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(Journal of Nutrition. 1999;129:410-418.)
© 1999 The American Society for Nutritional Sciences


Article

The Sodium Concentration of Enteral Diets Does Not Influence Absorption of Nutrients but Induces Intestinal Secretion of Water in Miniature Pigs

Hansjörg Ehrlein 1 , Benedikt Haas-Deppe and Eckhard Weber

Institute of Physiology, University of Hohenheim, Stuttgart, Germany


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Contradictory opinions exist as to whether the sodium concentration of enteral diets influences absorption of macronutrients and transepithelial movement of sodium and water. Therefore, we investigated the effects of various sodium concentrations of enteral diets on absorption of macronutrients and on net fluxes of sodium and water. In unanesthetized miniature pigs, a 150-cm jejunal segment was perfused with an oligopeptide (Peptisorb), an oligomeric and a polymeric diet. The polymeric diet was supplemented with pancreatic enzymes. The sodium concentrations varied between 30 and 150 mmol/L. The energy density was 3.4 MJ/L. The sodium concentration of the diets did not influence absorption of macronutrients and of total energy. However, increasing sodium concentrations of the diets were associated with increasing osmolality of the solutions, resulting in a linear increase in net secretion of water and flow rate of chyme. With all diets and sodium concentrations net secretion of sodium occurred. The sodium secretion was independent of the initial sodium concentration of the diets. It was linearly correlated with net flux of water and was largest in miniature pigs infused with the oligomeric diet. The sodium concentration of the jejunal effluent did not correspond to the initial sodium concentration of the diets. The present results indicate that enteral feeding of diets with high energy density inevitably increases net secretion of water and sodium as sodium concentration increases. Therefore, the sodium concentration of diets should be as low as possible to meet only the minimal daily requirement of sodium. Low sodium concentrations of diets have no negative effects on absorption of macronutrients.


KEY WORDS: • enteral nutrition • sodium • osmolality • miniature pigs • water secretion


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In the sixties,Crane et al. (1965)Citation presented the hypothesis that the intestinal absorption of glucose is coupled with the absorption of sodium and that the sodium gradient across the brush border membrane is of major importance in the transport process. Further, the uptake of both sodium and glucose across the brush border membrane of the intestinal enterocytes is caused by specific sodium-dependent glucose transporters designated as sodium-dependent glucose transporters (SGLT-1)4 (Wright et al. 1994Citation ). This implies that sodium is required for the absorption of glucose and that glucose improves the absorption of sodium. In vitro studies have clearly demonstrated that the absorption of glucose depends on the sodium concentration of the solution (Holtug and Skadhauge 1991,Citation Schultz and Curran 1970Citation ). On the other hand, the observation that glucose enhances the absorption of both sodium and water led to the use of glucose-containing electrolyte solutions for the treatment of severe secretory diarrheas (Hirschhorn et al. 1968,Citation Nalin et al. 1968Citation ). Sodium and water were intensivley investigated to improve the so-called oral rehydration solutions—the relationship between the luminal concentration of glucose and sodium that provides the optimal absorption rates of glucose, (Elliott et al. 1991,Citation Hirschhorn and Grenough 1991,Citation Hunt et al. 1992 and 1994,Citation Citation Rolston and Mathan 1990Citation ). In these glucose-electrolyte solutions the absorption of water is of major importance, whereas the supply of macronutrients and energy is of minor significance. Therefore, rehydration solutions are comprised of small amounts of glucose and are either iso-osmotic or hypo-osmotic. Water absorption was greatest with isotonic solutions containing 60 mmol sodium/L and 111–140 mmol glucose/L, i.e., when the glucose-sodium ratio is ~2 (Elliott et al. 1991Citation ).

In contrast to the application of rehydration solutions, the aim of enteral feeding is to administer the daily energy supply without a surplus of water. Therefore, enteral diets are characterized by complex and concentrated substrates, resulting in a high energy density. The luminal degradation of carbohydrates and proteins by pancreatic enzymes is associated with a marked increase in osmolality (Ehrlein and Haas-Deppe 1998Citation ). Even with iso-osmotic enteral diets comprised of polymeric macronutrients, osmolality rapidly increases in the intestinal lumen because of the pancreatic degradation of the substrates (Ehrlein and Haas-Deppe 1998Citation ). Therefore, the conditions of enteral feeding are completely different from those of rehydration solutions.

The effect on the absorption of water, sodium and macronutrients obtained with iso-osmotic glucose-electrolyte solutions cannot be applied to enteral diets. The sodium content of enteral diets may differ depending on patients' needs. First, sodium content must meet daily requirements. However, there is a wide range between the minimal (~40 mmol/d) and maximal requirement (~140 mmol/d) of sodium. With most enteral diets, the sodium concentration varies from 40 to 70 mmol sodium/L, providing a sufficient daily supply of sodium by the infusion of a 2-L solution.

Second, sodium concentration might influence the transepithelial net flux of sodium and water. A previous study in humans (Spiller et al. 1987Citation ) showed that sodium absorption is directly proportional to the sodium concentrations of enteral diets. Concentrations <90 mmol sodium/L resulted in a net sodium and water secretion. Due to this result, the authors (Spiller et al. 1987Citation ) recommended enteral diets containing a high sodium concentration of >=90 mmol/L, especially in patients with massive intestinal resection where sodium and water losses may be life threatening. However, that study was performed with diluted, isotonic diets. With diets of high energy density, the increasing osmolality in the intestinal lumen because of the rapid degradation of the macronutrients will modulate the net flux of both sodium and water (Ehrlein and Stockmann 1998Citation ). In response to a hypertonic meal, monosaccharides and amino acids induce net sodium, chloride and water secretion (Chang and Rao 1994Citation ). Therefore, the experimental procedure of Spiller et al. (1987)Citation did not correspond to that of regular enteral feeding.

Third, the sodium content of the diet may also influence the absorption of glucose, amino acids and peptides. The uptake of glucose from gut lumen into enterocytes is driven by the sodium electrochemical potential gradient across the brush border membrane (Wright et al. 1994Citation ). The kinetics of the SGLT-1 transporter clearly illustrate the sodium dependence of the glucose transport (Wright et al. 1994Citation ). Additionally, several in vivo studies (Annegers 1964Citation , Csáky 1963Citation , Csáky and Zollicofer 1960Citation , Ortiz et al. 1979Citation , Schultz and Curran 1970Citation ) showed that removal of sodium from the lumen by substituting sodium with lithium, potassium, mannitol or Tris markedly reduced or completely inhibited active sugar and amino acid absorption.

In contrast, some studies in humans (Fleshler et al. 1966,Citation Olsen and Ingelfinger 1968,Citation Saltzman et al. 1972Citation ) found the sodium concentration of solutions had only small effects on the absorption of glucose and amino acids. A reduction of intraluminal sodium concentration from 140 to 2.5 mmol/L diminished glucose absorption by <20% (Saltzman et al. 1972Citation ). The authors supposed that the perfusion of a short segment (30 cm) with high perfusion rates (16 mL/min) might cause poor mixing and allow a microclimate of high sodium concentrations adjacent to the brush border membrane, even when luminal sodium concentration was small (Saltzman et al. 1972Citation ). In all previous studies, isotonic nutrient-electrolyte solutions were used. It remains to be determined whether the sodium concentration of enteral diets characterized by high energy density and consequently high osmolality influences absorption of glucose, amino acids and peptides. An increase in sodium concentration of enteral formulas inevitably increases the osmolality of the diet.

However, the interrelationships between the sodium concentration of the diet, the absorption of macronutrients and net fluxes of sodium and water are complex. An increase in sodium concentrations may influence the absorption of carbohydrates and proteins. The absorption of these macronutrients is associated with a reduction in intraluminal osmolality. There are further bidirectional fluxes of sodium and water depending on both osmotic forces and sero-mucosal differences in sodium concentrations. Due to these multifactorial interactions, the effects of increasing sodium concentration cannot be predicted by theoretical considerations, but have to be evaluated experimentally.

Therefore, the aim of the present study was to clarify the effects of the sodium concentration of enteral diets on the absorption of macronutrients and the net fluxes of sodium and water. These parameters were measured by perfusing a 150-cm jejunal segment with enteral diets of various sodium concentrations in unanesthetized miniature pigs. Because we expected that changes in sodium concentration would influence osmolality and that the major effect of sodium concentrations might be caused by osmotic effects, we used three nutrient solutions that differed in the degree of hydrolysis of the macronutrients and, consequently, in osmolality. The sodium concentration of the solutions was varied between 30 and 150 mmol/L.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Studies were performed in five female "Troll" miniature pigs (Medical Service Munich, Germany) weighing 44–50 kg. The animals were fed twice a day with a diet containing 75% of energy as carbohydrates, 15% as proteins, and 10% as fat. The energy supply was 7 MJ/d, corresponding to 400 kJ/kg 0.75. The diet was supplemented with fiber (Bran Buds, Kellogg, Bremen, Germany) and a mixture of vitamins and eclectrolytes.

Surgical procedures.

The procedures used in this study were approved by the Animal Care Committee of the Regierungspräsidium, Stuttgart, Germany. Surgical procedures were performed under general anesthesia. After intramuscular application of 5 mg tiletamine and zolazepam/kg (1:1) (TILEST, Parke-Davis, Berlin, Germany), anesthesia was maintained by halothane on O2-N2O. Three cannulas made of silicone rubber (Elastosil R401/70E, Wacker, Munich, Germany) were implanted into the proximal jejunum 100, 200 and 365 cm distal to the ligament of Treitz (Fig. 1). The cannulas were exteriorized through the right abdominal wall. The intraluminal base of the cannulas were positioned at the abdominal wall in a ventrodorsal direction.



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Figure 1. Positioning of the cannulas in the proximal jejunum of miniature pigs and perfusing a 150-cm jejeunal test segment with nutrient solutions. A balloon catheter used for infusion was inserted through the middle cannula. It was continuously inflated at constant pressure. The residues of the perfusion solution were drained from the distal cannula. The proximal cannula was used to drain the chyme of a test meal.

 
Measurement of nutrient absorption and transepithelial net flux of sodium and water.

The jejunal segment located between the middle and the distal cannulas was perfused with enteral diets. The residues of the infused enteral diets were drained by the distal cannula, whereas the chyme emptying from the stomach, bile and pancreatic secretion were drained by the proximal cannula. Absorption of macronutrients and transepithelial net flux of sodium and water were measured by the differences between infused and recovered macronutrients or water according to the equation described by Modigliani et al. (1973)Citation :

All diets were supplemented with the non-absorbable marker cobalt-EDTA (50 mg/L) (Udén et al. 1980Citation ).

Enteral diets.

Three enteral diets were used: a commercial oligopeptide diet, an oligomeric diet, and a polymeric diet5. The commercial diet Peptisorb(Pfrimmer, Erlangen, Germany) contained 75% of energy as carbohydrates 15% as proteins and 10% as fat (Table 1).We prepared the oligomeric and polymeric diets ourselves. The ratio of carbohydrates, protein and fat was adapted to that of the commercial diet Peptisorb. The commercial diet originally had an energy density of 4.2 MJ/L (1 Mcal/L). The energy density was reduced to 3.4 MJ/L to allow us to add sodium and a solution of cobalt-EDTA as a nonabsorbable marker. The energy density of the oligomeric and polymeric diets was also adjusted to 3.4 MJ/L (0.8 Mcal/L) so that all three diets had the same energy density. The commercial oligopeptide diet was infused into the jejunal segment without pancreatic enzymes because carbohydrates and proteins the substrates responsible for osmolality, were already hydrolyzed. The compositions of macronutrients and of electrolytes are summarized in Table 1 .


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Table 1. Compositions of commercial diet Peptisorb, oligomeric and polymeric diets1

 
The carbohydrate component of the oligomeric diet consisted of maltodextrin (C-Pur 1934, Cerestar, Krefeld, Germany). It was composed of 1.5% glucose, 35% maltose, 21% maltotriose and 42.5% oligosaccharides. The protein component consisted of hydrolyzed whey protein (Hyprol 8080, Quest International, Zwijndrecht, The Netherlands). It was composed of 15% amino acids, 50% di- and tripeptides, 30% oligopeptides and 5% polypeptides. A commercial emulsion of triglycerides (Lipovenös 10%, Fresenius, Bad Homburg, Germany) was used as the fat component. One day before the oligomeric diet was prepared, the fat component was hydrolyzed in vitro by pancreatic enzymes as described previously (Weber and Ehrlein 1998Citation ). Compared to the commercial oligopeptide diets the macronutrients of the homemade oligomeric diet were hydrolyzed to a larger extent. Consequently, the osmolality of the homemade oligomeric diet was much higher (Table 2). Preliminary experiments showed that the concomitant infusion of pancreatic enzymes did not enhance the absorption rate of energy from the oligomeric diet, i.e., no further luminal degradation of macronutrients by pancreatic enzymes was required and final hydrolysis by the brush border enzymes was sufficient to provide optimal absorption rates of the three macronutrients. Therefore, the oligomeric diet was infused without supplemental pancreatic enzymes. The enzymes used for fat hydrolysis had already lost their activity.


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Table 2. Osmolality of Peptisorb, oligomeric, and polymeric diets1

 
The polymeric diet was composed of soluble starch (C-Pur 1905, Cerestar, Krefeld), lactalbumin and an emulsion of triglycerides (Lipovenös 10%, Fresenius, Bad Homburg, Germany) (Table 1) . Because bile and pancreatic juice were lacking in the jejunal study segment, bile was added to the polymeric diet, and a solution of pancreatic enzymes was infused concomitantly with the polymeric diet. The bile was produced by dissolving 15 g bile extract (B-8631, Sigma, St. Louis, MO) in 100 mL distilled water. The bile solution (1.82 g) was added to 100 mL of the polymeric diet providing micellar formation. The pancreatic solution consisted of 3.33 g Pancreatin(P-1750, Sigma, St. Louis, MO) dissolved in 100 mL distilled water. The polymeric diet and the pancreatic solution were infused into the jejunum by separate pumps (KP 2000, Desaga, Heidelberg, Germany) so that hydrolysis of the macronutrients commenced in the small intestine. Pancreatic solution (0.5 mL ) was added to 2.0 mL of the diet, resulting in a concentration of 4.4 g Pancreatin/L solution. Preliminary experiments showed that this concentration of pancreatic enzymes provided hydrolysis of the major part of the macronutrients within 5–6 min (Ehrlein and Stockmann 1998Citation ).

NaCl was to the oligomeric diet added to achieve concentrations of 30, 60, 90, 120 and 150 mmol sodium/L. A concentration of 30 mmol sodium/L could not be prepared for the polymeric and the oligopeptide diets because the sodium content of the polymeric substrates and of the commercial diet was too large. Therefore, the sodium concentrations of the polymeric diet and the oligopeptide diet was adjusted to 60, 90, 120 and 150 mmol/L. The concentrations of the other electrolytes are summarized in Table 1 .

In the present study we did not try to differentiate between the direct effects of sodium and the effects of osmolality by means of control experiments with mannitol because such controls are problematic. The osmolality of the intestinal contents may be different when sodium or mannitol are used as osmotic substrates; sodium can be absorbed as well as secreted, and consequently osmolality and fluxes of water will depend on sodium fluxes. This does not occur with mannitol. Therefore, the osmotic effects of mannitol as control might be completely different from those of sodium and thus might be misleading.

Experimental procedure.

At the onset of each experiment, the cannulas were opened, and a balloon catheter was inserted into the middle cannula (Fig. 1) . The tip of the catheter was positioned 15 cm aboral of the cannula. Thus the length of the jejunal test segment was 150 cm. The balloon was continuously inflated with air by a pump at a constant pressure of 25 cm of water to occlude the intestinal lumen (Fig. 1) . The corresponding volume of the balloon varied between 5 and 15 mL, resulting in a balloon diameter between 10 and 20 mm. One of the enteral diets was infused into the jejunal segment via the balloon catheter over a period of 90 min. The residues of diets remaining unabsorbed were drained from the distal cannula. The ventro-dorsal direction of the cannulas and the upward flow of digesta facilitated the outflow of chyme and the residues of the diets through the opened cannulas (Fig. 1) .The initial 30 min of the 90-min perfusion period served as an equilibration period. During the subsequent 60-min test period, absorption rates of macronutrients and energy and transepithelial sodium and water fluxes were measured. The infusion rate of all diets into the jejunal segment was 2.5 mL/min, including infusion of pancreatic enzymes with the polymeric diet. The oligomeric diet and the commercial diet Peptisorb were infused without pancreatic enzymes, whereas the polymeric diet was supplemeted with pancreatic enzymes. Because the energy density was 3.4 MJ/L (0.8 Mcal/L), the energy supply was 8.4 kJ/min (2 kcal/min). This energy load corresponded to the postprandial energy flow in these miniature pigs. At the end of the test period, infusion of the diet was stopped, and saline was perfused over an additional 30 min for marker recovery. The mean recoveries of the cobalt marker during the 60-min test period and the complete experiment were 98.1 ± 5.9 % and 96.0 ± 5.8 %, respectively. At the middle of the test period, transit time was measured by injection of an 0.5-mL bolus (5 mg) chromium-EDTA into the jejunal segment. During the subsequent period, the effluent of the distal cannula was collected in intervals of 0.5–2 min for recovery of the transit marker.

At the onset of the test period, the animals were fed a test meal to induce postprandial conditions. The meal was eaten within 2 min. The energy of the meal (3485 kJ) met one-half of the daily requirement. The meal was drained by the proximal cannula as it emptied from the stomach. Consequently, bile and pancreatic juice did not enter the jejunal test segment during the experiment.

Analysis of macronutrients, energy, marker, sodium and water.

The concentrations of macronutrients (carbohydrates, proteins and fat), sodium concentration, water content and the cobalt marker were determined in the diets and the effluent of the distal cannula. The methods of analysis have been previously described in detail (Weber and Ehrlein 1998Citation ).

The concentration of carbohydrates was determined enzymatically (starch-test, Boehringer, Mannheim, Germany). The protein content was determined by an automatic nitrogen analyser (Macro-N, Heraeus, Hanau, Germany). The fat was extracted with petroleum ether and determined gravimetrically as described previously (Ehrlein and Stockmann 1998Citation ). The energy densities of the diets and of the intestinal effluents were determined as the sum of the energy of each nutrient. The energy values used to convert g macronutrients (kJ) are summarized in (Table 3).


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Table 3. Energy values used to convert the amounts of nutrients from g to kJ1

 
The concentrations of sodium, cobalt and chromium were measured by atomic absorption spectrometry (Perkin Elmer, Überlingen, Germany) (Farah and Sneddon 1993Citation ). The water content of the diets and the samples was measured by the difference in weight between the liquid and freeze-dried material.

Transit time and flow rate.

The mean transit time of a bolus was determined as the time interval between the injection of the chromium-EDTA marker and the recovery of 50% of the marker in the effluent of the distal cannula. The flow rate (mL/min) was defined as the volume of fluid passing the jejunal segment per min. It was determined from the equation:

where volume effluent is the volume/minrecovered at the distal cannula, marker infused and marker recovered are the amounts of marker that were infused and recovered, respectively, during the 60-min test period.

In vitro hydrolysis of the polymeric diets.

The polymeric diets were concomitantly infused with pancreatic enzymes to induce hydrolysis of the macronutrients in the jejunal segment. The degradation of carbohydrates and proteins increases the osmolality. To estimate the increase in osmolality occurring in the gut, the polymeric diets were hydrolyzed in vitro by pancreatic enzymes. As in the in vivo experiments, 5 mL of a 3.33% Pancreatin solution was added to 20 mL of the diets. The solution was kept at 37oC. Over a 30-min period samples were taken in 1-min intervals, and the osmolality was immediately measured by an osmometer (OM 801, Vogel, Giessen, Germany). Osmolality rapidly increased within a few minutes. After this initial period, osmolality increased only slightly approaching plateau values. The osmolality occurring in the gut because of the hydrolysis might depend on the transit time. Therefore, the osmolality of the in vitro hydrolysis was evaluated after a period corresponding to the mean transit time (5.6 min) of the polymeric diets (Table 2) . These values might resemble the osmolalities occurring in the jejunal segment after hydrolysis of the polymeric macronutrients.

Statistics.

With each diet and each sodium concentration two experiments were performed in each pig, i.e., with each pig 26 experiments were carried out. One experiment was performed per day. The sequence of the diets was randomly selected. Data from the five pigs are presented as grand means ± SD calculated from the mean values of the two experiments in each pig. Relationships between sodium concentrations and absorption of macronutrients and energy, fluxes of water and sodium, sodium concentration of chyme, flow rate and transit time were tested with linear regression analysis. When no linear regression existed, differences of the parameters among the diets were tested using ANOVA and the Student-Newman-Keul's test. A probability value P < 0.05 was considered significant.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Absorption rates of macronutrients and energy.

With all three enteral diets, increasing concentrations of sodium did not significantly influence absorption rates of the three macronutrients and of energy (Fig. 2).Regression analysis showed no linear relationships between sodium concentrations and the absorption rates of carbohydrates, proteins, fat or total energy. Variance analysis also showed no significant differences of the absorption rates among the different sodium concentrations. Therefore, the mean absorption rates of carbohydrates, proteins, fat and total energy were determined for each diet (Table 4) .The mean absorption rates for energy and protein were significantly smaller with the oligopeptide diet Peptisorb when compared to the oligomeric diet (Table 4) , whereas the mean absorption rates of the three macronutrients and total energy were not significantly different between the oligomeric and polymeric diets and between the polymeric diet and the oligopeptide diet Peptisorb.



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Figure 2. Absorption of carbohydrate, protein, fat and total energy with the oligomeric diet (top panel), polymeric diet (middle panel) and the oligopeptide diet Peptisorb (bottom panel). Stacked columns represent mean values of carbohydrate, protein and fat absorption of the 5 miniature pigs; the whole column indicated by black lines and error bars show mean energy absorption + SD, n = 5 miniatur pigs. Both regression and variance analyses showed that absorption rates were not significantly changed by increasing sodium concentrations of the diets.

 

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Table 4. Absorption rates of energy, carbohydrate, protein and fat during perfusion of jejunal test segment of miniature pigs with three enteral diets1

 
Net flux of water, flow rate and transit time.

The perfusion of all three diets was associated with net secretion of water caused by the high osmolality of the solutions. With increasing sodium concentrations, net secretion of water increased linearly with all three diets (Fig. 3 , top paneland Table 5 ). With the oligomeric, polymeric and oligopeptide diets, an increase in sodium concentration by 30 mmol/L enhanced the net secretion of water by 0.37, 0.26 and 0.32 mL/min, respectively (Table 5) .Both the differences in water secretion among the three diets and the linear increase in water secretion with increasing sodium concentration were caused by the osmolality of the solutions (Fig. 4, top panel).The osmolality of Peptisorb was less than that of the oligomeric diet and the polymeric diet after hydrolysis by pancreatic enzymes. With the oligomeric, polymeric and oligopeptide diets, an increase in osmolality by 100 mosmol/kg enhanced net secretion of water by 0.6, 0.5 and 0.6 mL/min, respectively (Table 5) .



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Figure 3. Relationships between sodium concentrations of diets and secretion of water (top panel) and flow rate (bottom panel). Values are means ± SD, n = 5 miniature pigs. With all diets, secretion of water and flow rate increased linearly as sodium concentration increased. Parameters of linear regression are summarized in Table 5 .

 

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Table 5. Parameters of linear regressions between sodium concentration of diets, water secretion, flow rate, osmolality of diets and sodium secretion in miniature pigs1

 


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Figure 4. Relationshsips between osmolality of diets and secretion of water (top panel) and flow rate (bottom panel). Values are means ± SD, n = 5 miniature pigs. For all diets, secretion of water and flow rate increased linearly as osmolality of diets increased. Osmolality of Peptisorb was significantly smaller in comparison with the oligomeric and polymeric diets. Osmolality of polymeric diet was measured in vitro after hydrolysis with pancreatic enzymes. Parameters of linear regression are summarized in Table 5 .

 
All diets were infused at 2.5 mL/min. The flow rate at the distal end of the jejunal segment depended on the sodium concentration of the diets (Fig. 3 , bottom panel). Because the sodium concentration influenced the osmolality of diets, and osmolality influenced water secretion (Fig. 4 , top panel), there were also close linear ralationships between the osmolality of diets and flow rates (Fig. 4 , bottom panel) and between the net secretion of water and flow rates (Fig. 5).An increase in water secretion by 1 mL/min also enhanced the flow rate by 1mL/min (Table 5) . Because of the enhanced osmolality of the diets, the maximal flow rate was about twice that of the infusion rate (Fig. 5) .



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Figure 5. Flow rate of chyme was closely correlated with net flux of water. Points represent values of 3 diets and 4 sodium concentrations in 5 miniature pigs. Parameters of linear regression are summarized in Table 5 .

 
In contrast to the flow rate, the transit time of a bolus marker was not influenced by the sodium concentration of the diets or by the concomitant secretion of water. However, the transit time differed among the diets. With the oligomeric and polymeric diets the transit time was significantly shorter than with the oligopeptide diet Peptisorb (P < 0.05). The mean transit times were 5.4 ± 0.28, 5.6 ± 0.43 and 6.7 ± 0.29 min, respectively.

Net flux of sodium and intestinal sodium concentrations.

With the three diets and with all sodium concentrations varying between 30 and 150 mmol/L, a net flux of sodium into the intestinal lumen occurred. We had expected that, with increasing sodium concentrations of the diets, the secretion of sodium would be diminished because of the reduced gradient between plasma and the intestinal lumen. However, although a slight reduction in sodium secretion with increasing concentration occurred, there was no significant correlation between the sodium concentration and the sodium secretion. With the oligomeric diet, sodium secretion was significantly greater (P < 0.05) than the polymeric diet and the oligopeptide diet Peptisorb (Fig. 6, left panel).There was a positive, linear relationship between secretion of water and secretion of sodium (Fig. 7). This indicated that net secretion of sodium was influenced by secretion of water.



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Figure 6. Net secretion of sodium and intestinal sodium concentrations with the 3 diets. With the oligomeric diet, mean secretion of sodium was significantly (P < 0.05) larger in comparison with the polymeric diet and Peptisorb (left panel). The intestinal sodium concentration was significantly (P < 0.05) larger with Peptisorb in comparison with the polymeric diet and the oligomeric diet (right panel). Values are means ± SD, n = 5 miniature pigs. a, b, c indicate significant differences.

 


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Figure 7. Linear relationship between net flux of water and sodium secretion. Points represent values of 3 diets and 4 sodium concentrations in 5 miniature pigs. Parameters of linear regression are summarized in Table 5 .

 
The sodium concentration of the intestinal effluent did not increase as the sodium concentrations of the diets increased. Because of the concomitant secretion of both sodium and water, the sodium concentration of the chyme reached ~100 mmol/L with the oligomeric and polymeric diets and 125 mmol/L with the oligopeptide diet Peptisorb (P < 0.05; Fig. 6 , right panel).


    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The major findings of the present study were as follows: 1) increasing sodium concentrations of the diets were associated with increasing osmolality of the solutions resulting in a linear increase in net secretion of water and flow rate of chyme. 2) With all diets, net secretion of sodium occurred. The sodium secretion was independent of the initial sodium concentration of the diets. It was linearly correlated with net flux of water and was largest with the hyperosmotic oligomeric diet. 3) The sodium concentration of the effluent did not correspond to the initial sodium concentration of the diets. 4) The absorption of macronutrients and of total energy was independent of the initial sodium concentration of the diets.

The results on the relationships between sodium concentrations of enteral diets and net secretion of sodium and water differed markedly from that of a previous study (Spiller et al. 1987Citation ). Spiller et al. (1987)Citation observed a significant linear decrease in net secretion of sodium and water as sodium concentration of the diets increased, whereas in our study the net secretion of sodium was independent of the initial sodium concentration of the diets, and the net secretion of water increased linearly with increasing sodium concentrations. The differences are obviously caused by the different experimental designs. In Spiller's study (1987), the enteral diets were diluted to obtain isotonic solutions. However, in enteral nutrition, diets of high energy density are required to meet the daily energy supply without surplus of water. The energy density of commercial enteral diets varies between 4.184 and 5.23 MJ/L (1000 and 1250 kcal/L) (Gottschlich et al. 1997Citation ). The initial osmolality of enteral diets depends on the degradation of carbohydrates and proteins. Polymeric diets are iso-osmotic, whereas oligomeric diets are hyperosmotic. The commercial enteral diets usually represent a compromise between the degree of degradation of carbohydrates and proteins and the increase in osmolality. Thus, the commercial diet Peptisorb was only slightly hyperosmotic. However, the consequence of the incomplete degradation of carbohydrates and proteins is that, without further hydrolysis by pancreatic enzymes, the absorption of the macronutrients is limited. In the present study, significantly less total energy was absorbed from the commercial diet Peptisorb than from the oligomeric diet. On the other hand, the low initial osmolality of oligopeptide or polymeric diets is only an apparent advantage. The present results showed that, in the small intestine, the polymeric macronutrients were rapidly hydrolyzed by pancreatic enzymes providing absorption rates similar to those with oligomeric macronutrients, but osmolality increased rapidly reaching values comparable with those of the oligomeric diet. Consequently, enteric application of diets with high energy density is inevitably associated with a pronounced increase in osmolality. This effect markedly influences water and sodium fluxes. Therefore, results obtained with diluted enteral diets or nutrient solutions of low energy density are not representative for enteric feeding. In the present study, the net secretion of water was the most pronounced phenomenon. Because of the increasing osmolality of the diets with increasing sodium concentrations, the net secretion of water increased linearly. There is evidence that luminal macronutrients and hypertonic chyme modulate the paracellular permeability. Changes in cytoskeletal arrangement of the perijunctional actomyosin ring can increase the permeability of the tight junctions (Blada 1991,Citation Chang and Rao 1994,Citation Madara and Trier 1994Citation ). This effect of macronutrients and osmolality may not only enhance absorption of water parallel with the absorption of macronutrients, but may also enhance serosal-mucosal fluxes of sodium and water. In the present study, net secretion of water increased the luminal volume and flow rate and diluted the chyme. The linear relationship between net water and net sodium fluxes indicated that the reduction in sodium concentration by dilution obviously increased the sodium gradient between the plasma and intestinal contents and enhanced sodium secretion. Consequently, the net secretion of sodium was not diminished as the sodium concentration of the diet increased. For enteral nutrition, our recommendations, derived from the present findings, are contrary to that of Spiller et al. (1987)Citation . According to our results the sodium concentration of enteral diets should be as low as possible and only just meet the patient's minimal daily requirement of sodium. The lower the sodium concentration the lower the osmolality and consequently net secretion of water and sodium. In contrast, Spiller et al. (1987)Citation recommended a high sodium concentration of >=90 mmol/L, especially in jejunostomy patients with massive resection of the distal small intestine where losses of sodium and water may be life threatening. However, in such patients enteral diets might be infused into the stomach rather than into the small intestine because of the osmotic problems.

The sodium concentration of the effluent did not increase with increasing sodium concentrations of the diets. With the oligomeric and polymeric diets the sodium concentrations of the jejunal contents was ~100 mmol/l, whereas the oligopeptide diet Peptisorb was 125 mmol/l. In the present study we did not determine bidirectional fluxes of sodium and water, but measured only their net fluxes. It is likely that under the present experimental conditions both serosal-mucosal (secretion) and mucosal-serosal (absorption) fluxes of water and sodium occurred. Secretion of water was primarily caused by osmolality and secretion of sodium by the sodium gradient. On the other hand, the absorption of glucose, amino acids and peptides is associated with the osmotic absorption of water. Additionally, the co-transport of sodium with glucose and amino acids and the Na+/H+exchange transport in association with the absorption of amino acids and peptides (Chang and Rao 1994,Citation Gerson. 1971,Citation Loike et al. 1996,Citation Loo et al. 1996Citation ) may have produced absorption of sodium and water. Therefore, the sodium concentration of the chyme was the result of the bidirectional fluxes of both sodium and water. Because the absorption of macronutrients was significantly smaller with the commercial diet Peptisorb compared to the oligomeric diet, the absorption of sodium and water might also have been smaller. This effect might have contributed to the higher sodium concentration of the jejunal contents with Peptisorb.

Discrepancies exist in the literature about the effects of the sodium concentration of solutions on absorption of glucose, amino acids and peptides. In vitro studies clearly showed that the absorption of glucose, amino acids, and peptides depends on the sodium concentration of the solution (Holtug and Skadhauge 1991,Citation Schultz and Curran 1970Citation ). Under in vitro conditions, the sodium concentration can be exactly defined on both sites of the epithelium, and undesirable serosal-mucosal fluxes can be eliminated. In contrast, during in vivo perfusion of an intestinal segment with electrolyte-glucose or amino acid solutions, sodium may enter the gut lumen across paracellular pathways. In the proximal small intestine, permeability of the paracellular junctions is larger than in the distal small intestine (Chadwick et al. 1977,Citation Loehry et al. 1973,Citation Madara and Trier 1994,Citation Madara et al. 1980Citation ). Therefore, with in vivo studies the sodium effects may be different between specific regions of the gut. Sodium fluxes may further depend on a variety of experimental conditions, such as concentrations of macronutrients influencing paracellular permeability (Chang and Rao 1994,Citation Madara and Trier 1994Citation ) or concentrations of sodium being responsible for the gradient between plasma and luminal contents. In all previous studies on interactions between sodium concentrations and solute absorption isotonic solutions were used. The present study is the first that investigated the effects of the sodium concentrations of diets with high energy density and, consequently, high osmolality on the absorption of macronutrients and energy. With all three diets and all sodium concentrations a net secretion of sodium occurred. Therefore, in all cases the sodium concentrations were sufficient to provide optimal absorption rates of macronutrients, even with initial low sodium concentrations of the diets. The increase in sodium concentration had no stimulatory effect on solute absorption. These findings indicate that, under the conditions of enteric feeding, absorption of macronutrients is independent of the sodium concentration of the diet. Therefore, sodium concentrations of diets can be minimized without negative effects on nutrient absorption.


    ACKNOWLEDGMENTS
 
The authors thank Ingeborg Ehrlein and Margrit Hartmann for technical assistance. We thank the companies for providing enteral diets and silicone elastomer for the preparation of cannulas.


    FOOTNOTES
 
1 To whom correspondence should be addressed. Back

1 Supported by the Deutsche Forschungsgemeinschaft, grant EH 64/6–4. Back

2 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked ''advertisement'' in accordance with 18 USC section 1734 solely to indicate this fact. Back

3 Abbreviation used: SGLT, Sodium dependent glucose transporter Back

4 Terminology used: The polymeric dietcontained the three macronutrients in large molecular form.The hyperosmotic oligomeric diet contained the three macronutrients as hydrolyzed substrates not requiring further pancreatic degradation. The commercial formula containing oligopeptides and oligosaccharides was defined as oligopeptide diet. Back

Manuscript received June 16, 1998. Initial review completed August 18, 1998. Revision accepted November 4, 1998.


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