Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum.

Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor l-N(G)-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.

Site of action of morphine sulfate and motilin in the induction of "premature" phase III-like activity in the canine gastrointestinal tract.

Our aims were twofold: First, to determine whether motilin and morphine induce "premature" Phase III-like motor activity by acting on receptors located in the wall of the proximal duodenum; second, to characterize the relationship between onset of pharmacologically induced Phase III-like activity and changes in plasma motilin concentration. Five dogs were studied with use of motilin, in doses ranging from 0.01 to 0.8 micrograms/kg, and with use of morphine sulfate, in doses ranging from 2.5 to 80 micrograms/kg, administered by close intra-arterial injection to the proximal duodenum at 40% of the spontaneous migrating motor complex cycle. The minimum effective doses of motilin and morphine necessary to induce premature Phase III-like activity when given intravenously were also determined. Both motilin and morphine induced premature Phase III-like activity in the duodenum, the characteristics of which were similar to those of spontaneous Phase III except that the velocity of migration in morphine-induced Phase III-like activity was greater. The minimum effective dose of each agent was no different whether given intra-arterially or intravenously. The latencies of response to intra-arterial and intravenous administration of each agent were no different. Doses of morphine effective in inducing premature Phase III-like activity led to increases in plasma motilin concentration that occurred only after Phase III-like activity had begun in the duodenum. Our results suggest that humoral initiation of fasting motor activity in the duodenum by motilin and morphine does not occur by stimulation of receptors located within the wall of the duodenum.

Chronic extrinsic denervation after small bowel transplantation in rat jejunum: Effects and adaptation in nitrergic and non-nitrergic neuromuscular inhibitory mechanisms.

BACKGROUND: Extrinsic denervation of the transplanted small bowel could play a substantial role in motor dysfunction of the transplanted gut. We attempted to determine the effect of chronic extrinsic denervation on intestinal contractility. METHODS: Jejunal longitudinal muscle strips were obtained from rats 1 week and 8 weeks after (1) syngeneic small bowel transplantation, (2) ischemia/reperfusion, or (3) gut transection/reanastomosis. Nonoperated rats (naive controls) and sham-operated rats (sham controls), 1 week after celiotomy/gut manipulation, served as controls. We evaluated the effects of exogenous nitric oxide, increasing doses of cholinergic and adrenergic agonists, and electrical field stimulation (EFS) in the presence or absence of N(G)-monomethyl-l-arginine, methylene blue, tetraethylammonium, or tetrodotoxin. RESULTS: Spontaneous contractile activity (_chi +/- SEM), when compared with the naive controls (11.3 +/- 2.0 g.5 min/mg), was increased in all 4 groups at 1 week (15.9 +/- 10 to 19.4 +/- 2 g.5 min/mg; P < or =.03 each) but not at 8 weeks postoperatively. The inhibition of contractile activity by nitric oxide was increased in small bowel transplantation in naive controls at 8 weeks to 80% +/- 10% versus 50% +/- 7% (P <.02). EFS induced an inhibition of contractile activity that was tetraethylammonium- and tetrodotoxin-sensitive but N(G)-monomethyl-l-arginine- and methylene blue-insensitive; the maximal EFS-induced inhibition was increased at 1 week and 8 weeks but only in the small bowel transplantation groups to 103% +/- 5% and 95% +/- 7%, respectively, versus 72% +/- 8% in naive controls (P

In situ neural isolation of the entire canine upper gut: effects on fasting and fed motility patterns.

BACKGROUND: Multiorgan upper gut transplantation is becoming clinically feasible; however, the effects of multivisceral transplantations on gastrointestinal motility are unknown. Our aim was to determine the neural and hormonal mechanisms controlling motility patterns after complete extrinsic denervation of the upper gut as a model of multivisceral upper gut autotransplantation. METHODS: Seven dogs successfully underwent in situ neural isolation of the stomach, entire small intestine, proximal colon, liver, and pancreas by transecting all connections (distal esophagus, midcolon, all nerves, lymphatics) to this multivisceral complex except the celiac artery, superior mesenteric artery, and the suprahepatic and infrahepatic vena cava; these vessels were meticulously stripped of adventitia under optical magnification. Blood flow was not disrupted to prevent confounding effects of ischemia-reperfusion injury. After 1- to 2-week recovery, myoelectric and manometric recordings of stomach and myoelectric recordings of small bowel were obtained from conscious animals. RESULTS: During fasting the characteristic cycling migrating motor complex (MMC) was observed in the stomach and small intestine. The gastric component of the MMC was absent in one of the seven dogs. Regular cycling of the MMC during fasting, however, was intermittently disrupted and replaced by a noncyclic pattern of intermittent contractions in two of seven dogs 43% of the recording time. A small meal (50 gm liver) did not abolish the MMC as occurs in normal dogs; in contrast, a large meal (500 gm liver) did abolish the MMC. CONCLUSIONS: Extrinsic innervation to the upper gut modulates but is not requisite for interdigestive and postprandial motility of the stomach. Because relatively normal global motility patterns are preserved, multivisceral upper gut transplantation should be a viable option in selected patients.

Mechanism mediating nitric oxide-induced inhibition in human jejunal longitudinal smooth muscle.

BACKGROUND: Enteric neurotransmission is a complex process involving multiple neurotransmitters, including nitric oxide (NO). Our aim was to evaluate the role and mechanism(s) of action of NO in normal human jejunal longitudinal smooth muscle. METHODS: Transmural strips of normal human jejunum obtained from subjects undergoing gastric bypass were studied in organ chambers. Effects of exogenous NO (7 x 10(-6) mol/L to 7 x 10(-5) mol/L) and electrical field stimulation (nonspecific release of endogenous neurotransmitters) on spontaneous contractile activity and on precontracted muscle strips (substance P, 10(-5) mol/L) were evaluated in the presence and absence of the competitive NO synthase inhibitor N(G)-amino-L-arginine (L-NNA, 10(-3) mol/L) and the specific soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazaolo-[4,3-a]-quinoxalin-1-one (ODQ, 10(-5) mol/L and 10(-4) mol/L). RESULTS: Exogenous NO dose-dependently inhibited spontaneous contractility and relaxed precontracted smooth muscle strips. The effects of NO were markedly attenuated or completely inhibited in the presence of ODQ. Electric field stimulation under nonadrenergic, noncholinergic conditions also inhibited spontaneous contractility and relaxed precontracted smooth muscle strips; both of these effects were attenuated, but not completely inhibited, in the presence of both ODQ and L-NNA. CONCLUSIONS: NO is an endogenous inhibitory neurotransmitter in human jejunal longitudinal smooth muscle, acting at least in part via a mechanism mediated by guanylyl cyclase. Other (non-nitrergic) nonadrenergic, noncholinergic inhibitory neurotransmitters are likely active in this portion of the human gut.

Role of extrinsic innervation in carbohydrate-induced ileal modulation of pancreatic secretion and upper gut function.

Previously we showed that carbohydrate (CHO) in the ileum slowed gastric emptying and increased pancreatic amylase secretion relative to that of other enzymes. Our aim here was to determine if extrinsic innervation of the jejunoileum participates in the CHO-induced ileal modulation of postprandial upper gut function. Six dogs were studied before and 2-3 weeks after in situ neural isolation of the jejunoileum (complete extrinsic denervation). Gastric emptying (GE) and pancreatic amylase secretion were quantitated for 4 h after a 300-ml meal containing 3H-PEH (liquid marker) and 99mTc sulfur colloid cooked with eggs (solid marker). Coincident with feeding, we started a distal ileal infusion of 150 mM NaCl or 40 mg.min-1 CHO. Extrinsic denervation abolished the slowing of GE of liquids and solids and the augmented increase in amylase and trypsin in relation to solid emptying seen in the neurally intact dogs prior to denervation. Denervation also abolished the decrease in total pancreatic exocrine secretion in response to ileal CHO. Increases in plasma concentrations of peptide YY (PYY) were correlated temporally with decreased GE of solids and increased exocrine secretion during ileal CHO in neurally intact dogs, but no increases in PYY release occurred after extrinsic denervation. Extrinsic denervation of the jejunoileum abolished the effect of ileal CHO on GE of liquids and solids, the decrease in total amylase secretion during ileal CHO, and the relative increase in enzyme secretion expressed as total enzyme output per percentage solid marker emptied. Extrinsic innervation of the jejunoileum mediates ileal modulation of GE and the relationship of amylase secretion to GE of solids. The mechanism of this effect may be via neurally mediated release of PYY.

Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats.

Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.

Nitric oxide pathways in circular muscle of the rat jejunum before and after small bowel transplantation.

Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.

Ileal absorptive adaptation to jejunal resection and extrinsic denervation: implications for living-related small bowel transplantation.

Net absorption of water, electrolytes, and simple nutrients decreases early after jejunoileal autotransplantation (extrinsic denervation) in a canine model but recovers toward normal by 8 weeks. However, the ability of the extrinsically denervated ileum to adapt after total jejunectomy, which would be relevant as a model of segmental small bowel transplantation, remains unknown. Two groups of five dogs each were studied before and 2 weeks and 12 weeks after 50% proximal enterectomy. A control group remained neurally intact, whereas the other group underwent extrinsic denervation (Ext Den) of the remaining ileum. Using a perfusion technique, net absorption of water, electrolytes, and five simple nutrients (glucose, arginine, glutamine, and oleic and taurocholic acids) was measured at the three time points. Ileal morphometry was also evaluated. All dogs developed diarrhea, which resolved by 12 weeks in all but two of the Ext Den dogs. Weight in both groups was decreased at 2 weeks (P <0.05), returned to normal at 12 weeks in control dogs, but remained low in Ext Den dogs (P <0.05). Maximal weight loss was greater in the Ext Den group (P <0.05). No consistent or important differences in net absorptive fluxes of water, electrolytes, or simple nutrients were noted either within or between groups at any time point. Villous height, crypt depth, and longitudinal muscle width increased significantly at 12 weeks after jejunectomy in the Ext Den dogs, but not in the control dogs (P <0.05). Extrinsic denervation of the ileum results in persistent weight loss after proximal 50% enterectomy. Despite diarrhea, only minor changes in electrolyte absorption occur, and ileal net absorption of simple nutrients remains unaffected. The ileum of extrinsically denervated dogs undergoes a more prominent morphometric adaptation after jejunectomy. Extrinsic denervation necessitated by small bowel transplantation, independent of immune effects, does not appear to suppress the ileal adaptive response to maintain net absorption of water, electrolytes, and simple nutrients.

Mechanisms of ileal adaptation for glucose absorption after proximal-based small bowel resection.

INTRODUCTION: The hexose transmembrane transporters SGLT1 and GLUT2 are present in low quantities in ileum where little glucose absorption occurs normally; however, glucose uptake in ileum is highly adaptable after small bowel resection. HYPOTHESIS: Ileal adaptability for glucose absorption after jejunal resection is mediated predominately by upregulation of GLUT2. METHODS: Rats underwent 70% proximal-based jejunoileal resection. Transporter-mediated glucose uptake was measured in proximal and distal remnant ileum 1 and 4 wk postoperatively (n = 6 rats, each) and in corresponding ileal segments in control and 1 wk sham laparotomy rats (n = 6, each) without and with selective inhibitors of SGLT1 and GLUT2. In separate groups of rats (n = 6, each), protein (Western blots), mRNA (reverse transcriptase polymerase chain reaction [RT-PCR]), and villus height (histomorphology) were measured. RESULTS: After 70% proximal intestinal resection, there was no dramatic change in protein or mRNA expression per cell of either SGLT1 or GLUT2, but median glucose uptake (nmol/cm/min) increased markedly from 52 (range 28-63) in controls to 118 (range 80-171) at 1 wk, and 203 (range 93-248) at 4 wk (p < or = 0.04 each) correlating with change in villus height (p < or = 0.03). CONCLUSIONS: Ileal adaptation for glucose transport occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of glucose transporters.

Early and long term effects of a model of intestinal autotransplantation on intestinal motor patterns.

The short and long term effects of a model of orthotopic jejunoileal autotransplantation on intestinal motility were studied in a model of four dogs that underwent autotransplantation of the entire jejunoileum. Serosal electrodes were placed to record intestinal motility patterns. Each dog was studied during fasting and after feeding early (two to six weeks) and late (14 to 17 weeks) after jejunoileal autotransplantation. During fasting, both the innervated duodenum and the autotransplanted jejunoileum showed the characteristic migrating motor complex (MMC) early after this model of transplantation, but the MMC in the two regions lacked temporal coordination. Late after transplantation, temporal reassociation of the MMC in the duodenum and jejunoileum occurred. Feeding a small meal (50 grams of liver) inhibited the MMC in the duodenum, but not in the jejunoileum either early or late after transplantation. These observations suggest that characteristic cyclic fasting motility patterns persist after this model of small intestinal transplantation and are dissociated temporally between innervated and transplanted regions for at least eight weeks, but then reassociate with time (greater than three months). Feeding a small meal did not induce a postprandial motor pattern in the transplanted region. The effects of these changes in motility on intestinal function remain unknown.

Jejunal and ileal absorptive function after a model of canine jejunoileal autotransplantation.

The effects of intestinal transplantation on the physiologic functions of the gut are not well understood. Our aim was to determine the effect of a large animal model of small intestinal transplantation (disruption of all neural and lymphatic continuity) on selected absorptive functions of the jejunoileum. Seven dogs were studied before and at 1, 4, and 12 weeks after a model of jejunoileal autotransplantation, which avoids confounding factors of immune rejection, immunosuppression, and harvest ischemia. Jejunal function was assessed by quantitative [3H]-folate and D-xylose absorption and ileal function by quantitative 57Co-vitamin B12 absorption. The role of lymphatic continuity was assessed by fecal fat recovery following 5 days of a controlled, high fat diet (75 g/day). All dogs developed a profuse, watery diarrhea that persisted for 6 to 12 weeks and lost about 15% body weight; however, absorption of D-xylose, folate, and vitamin B12 was unaffected at any time point. Fat absorption postoperatively was only mildly abnormal (less than or equal to 8 g/day) at all time points in five of seven dogs despite complete lymphatic disruption. We concluded that jejunoileal autotransplantation does not markedly affect these specific jejunoileal absorptive functions. Fat absorption in most dogs surprisingly remains almost normal. Anatomic and physiologic consequences of intestinal transplantation do not appear to induce global abnormalities in all absorptive functions in the nonrejecting jejunoileum.

A model of jejunoileal in vivo neural isolation of the entire jejunoileum: transplantation and the effects on intestinal motility.

The effects of intestinal transplantation on enteric physiology have not been well studied. Our aim was to determine the effect of jejunoileal transplantation on patterns of small intestinal motility. To avoid confounding effects of immune rejection or immunosuppression, we developed a model of autotransplantation in which all tissue connections to the entire jejunoileum were transected at the base of the mesentery except for the superior mesenteric artery and vein which were stripped meticulously of investing adventitia. After 3 weeks, motility was studied in eight dogs with intestinal electrodes during fasting, after meals of 50 and 500 g of liver, and during intravenous infusions of pentagastrin and cholecystokinin. During fasting, the characteristic inter-digestive migrating motor complex (MMC) was present in both the innervated duodenum and the "autotransplanted" jejunoileum; however, temporal coordination between the two regions was abolished. Feeding 50 g of liver abolished the MMC in the duodenum, but not in the jejunoileum; in contrast, 500 g of liver interrupted the MMC in both regions. Exogenous pentagastrin and cholecystokinin inhibited the MMC for the duration of the infusions. These findings suggest that extrinsic nerves and/or intrinsic (enteric) myoneural continuity do not initiate fasting motor patterns in the jejunoileum but do regulate the temporal coordination of motor patterns between segments of small intestine. Postprandial inhibition of the MMC is only in part mediated by neural factors. After transplantation, motility is abnormal; the overall effects on enteric physiology remain unknown.

Fate of oral neutralizing antacid and its effect on postprandial gastric secretion and emptying.

The fate and neutralizing efficiency of oral antacids (aluminum and magnesium hydroxides) as well as their effect on postprandial gastric function were quantified in 6 patients with duodenal ulcer disease. We employed a double-marker technique for measurement of gastric secretion and emptying and combined this with back-titration of the gastric samples and analysis of aluminum to trace the fate of antacid in the stomach and duodenum. These studies show that: (a) antacid therapy with aluminum and magnesium hydroxides significantly increases gastric secretion; (b) intragastric neutralization of gastric acid produces a significant and substantial decrease in net acid output (acid secreted minus acid neutralized), but the beneficial effects of neutralization are partially offset by incomplete intragastric formation of aluminum trichloride; (c) most but not all of the ingested antacid is utilized in acid neutralization in the stomach (average 78.6% in our 6 patients); and (d) antacid therapy does not modify the absolute rate of postprandial gastric emptying, but increases dilution of gastric contents, expanding the intragastric volume. Thus, the fractional gastric emptying rate declines, and this, in turn, should enhance antacid utilization by delaying its emptying.

Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats.

This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.

Prostaglandin generation from gastroduodenal mucosa: regional and species differences.

Regional and species differences in prostaglandin synthesis from gastroduodenal mucosa were assessed radiometrically. In the presence of excess added arachidonic acid substrate, corporal mucosa generated more prostanoid product per DNA than did antral or duodenal mucosa whether the whole homogenate or the microsomal fraction was used as an enzyme source. This appeared to be secondary to variability in cyclooxygenase activity and could not be explained by regional differences in the activity of enzymes competing for arachidonic acid substrate, in free endogenous arachidonic acid levels, in prostaglandin catabolizing activity, or in homogenate inhibitors. The qualitative product profile differed between species but not between regions within a species.

Neural isolation of the jejunoileum. Effect on tissue morphometry, mucosal disaccharidase activity, and tissue peptide content.

The aim of this study was to determine the effects of a model of intestinal extrinsic denervation on mucosal structure and function. Six dogs underwent in situ neural isolation of the jejunoileum (Group 2); six other dogs served as operated controls (Group 1), and five nonoperated dogs were naive controls (Group 3). Thirty-centimeter segments of proximal jejunum and distal ileum were excised before (time zero) and at 2 weeks and 8 weeks postoperatively in Groups 1 and 2, while similar regions were removed at time zero in Group 3. Tissues were analyzed for morphology with quantitative morphometry, mucosal disaccharidase activities (sucrase, maltase, and lactase), and tissue content of selected regulatory peptides in transmural, mucosa/submucosa, and muscularis regions. In situ neural isolation had no significant or consistent effects on morphology/morphometry or on mucosal disaccharidase activities. Tissue content of neuropeptide Y decreased markedly (P < 0.002) in all layers of the jejunal and ileal walls, but tissue content of vasoactive inhibitory polypeptide, substance P, cholecystokinin, neurotensin, met-enkephalin, neurokinin A, somatostatin, and calcitonin gene-related peptide demonstrated only minor changes. The physiologic effects of intestinal transplantation (extrinsic denervation and disruption of intrinsic, enteric neural continuity, and lymphatic drainage) have little effect on morphology, mucosal disaccharidase activity, and tissue content of most regulatory peptides. How these minor alterations might affect enteric function, however, needs to be investigated.

Intestinal transit of solid and liquid components of a meal in health.

The aim of this study was to test the hypothesis that, under physiologic conditions, the human small bowel discriminates between the solid and aqueous components of chyme, that is, that in a fashion analogous to the stomach, the intestine would allow the liquid fraction to progress at a faster rate than solid particles. To evaluate this hypothesis, we took advantage of a gamma-emitting solid marker, 131I-fiber, previously developed in our laboratory, that is recognized by the stomach as a solid and that is emptied at a slower rate than liquid markers. Thus, 131I-fiber enters the intestine during feeding at a slower rate than a liquid marker, being eventually excreted in the feces physically and chemically unchanged. We also developed a mathematical method to calculate the intestinal transit spectrum based on scintigraphic data obtained from 6 healthy individuals who ingested 131I-fiber and technetium 99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA)-water with a meal. The results disprove the hypothesis by showing that whereas 131I-fiber, as expected, leaves the stomach at a much slower rate than 99mTc-DTPA-water, both markers progress along the small bowel separately but at similar speeds. Our method for measuring intestinal transit provides a more comprehensive quantification of chyme transit in the human small bowel than earlier methods and should prove a useful technique for further noninvasive studies of transit after feeding.