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Experimental Models for the Investigation of Water and Solute Transport in Man

Implications for Oral Rehydration Solutions

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Summary

For patients suffering from mild to moderate dehydration, oral rehydration therapy has proved a simple and efficacious treatment. There remains, however, a need to develop improved oral rehydration solutions (ORS), and suitable experimental models are required to develop and assess new formulations. The ideal model for such investigations would take into account rates of gastric emptying, influx and efflux of water and solutes in the intestine, and the consequent changes in body composition. As no such definitive model is currently available, a variety of techniques are used to examine parts of the process of intestinal absorption.

Clinical studies which assess the recovery of dehydrated patients during therapy using different ORS will ultimately evaluate the efficacy of treatment. However, ethical considerations, the relative insensitivity of this technique and the exacting nature of such studies make this approach unsuitable for the development of specific ORS. Gastric emptying of solutions can be determined by a variety of techniques, among which the radioactive tracer method offers the advantage of having no direct effect on the emptying rate, giving almost continuous measurement and allowing the use of relatively small volumes of fluids. Perfusion techniques allow measurement of the net flux of water and solute in predetermined sections of the intact human intestine. Measurement of the rate of accumulation in the circulation of orally ingested tracer molecules for water and solutes can estimate unidirectional flux. This method allows for the rates of gastric emptying and intestinal absorption of the test substance, but the rate of efflux of the tracer from the vascular space must be known to calculate net uptake.

Each of these models has limitations, and care must be taken in interpreting the results in a clinical context. However, their use in the development of improved formulations is well established.

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References

  • Alam AN, Sarker SA, Molla AM, Rahaman MM, Greenough WB. Hydrolysed wheat based oral rehydration solution for acute diarrhoea. Archives of Disease in Childhood 62: 440–444, 1987

    Article  PubMed  CAS  Google Scholar 

  • Aperia A, Marin L, Zetterstrom R, Gunoz H, Neyzi O, et al. Salt and water homeostasis during oral rehydration therapy. Journal of Pediatrics 103: 364–369, 1983

    Article  PubMed  CAS  Google Scholar 

  • Brener W, Hendrix TR, McHugh PR. Regulation of the gastric emptying of glucose. Gastroenterology 85: 76–82, 1983

    PubMed  CAS  Google Scholar 

  • Burks TF, Galligan JJ, Porreca F, Barber WD. Regulation of gastric emptying. Federation Proceedings 44: 2897–2901, 1985

    PubMed  CAS  Google Scholar 

  • Camilleri M, Malagelada JR, Brown ML, Becker G, Zinsmeister AR. Relation between antral motility and gastric emptying of solids and liquids in humans. American Journal of Physiology 249: G580–G585, 1985

    PubMed  CAS  Google Scholar 

  • Clements ML, Levine MM, Cleaves F, Hughes TP, Caceres M, et al. Comparison of simple sugar/salt versus glucose/electrolyte oral rehydration solutions in infant diarrhoea. Journal of Tropical Medicine and Hygiene 84: 189–194, 1981

    PubMed  CAS  Google Scholar 

  • Consolazio CF, Johnson RE, Pecora LG. The computation of metabolic balances. In Physiological measurements of metabolic functions in man, pp. 313–339, McGraw-Hill, New York, 1963

    Google Scholar 

  • Cooper H, Levitan R, Fordtran JS, Ingelfinger FJ. A method for studying absorption of water and solute from the human small intestine. Gastroenterology 50: 1–7, 1966

    PubMed  CAS  Google Scholar 

  • Cunha Ferreira RMC, Elliott EJ, Walker-Smith JA, Farthing MJG. Glycine and glucose polymer (ORS): efficacy in an animal model of secretory diarrhoea. Gut 27 (Suppl. 1): A1245, 1986

    Google Scholar 

  • Cunha Ferreira RMC, Elliott EJ, Brennan EA, Walker-Smith JA, Farthing MJG. Has glycine anything to offer oral rehydration therapy? Gastroenterology 92: 1359, 1987

    Google Scholar 

  • Darrow DC, Pratt EL, Flett J, Gamble AH, Wiese HF. Disturbances of water and electrolytes in infantile diarrhoea. Paediatrics 3: 129–156, 1949

    CAS  Google Scholar 

  • Davis JM, Lamb DR, Burgess WA, Bartoli WP. Accumulation of deuterium oxide in body fluids after ingestion of D2O-labelled beverages. Journal of Applied Physiology 63: 2060–2066, 1987

    PubMed  CAS  Google Scholar 

  • Edelman IS. Exchange of water between blood and tissues. Characteristics of deuterium oxide equilibration in body water. American Journal of Physiology 171: 279–296, 1952

    PubMed  CAS  Google Scholar 

  • Elliott EJ, Walker-Smith JA, Farthing MJG. The role of bicarbonate and base precursors in treatment of acute gastroenteritis. Archives of Disease in Childhood 62: 91–95, 1987

    Article  PubMed  CAS  Google Scholar 

  • Fagundes-Neto U, Viaro T, Lifshitz F. Tolerance to glucose polymers in malnourished infants with diarrhoea and disaccharide intolerance. American Journal of Clinical Nutrition 41: 228–234, 1985

    PubMed  CAS  Google Scholar 

  • Finberg L. Oral glucose-electrolyte solutions. American Journal of Diseases of Children 139: 552, 1985

    PubMed  CAS  Google Scholar 

  • Fordtran JS, Locklear TW. Ionic constituents and osmolality of gastric and small intestinal fluids after eating. American Journal of Digestive Diseases 11: 503–521, 1966

    Article  PubMed  CAS  Google Scholar 

  • Fordtran JS, Levitan R, Bikerman V, Burrows BA, Ingelfinger FJ. The kinetics of water absorption in the human intestine. Transactions of the Association of American Physicians 74: 195–206. 1961

    PubMed  CAS  Google Scholar 

  • French AB, Brown IF, Good CJ, McLeod GM. Comparison of phenol red and polyethylene glycol as nonabsorbable markers for the study of intestinal absorption in humans. American Journal of Digestive Diseases 13: 558–564, 1968

    Article  PubMed  CAS  Google Scholar 

  • George JD. New clinical method for measuring the rate of gastric emptying: the double sampling test method. Gut 9: 237–242, 1968

    Article  PubMed  CAS  Google Scholar 

  • Gray GM, Ingelfinger FJ. Intestinal absorption of sucrose in man: interrelation of hydrolysis and monosaccharide product absorption. Journal of Clinical Investigation 45: 388–398, 1966

    Article  PubMed  CAS  Google Scholar 

  • Halliday D, Rennie MJ. The use of stable isotopes for diagnosis and clinical research. Clinical Science 63: 485–496, 1982

    PubMed  CAS  Google Scholar 

  • Heese HdeV, Tonin C, Bowie MD, Evans A. The management of metabolic acidosis in acute gastro-enteritis. British Medical Journal 2: 144–146, 1966

    Article  PubMed  Google Scholar 

  • Holdsworth CD. Absorption of protein, amino acids and peptides — a review. In Burland WL, Samuel PD (Eds) Transport across the intestine, pp. 14–34, Churchill Livingstone, Edinburgh, 1972

    Google Scholar 

  • Holt S, Cervantes J, Wilkinson AA, Wallace JHK. Measurement of gastric emptying rate in humans by real-time ultrasound. Gastroenterology 90: 918–923, 1986

    PubMed  CAS  Google Scholar 

  • Hunt JN, Knox MT. Regulation of gastric emptying. In Code CF, Heidel W (Eds) Handbook of physiology, section 6, alimentary canal, vol. IV, pp. 1917–1935, American Physiology Society, Washington, 1968

    Google Scholar 

  • Hunt JN, Pathak JD. The osmotic effects of some simple molecules and ions on gastric emptying. Journal of Physiology 154: 254–269, 1960

    PubMed  CAS  Google Scholar 

  • Hunt JN, Spurrell WR. The pattern of emptying of the human stomach. Journal of Physiology 113: 157–168, 1951

    PubMed  CAS  Google Scholar 

  • Hunt JN, Stubbs DF. The volume and energy control of meals as determinants of gastric emptying. Journal of Physiology 245: 209–225, 1975

    PubMed  CAS  Google Scholar 

  • Hunt JN, Smith JL, Jiang CL. Effect of meal volume and energy density on the gastric emptying rate of carbohydrates. Gastroenterology 89: 1326–1330, 1985

    PubMed  CAS  Google Scholar 

  • Hunt JB, Elliott EJ, Fairclough PD, Farthing MJG. Effects of [Na] on water and Na absorption from hypotonic oral rehydration solutions. Clinical Science 74 (Suppl. 18): abstract no. 5, 2, 1988

  • Islam MR, Greenough WB, Rahaman MM, Choudhury AK, Sack DA. Labon-gur (common salt and brown sugar) oral rehydration solution in the treatment of diarrhoea in adults. Journal of Tropical Medicine and Hygiene 83: 41–45, 1980

    PubMed  CAS  Google Scholar 

  • Islam MR, Samadi AR, Ahmed SM, Bardhan PK, Ali A. Oral rehydration therapy: efficacy of sodium citrate equal to sodium bicarbonate for correction of acidosis in diarrhoea. Gut 25: 900–904, 1984

    Article  PubMed  CAS  Google Scholar 

  • Jodal M, Lundgren O. Countercurrent mechanisms in the mammalian gastrointestinal tract. Gastroenterology 91: 225–241, 1986

    PubMed  CAS  Google Scholar 

  • Jones BJM, Brown BE, Loran JS, Edgerton D, Kennedy JF, et al. Glucose absorption from starch hydrolysates in the human jejunum. Gut 24: 1152–1160, 1983

    Article  PubMed  CAS  Google Scholar 

  • Jones BJM, Higgins BE, Silk DBA. Glucose absorption from maltotriose and glucose oligomers in the human jejunum. Clinical Science 72: 409–414, 1987

    PubMed  CAS  Google Scholar 

  • Kjellman B, Ronge E. Oral solutions for gastroenteritis — optimal glucose concentrations. Archives of Disease of Childhood 57: 313–315, 1982

    Article  CAS  Google Scholar 

  • Leiper JB. Absorption of water and electrolytes from hypotonic, isotonic and hypertonic solutions. Proceedings of the Nutrition Society 45: abstract no. 78A, 1986

  • Leiper JB, Maughan RJ. The effect of luminal tonicity on water absorption from a segment of the intact human jejunum. Journal of Physiology 378: abstract no. 95P, 1986

  • Leiper JB, Maughan RJ. A perfusion technique giving improved reproducibility in measurement of jejunal absorption in man. Clinical Science 73 (Suppl. 17): abstract no. 168, 46, 1987

  • Leiper JB, Maughan RJ. The effect of bicarbonate or base precursor on water and solute absorption for a glucose-electrolyte solution in the human jejunum. Digestion 41: 39–45, 1988

    Article  PubMed  CAS  Google Scholar 

  • Leiper JB, Watt SJ, Maughan RJ. Effect of glucose and glycine mixtures on water absorption from a segment of the intact human intestine. Clinical Science 72 (Suppl. 16): abstract no. 255, 89, 1987

    Google Scholar 

  • Leiper JB, Fallick AE, Maughan RJ. Comparison of water absorption from an ingested glucose electrolyte solution (GES) and potable water using a tracer technique in healthy volunteers. Clinical Science 74 (Suppl. 18): abstract no. 257, 68, 1988a

  • Leiper JB, Maughan RJ, Davidson J, Gemmell HG, Smith FW. Evaluation of a scintigraphic technique for measurement of gastric emptying of liquid from healthy volunteers. Clinical Science 74 (Suppl. 18): abstract no. 81, 22, 1988b

  • Leiper JB, Maughan RJ, Miller JDB, Murray RJ. Enteral versus intravenous fluid and electrolyte replacement after elective cholecystectomy. Clinical Nutrition 7: 101–104, 1988c

    Article  Google Scholar 

  • Levitt MD. Use of the constant perfusion technique in the non steady state. Gastroenterology 73: 1450–1454, 1977

    PubMed  CAS  Google Scholar 

  • Lifshitz F, Wapnir RA. Oral hydration solutions: experimental optimization of water and sodium absorption. Journal of Paediatrics 106: 383–389, 1985

    Article  CAS  Google Scholar 

  • Listernick R, Zieserl E, Davis AT. Oral glucose-electrolyte solutions as maintenance therapy of acute diarrhea. American Journal of Diseases of Children 139: 571–574, 1985

    PubMed  CAS  Google Scholar 

  • Love AHG, Phillips RA, Rohde JE, Veall N. Sodium-ion movement across the intestinal mucosa in cholera patients. Lancet 2: 151–153, 1972

    Article  PubMed  CAS  Google Scholar 

  • Love AHG, Rohde JE, Abrams ME, Veall N. The measurement of bidirectional sodium fluxes across the intestinal wall in man using whole-gut perfusion. Clinical Science 44: 267–278, 1973

    PubMed  CAS  Google Scholar 

  • McClelland GR, Sutton JA. Epigastric impedance: a non-invasive method for the assessment of gastric emptying motility. Gut 26: 607–614, 1985

    Article  PubMed  CAS  Google Scholar 

  • Maffei HVL, Nobrega FJ. Gastric pH and microflora of normal and diarrhoeic infants. Gut 16: 719–726, 1975

    Article  PubMed  CAS  Google Scholar 

  • Malmud LS, Fisher RS, Knight LC, Rock E. Scintigraphic evaluation of gastric emptying. Seminars in Nuclear Medicine 12: 116–125, 1982

    Article  PubMed  CAS  Google Scholar 

  • Marin L, Saner G, Sokucu H, Gunoz H, Neyzi O, et al. Oral rehydration therapy in neonates and young infants with infectious diarrhoea. Acta Paediatrica Scandinavica 76: 431–437, 1987

    Article  PubMed  CAS  Google Scholar 

  • Meeroff JC, Go VLW, Phillips SF. Osmotic control of gastric emptying: perfusion studies in the human duodenum. Gastroenterology 66: abstract no. 89, 743, 1974

    Google Scholar 

  • Meeroff JC, Screiber DS, Trier JS, Blacklow NR. Abnormal gastric motor function in viral gastroenteritis. Annals of Internal Medicine 92: 370–372, 1980

    PubMed  CAS  Google Scholar 

  • Meeuwisse GW. High sugar worse than high sodium in oral rehydration solutions. Acta Paediatrica Scandinavica 72: 161–166, 1983

    Article  PubMed  CAS  Google Scholar 

  • Minami H, McCallum EW. The physiology and pathophysiology of gastric emptying in humans. Gastroenterology 86: 1592–1610, 1984

    PubMed  CAS  Google Scholar 

  • Modigliani R, Bernier JJ. Absorption of glucose, sodium and water by the human jejunum studied by intestinal perfusion with a proximal occluding balloon and at variable flow rates. Gut 12: 184–193, 1971

    Article  PubMed  CAS  Google Scholar 

  • Nichols BL, Soriano HA. A critique of oral therapy of dehydration due to diarrheal syndromes. American Journal of Clinical Nutrition 30: 1457–1472, 1977

    PubMed  CAS  Google Scholar 

  • Orenstein SR. Enterai versus parenteral therapy for intractable diarrhea of infancy: a prospective, randomized trial. Journal of Pediatrics 109: 277–286, 1986

    Article  PubMed  CAS  Google Scholar 

  • Parsons DS. Methods for investigation of intestinal absorption. In Code CF, Heidel W (Eds) Handbook of physiology, section 6, alimentary canal, vol. III, pp. 1177–1216, American Physiology Society, Washington, 1968

    Google Scholar 

  • Patra FC, Mahalanabis D, Jalan KN, Sen A, Banerjee P. Can acetate replace bicarbonate in oral rehydration solution for infantile diarrhoea? Archives of Disease in Childhood 57: 625–627, 1982a

    Article  PubMed  CAS  Google Scholar 

  • Patra FC, Mahalanabis D, Jalan KN, Sen A, Banerjee P. Is oral rice electrolyte solution superior to glucose electrolyte solution in infantile diarrhoea? Archives of Disease in Childhood 57: 910–912, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Patra FC, Mahalanabis D, Jalan KN, Sen A, Banerjee P. In search of a super solution: controlled trial of glycine-glucose oral rehydration solution in infantile diarrhoea. Acta Paediatrica Scandinavica 73: 18–21, 1984

    Article  PubMed  CAS  Google Scholar 

  • Phillips SF, Summerskill WHJ. Water and electrolyte transport during maintenance of isotonicity in human jejunum and ileum. Journal of Laboratory and Clinical Medicine 70: 686–698, 1967

    PubMed  CAS  Google Scholar 

  • Pinson EA. Water exchanges and barriers as studied by the use of hydrogen isotopes. Physiological Reviews 32: 123–134, 1952

    PubMed  CAS  Google Scholar 

  • Ramakrishna BS, Mathan VI. Water and electrolyte absorption by the colon in tropical sprue. Gut 23: 843–846, 1982

    Article  PubMed  CAS  Google Scholar 

  • Read NW, Al Janabi MN, Bates JE, Barber DC. Effect of oral gastrointestinal intubation on the passage of a solid meal through the stomach and small intestine in humans. Gastroenterology 84: 1568–1572, 1983

    PubMed  CAS  Google Scholar 

  • Reitemeier RJ, Code CF, Orvis AL. Comparison of rate of absorption of labelled sodium and water from the upper small intestine of healthy human beings. Journal of Applied Physiology 10: 256–260, 1957

    PubMed  CAS  Google Scholar 

  • Rolston DDK, Moriarty KJ, Farthing MJG, Kelly MJ, Clark ML, et al. Acetate and citrate stimulates water and sodium absorption in the human jejunum. Digestion 34: 101–104, 1986

    Article  PubMed  Google Scholar 

  • Ruppin H, Bar-Meir S, Soergel KH, Wood CM, Schmitt MG. Absorption of short-chain fatty acids by the colon. Gastroenterology 78: 1500–1507, 1980

    PubMed  CAS  Google Scholar 

  • Sandhu BK, Jones BJM, Brook CGD, Silk DBA. Oral rehydration in acute infantile diarrhoea with a glucose-polymer electrolyte solution. Archives of Disease in Childhood 57: 152–160, 1982

    Article  PubMed  CAS  Google Scholar 

  • Santosham M, Burns BA, Reid R, Letson GW, Duncan B, et al. Glycine-based oral rehydration solution: reassessment of safety and efficacy. Journal of Pediatrics 109: 795–801, 1986

    Article  PubMed  CAS  Google Scholar 

  • Schedl HP. Use of polyethylene glycol and phenol red as unabsorbed indicators for intestinal absorption studies in man. Gut 7: 159–163, 1966

    Article  PubMed  CAS  Google Scholar 

  • Scholer JF, Code CF. Rate of absorption of water from stomach and small bowel of human beings. Gastroenterology 27: 565–577, 1954

    PubMed  CAS  Google Scholar 

  • Silk DBA. Diet formulation and choice of enterai diet. Gut 27 (Suppl. 1): 40–46, 1986

    Article  PubMed  CAS  Google Scholar 

  • Silk DBA, Webb JPW, Une AE, Clark ML, Dawson AM. Functional differentiation of human jejunum and ileum: a comparison of the handling of glucose, peptides, and amino acids. Gut 15: 444–449, 1974

    Article  PubMed  CAS  Google Scholar 

  • Sladen GEG. A review of water and electrolyte transport. In Burland WL, Samuel PD (Eds) Transport across the intestine, pp. 14–34, Churchill Livingstone, Edinburgh, 1972

    Google Scholar 

  • Sladen GEG. Methods of studying intestinal absorption in man. In McColl I, Sladen GEG (Eds) Intestinal absorption in man, pp. 1–49, Academic Press, London, 1975

    Google Scholar 

  • Sladen GEG, Dawson AM. Further studies on the perfusion method for measuring intestinal absorption in man: the effects of a proximal occlusive balloon and a mixing segment. Gut 11: 947–954, 1970

    Article  PubMed  CAS  Google Scholar 

  • Tothill P, McLoughlin GP, Heading RC. Techniques and errors in scintigraphic measurement of gastric emptying. Journal of Nuclear Medicine 19: 256–261, 1978

    PubMed  CAS  Google Scholar 

  • Visscher MB, Fletcher ES, Carr CW, Gregor HP, Bushey MS, et al. Isotopic tracer studies on the movement of water and ions between intestinal lumen and blood. American Journal of Physiology 142: 550–575, 1944

    CAS  Google Scholar 

  • Wapnir RA, Lifshitz F. Osmolality and solute concentration — their relationship with oral rehydration solution effectiveness: an experimental assessment. Pediatric Research 19: 894–898, 1985

    Article  PubMed  CAS  Google Scholar 

  • Whalen GE, Harris JA, Geenen JE, Soergel KH. Sodium and water absorption from the human small intestine. Gastroenterology 51: 975–984, 1966

    PubMed  CAS  Google Scholar 

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  1. Department of Environmental and Occupational Medicine, University Medical School, Foresterhill, Aberdeen, AB9 2ZD, UK

    J. B. Leiper &  R. J. Maughan

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Leiper, J.B., Maughan, R.J. Experimental Models for the Investigation of Water and Solute Transport in Man. Drugs 36 (Suppl 4), 65–79 (1988). https://doi.org/10.2165/00003495-198800364-00010

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