Influence of meal composition on canine jejunal water and electrolyte absorption.

The absorption of water and electrolytes from the proximal jejunal lumen increases immediately after a meal. This meal-induced jejunal absorption occurs in jejunal segments out of normal gastrointestinal continuity. This study was designed to characterize the jejunal absorptive response to a series of isovolumetric gavage-delivered stimuli. Twenty-five-centimeter canine proximal jejunal Thiry-Vella fistulas were constructed, and jejunal absorption studies (n = 66) were performed by luminal perfusion of the jejunal segments with an isotonic buffer containing 14C-labeled polyethylene glycol. Each study consisted of a 1-hour basal period, followed by a 3-hour experimental period. Nine groups were studied, each receiving one of the following isovolumetric stimuli delivered via the gavage route: water, 0.9% saline, mixed meal, protein, lipid, carbohydrate, and mannitol (150 mmol/L, 300 mmol/L, and 600 mmol/L). The water and 0.9% saline gavage groups showed no significant changes in integrated postprandial water and electrolyte absorption above basal. The isocaloric mixed meal, protein, lipid, carbohydrate, and mannitol groups all had significantly increased integrated postprandial jejunal water and electrolyte absorption above basal (P less than 0.05). These results indicate that a proabsorptive signal for meal-induced jejunal absorption originates from or distal to the stomach. Meal-induced jejunal absorption occurs in response to nutrients of diverse composition and is also responsive to nonnutritive solutes such as mannitol. These findings support a new role for gastric or intestinal chemo- or osmo-receptors in stimulating the neurohumoral mechanisms that mediate meal-induced jejunal absorption.     

Luminal dopamine modulates canine ileal water and electrolyte transport

Previous studies have suggested that dopamine stimulates active ileal ion absorption via ₂-adrenergic or dopaminergic receptor activation. Identification of a dopamine 1a receptor on rat enterocytes located in intestinal crypts prompted this investigation of the effect of luminally administered dopamine on water and ion transport in the canine ileum. Absorption studies (n=27) were performed in dogs with 25-cm ileal Thiry-Vella fistulas. Perfusion with [¹⁴C PEG was used to calculate absorption of water and electrolytes from the Thiry-Vella fistula. Experiments consisted of three 1-hr periods: basal, luminal drug infusion at 10^–4 M, and recovery. Agonists used included dopamine (DOP: -adrenergic, D₁ and D₂ receptor) and SKF 38393 (D₁ receptor). Antagonists used included terazosin (TZ: ₁) and yohimbine (YOH: ₂). DOP caused significant increases in water and electrolyte absorption. TZ and YOH prevented the dopamine-induced proabsorptive response. Luminal DOP may serve as a proabsorptive modulator of ileal transport, acting via ₁, ₂, and dopaminergic receptors. The development of more potent proabsorptive dopamine analogs, which maintain the ability to broadly activate mucosal receptors, may be useful in such clinical situations as diabetic diarrhea, short gut syndrome, or following small bowel transplantation.Presented in part as a poster presentation at the Annual Meeting of the American Gastroenterological Association, New Orleans, May 14–18, 1994, and published in abstract form inGastroenterology 106:A432, 1994.Supported in part by National Institutes of Health grant R29-DK 41178 (C.J.Y.).     

Central nervous system influence of prostaglandin E2 on jejunal water and electrolyte transport in conscious dogs

The effects of intracerebroventricular (i.c.v.) vs. i.v. administration of prostaglandin E2 (PGE2) on net fluxes of water, Na+, and K+ through a jejunal Thiry-Vella loop were investigated before or after previous treatment with adrenergic blockers, indomethacin, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB8) in conscious dogs. Administered intracerebroventricularly at doses of 20-100 ng/kg, PGE2 significantly reduced (p less than 0.01), in a dose-related manner, the net fluxes of water, Na+, and K+, which were reversed from an absorption to a secretion. Intravenously administered PGE2 at a five times higher dosage failed to significantly alter net water and electrolyte fluxes. Phentolamine (0.2 mg/kg body wt) and tolazoline (2 mg/kg body wt) administered intravenously abolished the secretory effects of centrally administered PGE2 (50 ng/kg). However, 10 times lower dosages of phentolamine and tolazoline administered intracerebroventricularly did not prevent the PGE2-induced secretion of water and electrolytes. Intracerebroventricular administration of indomethacin (10 micrograms/kg body wt) and TMB8 (1 microgram/kg body wt), did not modify the effect of i.c.v.-administered PGE2; however, indomethacin administered intracerebroventricularly alone stimulated water and electrolyte absorption. None of these treatments results in a significant (p greater than 0.05) change in mean transit time through the Thiry-Vella loop. We conclude that centrally administered PGE2 influences jejunal water, Na+, and K+ absorption, through a mechanism related to adrenergic innervation and/or involving at least alpha 2-adrenoceptors. The results also suggest that PGE2 in the central nervous system controls jejunal water and ion transport in the dog.     

Effect of a model of canine jejunoileal orthotopic autotransplantation on jejunal and ileal transport of water and electrolytes

Canine jejunoileal transplantation induces an early profuse watery diarrhea of uncertain etiology. Our aim was to determine the temporal effects of a canine model of jejunoileal autotransplantation (a model devoid of confounding effects of ischemia-reperfusion or immune rejection) on basal jejunal and ileal absorption of water and electrolytes to determine if impaired absorption is responsible for the diarrhea. Our hypothesis was that net absorption of water and electrolytes in an enterically isolated loop would decrease after jejunoileal transplantation. Four groups of dogs (N 6) were prepared with 80-cm modified Thiry-Vella loops: group I, neurally intact jejunum; group II, autotransplanted jejunum; group III, neurally intact ileum; and group IV, autotransplanted ileum. The loops were perfused for 3 hr with 150 mM NaCl at 3 ml/min under fasted conditions; transit time through the loop was determined by bolus of a nonabsorbable marker. Dogs were studied on three separate days at one, two, eight, and nine weeks postoperatively. Net absorptive fluxes of water and electrolytes and transit times were similar (P>0.05) between neurally intact and autotransplant groups (group I vs II and group III vs IV) at each time point. Ileal loops absorbed more than jejunal loops, and transit was slower in ileal loops (eachP<0.05). Our findings suggest that, despite the obligate disruption of extrinsic innervation, enteric (intrinsic) neural continuity, and lymphatic drainage that accompanies this canine model of jejunoileal autotransplantation, net basal absorptive function of water and electrolytes during the fasted state was not decreased nor was transit altered either in jejunum or ileum. These findings have important implications for clinical small intestinal transplantation in man.Supported by NIH RO1 DK39337 (M.G.S.), Ethicon Corporation, and Mayo Foundation.     

Microvillus inclusion disease. In vitro jejunal electrolyte transport

Microvillus inclusion disease is an inherited intestinal brush border membrane defect that causes severe fluid and electrolyte malabsorption. In an infant with microvillus inclusion disease (confirmed by electron microscopic evaluation of rectal, jejunal, and gallbladder mucosae), basal stool output was massive (greater than 125 mL . kg-1 . day-1) and was not altered by treatment with clonidine or octreotide. A proximal jejunostomy with mucous fistula was placed, allowing separation of proximal from distal tract outputs (60 mL . kg-1 . day-1 and 100 mL . kg-1 . day-1, respectively). A 10-cm jejunal segment was excised during surgery and mounted in Ussing chambers for determination of transepithelial Na+ and Cl fluxes. Compared with intestine of normal infants, this infant's epithelium showed transmural conductance and unidirectional ion fluxes that were only 30% of normal. With respect to both Na+ and Cl, the excised jejunum was in a net secretory state. Theophylline (5 mmol/L) increased net Cl secretion slightly. In response to mucosal D-glucose (30 mmol/L), jejunal mucosal-to-serosal Na+ flux doubled. In the infant, glucose-electrolyte solution administered intrajejunally did not significantly change stool output, suggesting that all of the solution (40 mL/kg) was absorbed. Subtotal enterocolectomy, in theory, could have decreased purging by 66% in this infant with microvillus inclusion disease, but diarrhea would still have been significant.     

Effects of intravenous calcitonin on water, electrolyte, and calcium movement across in vivo rabbit jejunum and ileum.

The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport.     

Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects.

The effect of sulphasalazine and olsalazine on jejunal and ileal water and electrolyte absorption was investigated in normal subjects by a steady state intestinal perfusion of a physiological glucose bicarbonate electrolyte solution in the absence and presence of increasing concentrations of each drug. (Olsalazine 0.25 g/l, 1.0 g/l, jejunum; 0.5 g/l, 1.0 g/l, ileum; sulphasalazine 0.25 g/l, 0.5 g/l, 2.0 g/l jejunum; 1.0 g/l, 2.0 g/l, ileum.) In the jejunum olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride, and potassium absorption (p less than 0.05). In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03). In the jejunum sulphasalazine had a dose related and significant inhibitory effect on water, bicarbonate, and sodium absorption and at 2.0 g/l an inhibitory effect on chloride, potassium (p less than 0.005), and glucose (p less than 0.05) absorption. In the ileum sulphasalazine had no significant effect on water and electrolyte absorption. All inhibitory effects were rapidly reversible. These data show that unexplained diarrhoea in patients with ulcerative colitis treated with olsalazine may occur as a consequence of inhibition of water and electrolyte absorption in the small intestine and that the mechanisms of inhibition of sulphasalazine and olsalazine are different.     

Increased canine jejunal absorption of water,glucose, and sodium with intestinal pacing

Our aim was to determine if pacing a segment of jejunum backwards with electrical stimuli could increase absorption from it. In four dogs, 75-cm loops of jejunum were isolated from the intestinal stream. After recovery, fluid was infused into the proximal stoma of the loop and effluent collected from the distal stoma for three consecutive 30-min periods. In the second period electrical stimuli were applied to the distal end of the loop to drive the pacesetter potentials of the loop, hence its contractions, backwards. The output of water, glucose, and sodium from the loop was decreased, and the transit of content through the loop was slowed during backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli enhances absorption of water, glucose, and sodium from that segment.An abstract of this work has been published in Surgical Forum 28:428–430, 1977.Research support: USPHS Grants AM 18278, AM 6908; and Wellcome Foundation.     

Alterations in carrier-mediated glutamine transport after a model of canine jejunal autotransplantation

The effects of small bowel transplantation (SBTx) on absorptive function are unknown. Preliminary experiments showed a decrease in absorption of glutamine. Our aim was to determine mechanisms of decreased ileal transport of glutamine utilizing a model of intestinal autotransplantation. Seven dogs were studied before and after a model of jejunoileal autotransplantation.In vivo absorption experiments were performed before and two and eight weeks postoperatively with an electrolyte solution containing glutamine (20 mM).In vitro glutamine transport was studied using brush-border membrane vesicles (BBMV) prepared from ileal mucosa obtained from six other dogs and compared to a controls.In vivo net absorptive flux of glutamine decreased at two weeks but returned toward baseline by eight weeks (P=0.06). Transport of glutamine into BBMVs was decreased at two weeks and remained decreased at eight weeks. , a measure of carrier affinity was unchanged but , a function of the number of transporter was decreased at two and eight weeks. Glucose transport was unchanged. It is concluded that jejunoileal autotransplantation decreases ileal absorption of glutamine by a decrease in carrier-mediated transport of glutamine.Supported in part by NIH DK39337 (M.G.S.), NIH CA45327 (W.W.S.), and the Mayo Foundation.Presented at the Society of Surgery of the Alimentary Tract, May 1995, in San Diego, California. An abstract of this work was published inGastroenterology 108:A1235, 1995.     

Jejunal water and electrolyte transport in human cryptosporidiosis

Cryptosporidiosis may have severe clinical consequences in both immunocompromised and immunocompetent individuals. However, pathophysiological mechanisms that are responsible for diarrhea are poorly understood. We performed jejunal perfusion studies in patients with human immunodeficiency virus-related cryptosporidial diarrhea to measure water and electrolyte transportin vivo. Five patients with human immunodeficiency virus-related cryptosporidiosis and nine healthy volunteers were studied using a triple-lumen steady-state jejunal perfusion technique. Stool volume measurement and distal duodenal biopsy showed that the patients had diarrhea (600–1500 ml/24 hr) and morphological abnormalities of small intestinal mucosa. Net water, sodium, and chloride movement in the jejunum was not significantly different from healthy controls. In these patients with watery diarrhea and morphological mucosal abnormalities, we found no evidence that cryptosporidial diarrhea was due to a secretory state in the proximal small intestine. We conclude that diarrhea may be due to secretion of electrolytes and water efflux more distally or to other abnormalities of gastrointestinal function.This work was supported by the Smith and Nephew Foundation.     

Effect of taurine conjugated bile salts with and without lecithin on water and electrolyte transport in the canine gallbladder in vivo.

Because dihydroxy bile salts alter water and electrolyte transport in the intestine, we tested the effects of taurine conjugated bile salts on water and electrolyte transport in the canine gallbladder in vivo. 16.7 mM taurodeoxycholate or taurochenodeoxycholate completely abolished net absorption of water (P less than 0.01). 40 mM taurocholate significantly reduced net water absorption (P less than 0.05), whereas 16.7 mM taurocholate had no significant effect. Net movement of electrolytes was closely related to net water movement. Water and electrolyte absorption continued undisturbed when the gallbladders were exposed to 16.7 mM taurodeoxycholate together with 5.6 mM lecithin. Biliary lecithin, therefore, is important for the protection of the mucosa of the gallbladder from the potentially damaging effects of bile salts.     

Effects of enteral infusion of hypertonic saline and nutrients on canine jejunal motor patterns

The aim of the study was to clarify the effects of hypertonic solutions on jejunal motility. The study focused on differential effects of hypertonic saline and nutrients. Motility of the canine proximal jejunum was recorded with closely spaced strain-gauge transducers. During fasting, hyperosmotic solutions (up to 1520 mosmol/liter) of saline or nutrients (1 kcal/ml) were infused into the proximal jejunum (0.5–1.5 ml/min) up to 6 hr. The hyperosmotic solutions stimulated jejunal motility. With both increasing osmolarity of saline or increasing energy load of nutrients, jejunal motility linearly declined. The reduction of motility was associated with a change in motor pattern from a propulsive to a more segmenting one. Hypertonic glucose evoked a significantly smaller level of motor activity compared with both saline (at given osmolarities) and an elemental diet (at given energy loads). Motility parameters were not different between glucose and maltose, although osmolarity of maltose was less than half (760 vs 1520 mosmol/liter). In contrast, a mixture of glucose-fructose exerted a smaller inhibition of jejunal motility than glucose. The hypertonic solutions of saline or nutrients were tolerated over 2 hr; with hypertonic saline retrograde power contractions with or without vomiting occurred, whereas with hypertonic nutrients vomiting was preceded by strong inhibition of jejunal motility. Three conclusions can be derived from the present results: (1) The behavior of jejunal motility suggested that the motor activity was the result of both a local stimulation and an inhibitory feedback mechanism. (2) The different degree of inhibition between glucose and saline indicated that the nutrient itself played a major role in the inhibitory feedback regulation, whereas osmolarity was of minor importance. (3) Comparisons between different nutrients suggested a linkage between inhibitory control of motility and the absorptive capacity of the gut for the single nutrient.     

降钙素基因相关肽对犬冠脉流量及冠状动脉的作用

本研究通过整体及离体灌流实验观察到重庆冠脉狭窄时，犬冠脉流量（ＣＢＦ），平均动脉压（ＭＡＰ）明显减小，而心率（ＨＲ）则增加。狭窄３０ｍｉｎ后由冠状动脉注射降钙素基因相关肽（ＣＧＲＰ）０．３μｇ／ｋｇ后，ＣＢＦ、ＭＡＰ和ＨＲ可恢复正常水平。同时，缺血犬的离体冠状动脉对ＣＧＲＰ的反应也出现改变。大冠脉舒张反应明显降低，而小冠脉的舒张反应与正常相比，无明显改变，这可能与缺血后大冠脉的内皮细胞容易损伤有关。同时也提示:急性心肌缺血时，冠脉流量的减少，主要由于小冠状动脉收缩所致。     

Effect of lithium ingestion on water and electrolyte transport in rat intestine

The effect of lithium ingestion on intestinal electrolyte and water transport was studied in adult Sprague-Dawley rats. We fed animals a lithium-supplemented diet for 1, 2, 4, or 16 wk before in vivo perfusion of the jejunum and colon. Lithium feeding did not alter jejunal transport of water, electrolytes, or glucose, However, at 4 and 16 wk (16-wk data given) the colon increased net water (168%), sodium (160%), and chloride (140%) absorptions, and the transmural potential difference (396%) as compared with control animals. In addition, the colon absorbed both bicarbonate and potassium against an unfavorable electrochemical gradient. The increased colonic sodium absorption was not associated with an increase in mucosal Na+, K+-ATPase activity. Furthermore, in lithium-fed animals deoxycorticosterone acetate stimulated mucosal Na+, K+-ATPase activity, but it did not further increase net sodium absorption. Neither jejunal nor colonic electrolyte transport was affected 24 h after being gavage-fed lithium. These results suggest that chronic lithium ingestion has a unique mechanism of action as other means of chronically increasing sodium absorption are associated with increased mucosal Na+, K+-ATPase activity.