (Schwinn Bicycle) and intestinal fluid withdrawn, and urine excreted. attached to the subject’s bicycle was employed to deterBlood samples were analyzed for hemoglobin (Hb) mine the work loads required to elicit 30, 50, and 70% concentration (525-2, Sigma Chemical) and hematocrit . vo 2max. The Velodyne trainer is a constant-load device (Hct) in quadruplicate. Relative changes in PV (% APV) and was used in all subsequent experiments. O*nce the from preexercise values were calculated from mean Hb work load that required 70% of the subject’s VO, was and Hct values, as described by Dill and Costill (15). determined, he cycled at that intensity for 90 min to be- Plasma and intestinal samples were analyzed for glucose come familiar with the protocol. Measurements of heart (glucose analyzer model 23A, Yellow Springs Instrurate (HR), core temperature (T,), and 00, maxwere made ment), osmolality (model 5300, Wescor), and [Na”] and during this exercise bout. After the subject completed the [K+] (flame photometer model 143, International Labo9O-min ride successfully, he was scheduled for the four ratory). In design I, plasma samples were also analyzed paired experiments. for catecholamines (42). In addition, intestinal samples On the night before an experiment, the subject was were analyzed for [PEG] by use of the Hyden techinstructed to eat a carbohydrate-rich meal before 10 P.M. nique (26). Statistics. For each measured variable, data from the and to ingest only water thereafter. At 7 A,M, he reported two designs were analyzed separately. A two-factor reto the University of Iowa Hospitals and Clinics for posipeated-measures analysis of variance (ANOVA) was tioning of the multilumen tube by use of fluoroscopy. The infusion port was positioned lo-15 cm beyond the used to determine differences between the solutions, differences over time, and solution-by-time interaction. If pyloric sphincter. A needle catheter attached to a threethere were no significant differences over time, no differway stopcock filled with heparinized saline was inserted in a superficial arm vein. The subject then walked to the ence between solutions, and no significant interaction, Exercise Physiology Laboratory, donned his biking gear data from both solution trials were pooled and a one-factor ANOVA and Scheffg’s F test were used to determine (shorts, socks, and biking shoes), inserted a rectal probe, had a clothed weight determined, and mounted his whether there were significant differences among rest, exercise, and recovery. If there were significant interacbicycle. TABLE

of solutions perfused

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

2520

EXERCISE

AND ABSORPTION

2. Cardiovascular and thermoregulatory responsesduring experimental designs

TABLE

HR, beatdmin

%, ml kg-’ l

Design

l

Sweat

min-’

%VO2,

Rate,

ml /min

I

Carbohydrateelectrolyte

70% vo2ms Water

165t5

53.2t3.1

72.8t3.0

22.6kl.l

70% vo2mar

164t5

52.1t4.3

71.4t3.5

23.ltl.O

Design Carbohyrateeleqtrolyte 30% V02mm 50% vo2,,, 70% irOam Water 30% vo2*&50% vo2mar 70% vo,,

II

115+6 149t5.2 171t5

22.5tl.l 38.8t2.3 54.2k2.5

30.0t0.9 52.4+2 73.1k2.4

11.8k1.3 19.4kl.l 22.9t0.8

108*8 136t6.4 165t7.4

21.2tl 35.2t2.4 51.824.3

29.3t0.3 48.722 71.2t3.6

10.6t2 19.0tl 22.7tl.2

Values are means t SE. HR, heart rate; Vo,, 0, uptake; voz,,, maximal 0, uptake.

IN HUMANS

lutions tested with the segmental perfusion technique (with a triple-lumen tube) is not the composition of the solutions perfused. As each solution moves through the mixing segment, it blends with intestinal secretions and forms a homogeneous solution by the time it reaches the proximal sampling site (21). Perhaps the best indication of the composition of the solution being tested is the mean of the values determined from samples collected at the proximal and distal sampling sites. The change in composition of the solutions used in this study, as they perfused the mixing and test segments, has been described previously (21). Neither exercise intensity nor exercise duration (60-90 min) affected net water movement across the duodenojejunum (Fig. 1, Table 3). Net fluid absorption showed very little variation during rest, exercise, and recovery periods for either solution trial. Because there were no differences over time or among rest, exercise, and recovery periods, the data in design I were pooled to determine differences between solution trials. This analysis showed a greater (P < 0.05) fluid absorption rate during perfusion of the 6% CE (-12.0 t 1.4 ml h-l cm-l) solution than during the perfusion of water (-8.1 t 0.93 l

tion effects, a one-factor repeated-measures ANOVA and Scheffk’s F test were performed on the data from each solution trial to determine whether there were significant differences among rest, exercise, and recovery for a specific solution. Also, a one-factor ANOVA was performed to determine at which time solutions differed for each measured variable. In addition, a correlation matrix over time was computed for each parameter to determine whether the compound symmetry assumption was met. Compound symmetry holds if the correlations between measures taken at different times are relatively constant for all pairs of time points. Meeting this assumption allows us to use the repeated-measures ANOVA with a greater degree of confidence. If this assumption is violated, the degrees of freedom for the resulting F tests must be reduced (46).

m

l

Exercise Rest Recmwy ;_ .” . . ,‘: . . 3.:. .’ _,: : ,. y . . /:,:.’ ,..: ‘. .. ..:.I : .. : ...: :~., - ._ .,::I( )‘ ._.... ,, :‘.. .:: : : . . . :. ,._ .i .I” .: _.;;._ j:. ,_ .’ _. ., _.,.,.:‘ _.? : I) *,“-l,l ‘, L:Gi.ii:a.c;... Y ” - - - - - - - - - -----‘-LI)I-CLI;LL-LI:.

RESULTS

The results from the two experimental designs are presented together because the changes observed were similar. The data were first analyzed over time within the periods of rest, exercise, and recovery. If no significant differences were found, the data were pooled to yield single values for rest, exercise, and recovery. If significant differences were not observed among these three time periods, the latter values were pooled and analyzed for differences between solution trials. The subjects in this study were highly trained endurance cyclists; some werenationally ranked. Their mean age, weight, height, and VO, lllaXwere 25.2 t 1.2 yr, 75.2 t 3.2 kg, 178.1 t 3.4 cm, and 74.9 t 2.0 ml. kg-l min-‘, respectively. All worked at the desired exercise intensity in both designs. Mean values for VU,, HR, T,, and SR were not different between the two solution trials in either experimental design (Table 2). HR and T, rose significantly (P < 0.05) during each exercise bout. There were no significant differences in HR, T,, or Vo, between design I and design II cycling bouts at 70% VO, mBx. It is important to note that the composition of the sol

Time in Minutes FIG.

1. Design

11 net water

flux

during

perfusion

of water

or 6%

carbohydrate-electrolyte

(CE) solution (means t SE) at rest, during 60 at 30, 50, and 70% maximal C& uptake (VOW,&, and

min of exercise during 60 min of recovery.

Infusion

began

at time 0. Negative

values

indicate absorption. Note that net water flux values were all greater (more negative) during perfusion of 6% GE solution than during perfusion of water.

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

EXERCISE

AND ABSORPTION

3. ‘Water and electrolyte flux acruss the duodenojejunum and select blood chemistries during rest, exercise, and recouery for design I experiments

TABLE

Rest Inks

Water flux, ml. h-l. cm-l 6% CE Water K+ flux, meq h-l cm-l 6% CE Water Na’ flux, meq . h-’ cm-l 6% CE Water l

Exercise

Recovery

flux:

tinal

-13.2t1.9 -85t0.8

-11.5t1.8 -8.021.5

-11.9-t-0.9 -7.8t1.2

-0.04,tO.O2 0.00+0.01

-0.06tO.01 -0.02t,0.01

-0.04tU.01 -0*01t0.01

-0.48t,O.19 -0.18tO.07

-0.331~0.18 -0.38&O. 12

-0.47kO.17 -0.44&O. 15

88.2t1.7

119.2-1-5.7

l

l

Plasma

Plasma glucose, mg/lOO ml 6% CE Water Plasma osmolality, mosmol/kg 6% CE Water Plasma K+, meq/l 6% CE Water Plasma Na+, meq/l

values

112.1k9.7 89.4t2.1 281.6t1.9 277,623.O

91.1t3.6

80.43-2.4

285.3H.7 282.1t4.1

278.7~41.4

271.223.9

3.6kO.2

4.520.2

3.8t0.3

4.1t0.2

4.720.1

4.120.3

6% CE

142.4t1.2

143.6kl.O

142.5k1.7

Water

142.4t1.3

142.420.6

140.4t0.5

6.5tl.2

-3.lk1.5

10.31-t-1.4*

3.2t2.0

-4.2t1.5

Final APV, 6% CE

Water

2521

IN HUMANS

solution perfused (Table 3). In design II, Na+ flux remained unchanged over time and was not different between exercise intensities (Fig. 3A); however, there was a greater (P < 0.05) Naf absorption during perfusion of the CE solution than of water (Fig. 3C). The relatively high absorption of Na+ in water is attributed to intestinal secretion. The mean [Na+] in the aspirate from the proximal sample site during rest, exercise, and recovery periods was 55.1 t 1.9 and 69.6 t 2.5 meq/l for the CE solution and water, respectively. This difference is significant. The higher [Na+] fur water is attributed to the greater concentration gradient for Na+ with water than with CE solution perfusion and reduced solvent drag from a lower mean net fluid absorption from water. During the 90-min cycling trials, net KS flux from both infusates remained stable through the exercise bout (Table 3), but the values for the CE solution were all greater (more negative) than those for water. The data were pooled over time when differences between solution trials were analyzed, because there were no differences among rest, exercise, and recovery periods. K+ was absorbed significantly faster during the CE perfusions than from the perfusion of water (Table 3). In design II, K+ flux across the duodenojejunum followed the same patRest

Recovery

Exercise

% 5.0-r-0.7

Values are means 2 SE. APV, change in plasma volume. Because there were no differences over time, data for rest, exercise, and recuvery were pooled. * Significantly different from water during recovery.

ml h-l cm-l). In design II, there were no differences in fluid absorption over time among rest, exercise, and recovery periods or with increasing exercise intensity. When data were pooled 1) over time, 2) over rest, exercise, and recovery periods, and 3) over exercise intensity, there was a significant difference in fluid absorption rates between solution trials, The CE solution was absorbed significantly faster (12.0 t 0.93 ml. h-l cm-l) than water (-8.6 t 1.18 ml. h-lo cm-l). Moreover the mean values were very similar to those observed in design I. Perfusion of each solution into the small bowel did influence PV. In design I, perfusion of water into the intestine elevated PV 3.2% at rest and 5% during recovery (Table 3). Conversely, cycling reduced PV 4.2% from preexercise volume. Infusion of the CE solution elevated PV 6.5 and 10.3% during rest and recovery, respectively, whereas cycling reduced PV only 3.1%. In design 11, the percent changes in PV were significantly different between solution trials (P < 0.05) when pooled across rest, exercise, and recovery periods; however, they were only significant at scattered data points when each time point was analyzed separately (Fig. 2). The exercise-induced decline in PV was more severe during the 50 and 70% VO 2maxcycling bouts than during the 30%x702m8Xbout regardless of the solution perfused. The latter observation is partially attributed to an increased SR associated with these work loads (Table 2). In design 1, Na+ flux was unaffected by exercise or the l

l

* e

6%CE Water

l

I 0

30

60

90

120

150

180

Time in Minutes 2. Time course of %change in plasma volume during infusion of water and 6% CE solution while subjects rested, exercised at 30,50, and 70% VOW,,, and recovered from exercise in design II. Values are means t SE. “Significantly different from rest and recovery values; ‘fsignificant difference between solution-specific trials. FIG.

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

2522

EXERCISE

AND ABSORPTION

tern as water flux. It remained stable throughout rest, exercise, and recovery periods for each exercise intensity (Fig. 3.B). There were no significant differences in K+ flux among the three exercise intensities, but K+ was absorbed significantly faster (P < 0.05) during 6% CE perfusion than during water perfusion (Fig. 3C). In a manner similar to Na+, intestinal secretions also added K+ to the perfusate. K+ concentration at the proximal sampling site averaged 5.53 t 0.27 and 2.42 t 0.58 meq/l for the CE solution and water, respectively. In design 1, perfusion of the CE solution initially elevated (P c 0.05) plasma glucose concentration, but it returned to baseline before exercise began. During exercise, glucose concentration fell in the first 30 min, returned to baseline by 60 min of exercise, and then remained stable. In recovery, it rose significantly in the first 30 min and then returned to baseline by 60 min (Table 3). Perfusion of water during the 9O-min exercise bout resulted in a slight (P < 0.05) elevation in glucose concentration during exercise. In design 11, the patterns of change in glucose concentration during perfusion of both water and the CE solution were similar to those described for design I, except there was no significant rise in glucose concentration during exercise when water was Rest’

Exercise

_I+_ 1 _Ic_

Recovery

Water25 Water 50 Water70

IN HUMANS Exercise

Recovery

L

I 0

III 30

III 60

1 90

Ill 120

II 150

180

Time In Minutes FIG. 4. Time course of plasma glucose concentration for design II experiments.

(means +_SE)

perfused (Fig. 4). The compound symmetry assumption was violated consistently for plasma glucose data; therefore the significance of these alterati .ons should be interpreted cautiously. In design I, plasma osmolality, [Na+], and [K+] were unaffected by the composition of the perfused solution; i.e., there were no differences between solution trials (Table 3). However, plasma osmolality rose significantly during exercise and fell below resting values in recovery (P < 0.05). There were no significant changes in plasma [Na+], but plasma [K+] rose significantly during exercise. As in design I, plasma osmolality, [Na+] , and [K+] in design II were unaffected by the solution perfused, so the data for both solution trials were pooled, and only the effects of exercise intensity are shown in Fig. 5. Plasma osmolality rose significantly during the 50 and 70% . VO 2 maxexercise bouts. Although plasma [K+] rose significantly during all cycling bouts, the elevation at 70% 2 lJLmwas greater (P < 0.05) than at 30 and 50% VO, m8x. There were no differences in plasma [Na+]. Figure 6 shows plasma epinephrine and norepinephrine concentrations for the design I experiments. Both catecholamines were significantly elevated above rest and recovery values during exercise at ‘70% VO, M8X.Catecholamines were not measured in design II. Figure 7 shows the results of perfusing the isotonic solution without carbohydrate during exercise at 30% . vo 2 max. Note the marked reduction in water flux during all periods compared with perfusion of the isotonic solution with carbohydrate (Fig. 1, Table 3). Although no statistically significant differences were observed, there was a trend for reduced water and electrolyte fluxes during exercise compared with rest and recovery periods. l

vu

I 0

II

I

I

30

I

I

60

I

I

I1

90

1

II

I

I20

I

150

I

t

I

180

Time in Minutes -0.203

Water

FIG. 3. Net flux (means t SE) of sodium (A) and potassium (B) during perfusions of water or 6% CE solution in design II experiments. See Fig. 1 for other details. C: net sodium and potassium flux (pooled means k SE) over rest, exercise, and recovery periods for each exercise intensity during perfusion of water and 6% CE solution. *Different from water (P < 0.05).

DISCUSSION

The primary purpose of this research was to determine whether cycling exercise at 30, 50, or 70% of V02msx altered the absorption of distilled water or a CE solution from the human duodenojejunum. We found that fluid absorption was constant throughout rest, exercise, and

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

EXERCISE Exercise

w

AND ABSORPTION

Recovery

25%

2523

IN HUMANS

Fluid absorption from an isotonic CE solution with or without electrolytes is greater than net fluid absorption from plain water (l&21,31). The present results support this observation; however, in one recent study, fluid absorption from a hypotonic solution was the same or significantly less than net fluid absorption from water (44). Why the latter investigators did not observe enhanced fluid absorption from a CE solution despite its hypotonicity is unclear, but the reason could in part be the form of carbohydrate used to formulate the solutions studied. The design of the present study was similar to that of Fordtran and Saltin (19). In both studies, absorption was measured by segmental perfusion while subjects exercised for 1 h. The major differences were that Fordtran and Saltin used treadmill exercise at 68-74% VO, IlDaXand studied the effects of several solutions in the jejunum. They observed fluid movement ranging from -7.1 (absorption) to +3.5 (secretion) ml h-l cm-’ because of the large differences in [glucose] and [Na+] concentrations among their test solutions (19). Their conclusion, that strenuous treadmill exercise had no effect on intestinal absorption, was drawn from separate analysis of each infusion. The design of the present study permitted grouped statistical analysis and clearly suggests that not only strenuous but also mild and moderate cycling exercise fail to significantly change duodenojejunal absorption. In contrast, Williams et al. (45), Maughan and Leiper (32), and Barclay and Turnberg (4) reported that exercise reduced fluid and/or active carbohydrate absorption. l

II

I

0

30

I

I

60

I

I

I

90

I

120

I

I

150

t

]

180

Time in Minutes FIG. 5. Plasma osmolality, [Na+], and [K+] (means t SE) over time for design II experiments. Values from water and CE solution trials were pooled because they were not significantly different. Plasma osmolality rose during moderate (50%) and intense (70%) exercise bouts and returned to resting levels during subsequent recovery periods. There were no significant changes in plasma [Na+] data. Plasma [KT] rose significantly during each exercise bout (P < 0.05). The 70% VO,,, exercise bout was associated with significantly greater plasma [K+] than the other 2 bouts; it dropped back to resting levels during subsequent recovery periods. *Different from recovery values of that exercise trial (P < 0.05); tdifferent from resting values (P < 0.05); #different from exercise values from 25 and 50% vo2,, trials (P < 0.05).

recovery during both water and CE trials; however, the CE solution was absorbed significantly faster than water when the data were pooled across time. Fluid absorption rates observed in the present study were similar to those reported in the literature (20). Our values for water absorption (-8.06 and -8.62 ml h-l cm-l for designs I and II, respectively, or -37 ml/IO0 ml of fluid perfused) agree with values reported by Fordtran et al. (40 ml/100 ml) (18), Wheeler and Banwell (-10.15 ml qh-l. cm-‘) (44), and a previous report from our laboratory (-9.40 ml 4h-l cm-l) (21). Lower rates were reported by Leiper and Maughan (-1.8 t 2.8 ml. h-l cm-l) (31) and Banwell et al. (-0.58 ml h-’ . cm-l) (3). The higher values cannot be attributed to higher infusion rates, because all studies had infusion rates between 9 and 15 ml/min. Perhaps construction of the multilumen tube had a role. Our tube was constructed with polyvinyl bridges around both proximal and distal ports to prevent adherence of the tube to the intestinal wall, which would limit sampling ability. l

Rest

Exercise

l

Recovery

+ llcl

6%CE Water

l

l

l

l

Time In Minutes 6. Time course of changes in plasma catecholamines (means t SE) for design I experiments. *Different (P < 0.05) from rest and recovery for both solutions. FIG.

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

2524

EXERCISE

AND ABSORPTION

-0.30

Rest

Exercise

Recovery

Condition

7. Water, sodium, and potassium flux (means k SE) during perfusion of a hypotonic electrolyte solution (see METHODS for composition) without carbohydrate. Subjects rested for 1 h, exercised at 30% % maxfor 1 h, and recovered for 1 h at rest. Note low net water flux values compared with perfusion of water and 6% CE solution (see Figs. 1 and 2). FIG.

Each of these studies involved a different technique for measuring intestinal absorption and very different experimental designs. Williams-et al. observed a reduction in plasma and urine concentrations of 3-0-methyl-D-glucase (3- MG) Yan actively transported carbohydrate, during mild exercise in the heat but no change in the plasma or urine concentration of xylose, a passively transported carbohydrate. They proposed that tissue hypoxia, resulting from an inadequate blood supply, reduced active carbohydrate absorption during mild exercise in a warm environment. Their conclusion was made on the basis of previous research indicating that exercise of a similar load reduced splanchnic blood flow (SBF) (36). It has also been reported that carbohydrate absorption falls when mucosal cells become hypoxic in vitro ( 13). On the other hand, Sjovall et al. (40) found that splanchnic nerv ‘e stimulation only reduced blood flow to the muscularis and crypts of the intestinal wal 1 without a ffecting blood flow to the villi, the absorptive site. It is conceivable that humans also maintain blood flow to the villi when SBF is compromised, and therefore absorption rate is not affected by exercise-induced changes in SBF. Attenuation of 3-MG appearance in the plasma and urine, observed by Williams et al. (45), cannot be isolated to changes in intestinal absorption. A decrease in gastric emptying may be partially responsible for the reduced

IN HUMANS

appearance of actively absorbed carbohydrate during exercise. The subjects in this study performed exercise in the heat, which has also been shown to reduce gastric emptying during exercise compared with the same exercise performed in a cool environment (35). Furthermore the study by Williams et al. involved the entire bowel rather than a segment of the proximal small intestine. Thus it is difficult to compare the results of this study with the present investigation. Maughan and Leiper (32) investigated the effect of cycling exercise on rehydration by labeling a hypotonic CE solution (200 mmol/l) with deuterium oxide (0,O). They found that the rate of plasma D,O accumulation from a beverage labeled with D,O was faster at rest (32.4 t 8.4 ppm/min) than during exercise at 61% (10.8 t 2.1 ppm/ min) or 80% (5.5 t 1.3 ppm/min) of Vo2,,, and was faster at 42% (14.8 t 3.6 ppm/min) and 61% vozrnar than at 80% voamax. Hence they concluded that strenuous exercise reduced the availability of fluid ingested during exercise. In this study, as in the report by Williams et al. (45), the stomach and entire small bowel were evaluated; therefore, attenuated rates of gastric emptying and/or intestinal absorption could have produced the reduction in fluid availability. Moreover, it remains controversial whether the rate of D,O accumulation in the plasma is a valid measure of net fluid movement from the duodenojejunum into the blood. In a recent study in which this technique was used, we found that the accumulation of D,O in the plasma could not distinguish between solutions that were absorbed or secreted (21). Barclay and Turnberg (4) employed segmental perfusion and observed that exercise decreased fluid absorption in the duodenojejunum. Absorption was measured during l-h periods of rest, exercise, and recovery. The mean HR of their subjects during exercise (103 beats/ min) was similar to the mean HR (112 beats/min) of our subjects when they exercised at 30% VO, m8X.The composition of the solution infused in the two studies, however, was markedly different. Barclay and Turnberg perfused an isotonic electrolyte solution that consisted of 136 mM Na+, 105 mM Cl-, 5 mM K+, and 5 g/l PEG with 5 mCi/l of [l*C]PEG. Our perfusates in designs I and II were either isotonic or contained both carbohydrate and Na? Barclay and Turnberg reported fluid absorption rates of only -1.28, -0.65, and -0.95 ml h-l cm-l for rest, exercise, and recovery, respectively. When we investigated the effects of rest and exercise on absorption of the same isotonic electrolyte solution, we found similarly low fluid absorption rates and the same trend for exercise to reduce absorption but no significant difference among rest, exercise, and recovery values (Fig. 7). The small decrease in absorption during mild exercise reported by Barclay and Turnberg (4) was statistically significant but probably of little biological importance. The absence of carbohydrate in their perfusate reduced fluid absorption and may have unmasked the inhibitory effect of mild exercise on intestinal absorption (4, 14). However, it is crucial to point out that the addition of carbohydrate increases fluid absorption ~6. to lo-fold. We did not observe a decrease in fluid absorption while subjects cycled at 30% Voamax during the infusion of water because of the greater variability in our data. l

l

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

EXERCISE

AND ABSORPTION

Water absorption is dependent on solute absorption, and the proximal bowel does attempt to bring luminal [Na+] to 140-150 meq/l. This process probably attenuates fluid absorption during the perfusion of water at rest enough to nullify any significant effect of exercise. Changes in gastrointestinal transit time, nerve activity, and plasma catecholamine concentration associated with exercise may participate in determining the rate of duodenojejunal fluid absorption. Many athletes report the urge to defecate after exercise (16,39), and exercise is commonly recommended as therapy for constipation in sedentary adults (25,38); however, defecation is a colonic function, and little is known about the effects of exercise on the large bowel. Accelerated transit through the small intestine during mild exercise has been documented in only one study (27); it is unknown what effects moderate or severe exercise has on small bowel motility. Transit rate does not appear to influence small bowel absorption (33), perhaps because exchange across the mucosal cell is so fast that, even under conditions of reduced contact time with the absorbing mucosa, there is still time for complete exchange. Elevated plasma catecholamines and increased sympathetic nerve activity (SNA) appear to influence the rate of intestinal electrolyte and fluid transport. Both in vitro and in vivo evidence support sympathetic control of intestinal transport. Animal studies in which sympathetic nerve supply to the small intestine was sectioned or stimulated indicate that the sympathetic nervous system exerts a basal inhibitory effect on cholinergically mediated intestinal secretion and thus promotes absorption (6, 40). Intravenous isoproterenol injections into humans significantly (P < 0.05) increased absorption of Na+, Cl-, and water in both the jejunum and ileum, whereas ,& blockade with intravenous propranolol significantly reduced jejunal electrolyte absorption and induced ileal water and Na+ secretion (33). However, changes in plasma catecholamine concentration and SNA have not been measured simultaneously with intestinal absorption during exercise; hence the role of SNA associated with exercise on intestinal absorption is unknown. We measured plasma catecholamine concentration in design I (70% 90, maxfor 1.5 h) and found a lo-fold increase in circulating norepinephrine (NE) (1.68 rig/ml) and a 25-fold increase in plasma epinephrine (E, 230 pg/ ml) during the exercise bout (Fig. 6). These concentrations, which are similar to plasma catecholamine data previously reported during cycling at this intensity (28), presumably had no effect on duodenojejunal absorption because, during exercise, intestinal absorption did not change relative to rest and recovery. In addition to the determination of the effect of exercise itself, a secondary purpose of this study was to determine whether fluid and electrolyte absorption during exercise differed between the CE solution and distilled water. As hypothesized, fluid absorption was significantly (P < 0.05) greater during the CE infusions, even though they were an isotonic solution. This result supports previous findings in resting subjects (17, 21,30). The hypotonicity of the water probably enhanced its absorption. At the proximal sampling site, the osmolality of water was 125 and 121 mosmol/kg for designsI and II,

2525

IN HUMANS

respectively. Leiper and Maughan (30) measured fluid absorption via segmental perfusion from two hypotonic (251 mosmol/kg) and two isotonic (297 and 287 mosmol/ kg) solutions containing various concentrations of salt. Glucose concentration in these four solutions was 106, 83,59, and 140 mmol/l, respectively. Net fluid absorption from the hypotonic solutions was -11.3 and -10.6 ml h-l cm-l; absorption rates for the isotonic solutions were -5.9 and -7.6 ml h-l cm? Thus the greater fluid absorption from the hypotonic solution was attributed to the greater osmotic gradient across the mucosal membrane. K+ is passively transported in the human small bowel. It follows water movement, closely suggesting paracellular transport (41). In the CE trials ([K+] in CE is 2.4 meq/l; in water it is 0) in which fluid absorption was significantly greater than in water trials, K+ absorption was also significantly greater. Throughout the exercise bouts in which fluid absorption remained constant, K+ absorption also remained constant. [K’] absorption over rest, exercise, and recovery for water and the hypotonicelectrolyte solution averaged 2.42 k 0.58 and 5.76 t 0.06 meq/l, respectively, at the proximal sampling site. K+ absorption was about the same from these two solutions, probably because fluid absorption from the perfusion of water was ~6- to lo-fold greater than from the hypotonic electrolyte solution. Na+ absorption was not different between the two solution trials in design 1, but in design II when the data were pooled across rest, exercise, and recovery and across exercise intensity, Na+ flux was significantly greater during perfusion of the CE solution than during perfusion of water. This observation is consistent with the greater fluid absorption from the CE solution. In all solution trials, the amount of fluid entering the plasma remained stable over time, although the amounts varied for each solution. Conversely, the amount of fluid lost from the plasma increased as SR increased with the intensity of work. Exercise at 30, 50, and 70% T;To~~produced mean SR of 11.2,19.3, and 22.8 ml/min. Corresponding reductions in PV were 3-8,10-12.5, and 8-13%, respectively. Plasma [K+] and osmolality changed accordingly, being eleva!ed significantly during the cycling bouts at 50 and 70% VO, m8xand only slightly during the 3O%Vo 2max cycling bout. In addition to the progressive decline in PV, extrusion of K+ from active muscle fibers contributes to the progressive rise in plasma [K+] (12). Plasma [Na+] was not altered by any of the exercise bouts. It remained at -142 meqll in design I and 143 meq/l in design II, Plasma [Na+] typically is 138-142 meq/l and rises only l-4% during exercise from the loss of hypotonic sweat (12). The ionic concentration of sweat varies markedly among individuals and is affected by the rate of sweating and the subject’s state of heat acclimatization (9). In general, however, sweat is hypotonic, and it contains principally Na+ and Cl- (11). [Na+] in sweat ranges from 40 to 60 meq/l (11). The loss of Na+ in sweat is not the only mechanism by which plasma Na+ is altered. During prolonged exercise the body attempts to conserve Na+ by increasing the rate of renal Na+ absorption and by decreasing the [Na+] in the sweat (43). It is believed that these effects are mediated by the action of l

l

l

l

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

2526

EXERCISE

AND ABSORPTION

aldosterone in response to activation of the renin-angiotensin system (43). We conclude that mild to severe cycle exercise of 600to 9O-min duration does not influence fluid or electrolyte absorption from the duodenojejunum. Also, fluid absorption from an isotonic 6% (2% glucose-4% sucrose) CE solution is significantly greater than from distilled water and sixfold greater than from an isotonic solution without carbohydrate. Thus inclusion of carbohydrate in a rehydration solution is crucial if fluid absorption is of prime importance. This conclusion is supported by the observation that fluid absorption from a 6% carbohydrate solution without electrolytes was the same as from a 6% CE solution (18, 22). Moreover, fluid absorption from either of these solutions was greater than from water. This does not diminish the importance of Na+. The inclusion of Na+ in a rehydration solution does contribute to the maintenance of PV during exercise (23,37). From a practical viewpoint, these data indicate that drinking water alone is better than drinking water with only added electrolytes; however, if electrolytes are added to a fluid replacement beve rage, carbohydrate should also be added to enhance fluid absorption.

13. 14.

15.

16.

17. 18. 19.

IN HUMANS

and electrolyte distribution during prolonged exercise. Int. J. Sports Med. 2: 130-134,1981. DARLINGTON, W., ANDJ. QUASTEL. Absorption of sugars from isolated surviving intestine. Arch. Biochem. 43: 194-207, 1953. DAVIS,G.,C,SANTAANA,S.MOROWSKI,AND J. FORDTRAN. Inhibition of water and electrolyte absorption by polyethylene glycol (PEG). Gastroenterology 79: 35-39, 1980. DILL,D., ANDD. COSTIL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J. Appl. Physiol. 37: 247-248, 1974. F~GOROS, R. Runners trots: gastrointestinal disturbances in runners. J. Am. Med. Assoc. 243: 1743-1744, 1980. FORDTRAN, J. Stimulation of active and passive sodium absorption by sugars in the human jejunum. J. Clin. Invest. 55: 728-737,1975. FORDTRAN, J.S.,R. LEVITAN,V. BIKERMAN, ANDB.A. BURROWS. The kinetics of water absorption in the human intestine. Trans. Assoc. Am. Phys. 74: 195-206,196l. FORDTRAN, J., ANDB. SALTIN-Gastric emptying and intestinal absorption during prolonged severe exercise. J. Appl. Physiol. 23: 331-335,1967.

GIS~LFI,~.,R. SUMMERS, ANDH. SCHEDL. Intestinalabsorptionof fluids during rest and exercise. In: Perspectives in Exercise and Science and Sports Medicine. Fluid Homeostasis During Exercise, edited by C. V. Gisolfi and D. R. Lamb. Kauai, HI: Benchmark, 1989, chapt. 3, p. 129-180. 21. GISOLFI,C., R, SUMMERS, H. SCHEDL, T. BLEILER,ANDR. OPPLIGER. Human intestinal water absorption: direct vs. indirect measurements. Am. J. Fhysiol. 258 (Gustrointest. Liver Physiol. 21): 20.

G216-G222,1990.

The authors thank Professor Leon Burmeister for statistical expertise and Joan Seye for preparation of the manuscript. This research was supported by the Quaker Oats Company and the Department of Veterans Affairs Research Service. Address for reprint requests: C. V. Gisolfi, Dept. of Exercise Science, University of Iowa, Iowa City, IA 52242. Received 1 October 1990; accepted in final form 25 July 1991. REFERENCES

1. ADOLF, E. The human body and the desert. In: F%y&!ogy of Man in the Desert, edited by M. B. Visgcher, D. W. Bronk, E. M. Landis, and A+ C. Ivy. New York: Interscience, 1947, p. 16-32. 2. AHLBORG, B., J. BERGSTROM, L. EKELUND, ANDE. HULTMAN. Muscle glycogen and muscle electrolytes during prolonged physical exercise. Acta Physiol. Stand. 70: 129442, 1967. 3. BANWELL, J. G.,N. F.PIERcE,R.C.MITFW,K.L. BRIGHAM& J. CARANASOS, R. I. KEIMOWITZ,II. S. FEDSON, J. THOMAS,S. L. GORBACH, R.B. SACK,AND A. MONDAL.Intestinal fluid andelectrolyte transport in human cholera. J. Clin. Inuest. 49: 183495, 1970. 4. BARCLAY, G., ANDL. TIJRNBEBG. Effect of moderate exercise on salt and water transport in the human jejunum, Gut 29: 816-820, 1987. 5. BERGSTROM, J., L. HERMANSEN, E. HULTMAN,ANDB. SALTIN. Diet, muscle, glycogen and physical performance. Acta Physiol. &and. 71:140-150,1967. 6. BRUNSSON, I.,S. EKLUND, M. JODAL,O.LUNDGREN,ANDH. SJOVALL.The effect of vasodilation and sympathetic nerve activation of net water absorption in the cat’s small intestine, Acta Physiol. Scand. 106: 61--68,1979. 7. CHRISTENSEN, E., AND 0. HANSEN.Arbeitsfahigkeit und Ernahrung. Stand. Arch. Physiol. 81: 160-171, 1943. 8. COOPER,H., R. LEVITAN,J. FORDTRAN,AND F. INGELFINGER. A method for studying absorption of water and solute from the human small intestine. Gastroenterology 50: l-7, 1966. 9. COSTILL,D. Sweating: its composition and effects on body fluid. Ann. NY Acad. Sci. 301: 160~174,1977. 10. COSTILL, D. L. Gastric emptying of fluids during exercise. In: Perspectives in Exercise Science and Sports Medicine. Fluid Humeostasis During E;lcercise,edited by C. VI Gisolfi and D. R. Lamb. Indianapolis, IN: Benchmark, 1990, vol. 3, pa 97-127. 11. &STILL, D., R. COTE, ANDW. PINK.Muscle water and electrolytes following varied levels of dehydration in man. J. Appl. Physiol. 40: 6-11,1976.

13 AY. COSTILL,D.,E. COTE,W. FINK,ANDP.V. HANDEL. Muscle water

22.

GISOLFI,~.V.,R.D. SUMMERS, H.P. SCHEDL,AND T.L. BLEILER.

The effect of sodium concentration in a carbohydrate-electrolyte solution on intestinal absorption (Abstract). Physiologist 33: 117, 1990. 23. HARRISON, M.,R. EDWARDS,~DP. FENNESSY. Intravascularvolume and tonicity as factors in the regulation of body temperature. J, Appl. Physiol. 44: 69-75, 1978. 24. HERMANSEN, L., E. HULTMAN,ANDB. SALTIN.Muscle glycogen during prolonged severe exercise, Acta Physiol. &and. 71: 129-139, 1967. 25.

HULL,C.,R. GREW,ANDD. BROOKS. Alleviation of constipation in the elderly by dietary fiber supplementation.

J. Am. Geriatr. Sot.

28:410-414,198O. 26.

HYDEN,S. A turbidimetric method of determination of higher polyethylene glycols utilizing an emulsifier. Gastroenterology 53: 250256,1967.

27. 28.

29. 30.

31.

32.

KEELING,W., ANDB. MARTIN. Gastrointestinal transit during mild exercise. J. Appl. Physiol. 63: 978-981, 1987. KOTCHEN, T.,L. HARTLEY, T. RICE,E. MOUGEY, L. JONES,AND J. MANN. Renin, norepinephrine, and epinephrine responses to graded exercise. J. Appl. Physiol. 31: 178-184, 1971. LAMB, D., ANDG. BRODOWICZ. Optimal use of fluids of varying formulation to minimize exercise-induced disturbances in homeostasis. Sports Med. 3: 247-274, 1986. LEPER,J., ANDR. MAUGHAN.The effect of luminal tonicity on water absorption from a segment of the intact human jejunum (Abstract). J. Physiol. Land. 378: 95, 1986. LEIPER, J. B., ANDR. J. MAUGHAN. Absorption of water and electrolytes from hypotonic, isotonic and hypertonic solutions (Abstract). J. PhysiuC Land. 373: 9OP, 1986, MAUGHAN, R.J.,J. B.LEIPER,ANDB.A. MCGAW.Effectsofexercise intensity on absorption of ingested fluids in man. Exp. Physiol. 75: 419-421,199o.

MORRIS,A., ANDL. TURNBERG. Influence of isoproterenol and propranolol on human intestinal transport in vivo. Gastroenterology 81: 1076~1079,1981. 34. MURRAY, R. The effects of consuming carbohydrate-electrolyte beverages on gastric emptying and fluid absorption during and following exercise. Sports Med. 4: 322-351, 1987. 35. OWEN, M.,K. KREGEL, P. WALL,ANDC.GISOLFI. Effectsofingesting carbohydrate beverages during exercise in the heat. Med. Sci. Sports Exercise 18: 568-575,1986. 36. ROWELL, L., J. BLACKMON, ANDR. BRUCE.Indocyanine green clearance and estimated hepatic blood flow during mild exercise to maximal exercise in upright man. J. Clin. Invest. 43: 1677-1690, 33.

1964.

ANDC. V. GISOLFI. 37. RYAN, . A. J.,. T. L. BLEILER,J. E. CARTER,

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.

EXERCISE

AND ABSORPTION

Gastric emptying during prolonged cycling exercise in the heat. Med. Sci. Sports Exercise 21: 51-58, 1989. 38. SANDMAN,P., R. ADOLFSSON, G. HALLMANS, C. NYGREN, L. NYSTROM, AND B. WINBLAD. Treatment of constipation with high bran bread in long-term care of severely demented elderly patients. J. Am. Geriatr. Sot. 31: 289-292, 1983. 39. SHARMAN, I. Gastrointestinal disturbances in runners (Abstract). Br. J. Sports Med. 16: 179, 1982. 40. SJOVALL, H., S. REDFORS, D. HALLBACK, S. EKLUND, AND M. JoDAL. The effect of splanchnic nerve stimulation on blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the small intestine. Acta Physiol. Scand. 117: 359-365,1983. 41. TURNBERG, L. Potassium transport in the human small bowel. Gut 12: EM--818,1971.

IN HUMANS

42. VANORDEN,D. E., D. B. GOODALE,H. A. BAKER, D. B.

2527 FARLEY,

R. K. BHATNAGAR. Uterine catecholamines and prostaglandins during the estrous cycle of the rat. Endocrinology 106: 16501654,198O. 43. WADE,C. Response, regulation and actions of vasopressin during exercise: a review. Med. Sci, Sports Exercise 16: 506-511, 1984. 44. WHEELER, K., AND J. BANWELL. Intestinal water and electrolyte flux of glucose-polymer electrolyte solutions. 1Med. Sci. Sports Exercise 18: 436-439, 1986. 45. WILLIAMS, J., M. MAGER, AND E. JACOBSON. Relationship of mesenteric blood flow to intestinal absorption of carbohydrates. J. Lab. Clin. Med. 63: 853-863, 1964. 46. WINER, B. J. Statistical Principles in Experimental Design. New York: McGraw-Hill, 1971, p. 267. AND

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (192.236.036.029) on September 2, 2018. Copyright © 1991 American Physiological Society. All rights reserved.