Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI2) and PGE2, whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE2, were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE2 and PGI2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.

Is reperfusion injury an important cause of mucosal damage after porcine intestinal ischemia?

BACKGROUND: Intestinal ischemic injury is exacerbated by reperfusion in rodent and feline models because of xanthine oxidase-initiated reactive oxygen metabolite formation and neutrophil infiltration. Studies were conducted to determine the relevance of reperfusion injury in the juvenile pig, whose low levels of xanthine oxidase are similar to those of the human being. METHODS: Ischemia was induced by means of complete mesenteric arterial occlusion, volvulus, or hemorrhagic shock. Injury was assessed by means of histologic examination and measurement of lipid peroxidation. In addition, myeloperoxidase, as a marker of neutrophil infiltration, and xanthine oxidase-xanthine dehydrogenase were measured. RESULTS: Significant ischemic injury was evident after 0.5 to 3 hours of complete mesenteric occlusion or 2 hours of shock or volvulus. In none of these models was the ischemic injury worsened by reperfusion. To maximize superoxide production, pigs were ventilated on 100% O2, but only limited reperfusion injury (1.2-fold increase in histologic grade) was noted. Xanthine oxidase-xanthine dehydrogenase levels were negligible (0.4 +/- 0.4 mU/gm). CONCLUSIONS: Reperfusion injury may not play an important role in intestinal injury under conditions of complete mesenteric ischemia and low-flow states in the pig. This may result from low xanthine oxidase-xanthine dehydrogenase levels, which are similar to those found in the human being.

Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine.

BACKGROUND: Epidermal growth factor (EGF) signals enterocyte proliferation via extracellular regulated kinases (ERKs). Because glutamine is required for EGF-stimulated proliferation and stimulates ERKs in intestinal cell culture, we hypothesized that glutamine and the EGF-related peptide transforming growth factor-alpha (TGF-alpha) would synergistically enhance repair associated with stimulation of ERKs. METHODS: Thiry-Vella loops were created in juvenile pigs. One half of the loop was subjected to 2 hours of ischemia, and the other half served as control. Loops were infused daily with Ringer's solution containing 140 mmol/L glucose, 140 mmol/L glutamine, 140 mmol/L glucose plus 60 micrograms/L TGF-alpha, or 140 mmol/L glutamine plus 60 micrograms/L TGF-alpha. RESULTS: After 2 hours of ischemia, complete villous epithelial sloughing was present. By 18 hours, villous epithelium had fully restituted, but villi remained stunted until 144 hours after injury. Glutamine + TGF-alpha triggered sustained increases in ERK activity compared with glucose-treated tissues (maximal at 18 hours), whereas glutamine alone or glucose + TGF-alpha caused only transient elevations in ERK activity. By 72 hours, villous surface area had increased to normal values with glutamine plus TGF-alpha treatment, whereas villi remained stunted with glucose alone, glutamine alone, or glucose plus TGF-alpha. CONCLUSIONS: Glutamine plus TGF-alpha treatment restored mucosal architecture within 72 hours of severe ischemic injury associated with sustained elevations in ERK activity.

Neuro-immune pathobiology of infectious enteric disease.

Recent knowledge of neuro-endocrine-immune communication in the intestinal mucosa has provided a new paradigm for the pathophysiology of diarrheal disease that will significantly alter and advance therapeutic strategies. Mast cells, enteroendocrine cells and phagocytes are the proximate mediators of signalling cascades activated by parasitic nematodes and food allergens, enterotoxigenic bacteria, and at least some of the invasive pathogens, respectively. These proximate, trigger cells give rise to products that affect epithelial function directly, or indirectly through stimulation of prostaglandin production by mesenchymal cells, and enteric nerve stimulation, which can markedly amplify the initial stimulus. The enteric nervous system in fact may mediate the majority of the secretory response induced by enterotoxins or phagocytes. The signalling network mediated by cells in the lamina propria provides new points of control for pharmacological therapy.

The characteristics of intestinal injury peripheral to strangulating obstruction lesions in the equine small intestine.

Recent studies suggest that horses requiring surgical correction of strangulating intestinal obstruction may develop post operative complications as a result of ischaemia/reperfusion injury. Therefore, the mucosal and serosal margins of resected small intestine from 9 horses with small intestinal strangulating lesions were examined for evidence of ischaemia/reperfusion injury. Severe mucosal injury and marked elevations in myeloperoxidase activity were detected at ileal resection margins (n = 4), whereas the mucosa from proximal jejunal (n = 9) and distal jejunal (n = 5) resection margins was normal. However, the serosa from jejunal resection margins had evidence of haemorrhage and oedema, and the proximal jejunal serosa had significantly increased numbers of neutrophils. Histological injury in ileal stumps is indicative of the inability fully to resect the ileum in horses with distal small intestinal strangulations. One of 4 horses subjected to ileal resection was subjected to euthanasia and found to have a necrotic ileal stump. Evidence of serosal injury and neutrophil infiltration in the proximal jejunal resection margins may predispose horses to post operative adhesions. Four of 8 horses discharged from the hospital suffered from recurrent colic in the post operative period.

Gastric acid secretion in Basenji dogs with immunoproliferative enteropathy.

Gastric acid secretion was studied in 13 Basenji dogs with immunoproliferative enteropathy. Considerable variation in the severity of gastritis and enteritis existed among dogs. Basenji dogs were categorized into two groups on the basis of postmortem gastric and intestinal histology (group I, gastritis and enteritis; group II, only enteritis). Pentagastrin-induced gastric acid secretory capacity was increased (P less than 0.002) in group II dogs as compared to healthy Beagle controls. Gastric acid secretory capacity of Basenji dogs with gastritis and enteritis (group I) was not different from that observed in control dogs. Basal serum gastrin concentrations and secretin-stimulated serum gastrin concentrations of either group of Basenji dogs did not differ from controls. On the basis of symptomatology, Basenji dogs with diarrhea had significantly increased basal and postsecretin stimulation gastrin concentrations (P = 0.01) when compared with asymptomatic Basenji or healthy control dogs. These findings support a potential role for altered gastric acid secretory capacity in the pathogenesis of immunoproliferative enteropathy of Basenji dogs. Results of the secretin stimulation studies support previous pathologic studies that failed to detect gastrin-secreting tumors. Incorporated into this investigation was a trial to determine whether the combination of oxymorphone and acepromazine could be used for acid secretory studies. Compared to pentobarbital, which has been frequently used for acid secretory studies in a research setting, the drug combination resulted in increased gastric fluid volumes, a comparative increase in acid secretion, and a rapid uneventful recovery. We conclude that the combination of oxymorphone and acepromazine provides an acceptable means of restraint in dogs undergoing acid secretory studies.

Effects of diet and housing density on growth and stomach morphology in pigs.

Two experiments were conducted to evaluate the impact of housing density on the stomach morphology of growing pigs and determine whether there was an interaction between housing density and diet. All diets were corn-soybean meal based. In Exp. 1, 42 barrows (41.0+/-.95 kg BW) were allotted either individually or three pigs per pen to evaluate the effects of crowding on stomach lesions. Pen space per pig was 1.54 and .51 m2, respectively. All pigs were fed a finely ground and pelleted diet (610 microm) for 6 wk. The ADG decreased (P<.05) for the pigs housed three per pen during wk 4 to 6 only. There was no effect of housing density on feed intake or gain/feed ratio. Neither visual nor histological ulcer score differed between the two treatment groups. No stomachs were graded as normal. In Exp. 2, 80 barrows (39.8+/-.9 kg BW) were allotted either two or four pigs per pen. Pen space per pig was .77 and .39 m2, respectively. Half of the pigs in each housing situation were fed a coarse meal diet (1,050 microm), and half of the pigs were fed a finely ground and pelleted diet (577 microm) throughout the 49-d experimental period. Throughout the trial, pigs housed two per pen gained at a greater rate (P<.05) than pigs housed four per pen. From d 14 to the end of the trial, pigs consuming the finely ground and pelleted diet gained at a greater rate (P<.05) than pigs fed the coarse meal diet. The differences in ADG were reflected in final body weight. Stomach weight as a percentage of body weight was higher for animals on the coarse meal diet. Visual and histological ulcer scores were similar, and both were higher (P<.001) on the finely ground and pelleted diet, indicating greater damage. There was no effect of space restriction on stomach morphology. These data show the major effect of diet type on stomach lesions with no interaction with space restriction.

Effects of diets differing in propensity to promote gastric lesions on defense systems in gastric mucosae.

The objectives were to characterize biochemical changes, focusing on the antioxidant defense system, in stratified squamous and oxyntic mucosae in pigs fed diets with differing propensity to promote gastric lesions. Barrows (n = 24; 48.7+/-1.0 kg BW) housed in individual pens were used in the experiment. Barrows were fed a corn-soybean meal diet. Half of the animals were fed the diet as a coarsely ground meal (CGM; average particle size = 886 microm), and half were fed the diet as a finely ground pelleted (FGP; average particle size = 528 microm) feed. Initiation and termination of the experiment were staggered over a 3-wk period. Diets were fed for 6 wk. Visual evaluation of the stratified squamous mucosa of the proximal stomach showed increased (P<.001) damage in animals fed the FGP diet. These results were supported by histological evaluation. Thiobarbituric acid-reacting substances (TBARS), indicative of peroxide generation, relative to amount of protein were higher (P<.001) in stratified squamous than in oxyntic mucosa, and, per unit of tissue, TBARS were highest in stratified squamous mucosa of animals fed the FGP diet. Glutathione peroxidase activity followed a pattern similar to that of peroxides. Prostaglandin E2 was higher (P<.004) in stratified squamous than in oxyntic mucosa. In contrast, the activity of catalase was higher (P<.001) in oxyntic mucosa and was not affected by diet. The data show differences in the production of peroxides, the antioxidant defense system, and PGE2 between stratified squamous and oxyntic mucosae. Generation of prooxidants and the antioxidant defense system may play a role in the predilection of ulcers for the stratified squamous mucosal region of the pig stomach.

Physiological responses in swine treated with water containing sodium bicarbonate as a prophylactic for gastric ulcers.

Maintenance of gastric pH above 4.0 aids the prevention of bile acid-mediated ulcerative damage to the pars esophageal tissue in pigs. One means of doing so is the addition of buffering compounds, such as sodium bicarbonate, to the water supply; however, any potential physiological effect of buffer consumption has yet to be determined. Experiment 1 tested the acute effects of buffer addition to the water supply on systemic acid-base and electrolyte balance in swine (BW 40.7 +/- 3.0 kg). Consumption of water calculated to a 200 mOsm solution with sodium bicarbonate for 24 h increased (P < 0.05) blood Na+, HCO3(-), and pCO2, although these effects were all within physiologically tolerable levels. Urine pH and Na+ excretion increased (P < 0.001) following the consumption of NaHCO3, with Na+ concentration almost threefold higher in treated pigs compared with controls. Experiment 2 determined the chronic systemic effects of buffer consumption by measuring blood and urine variables, with pigs consuming NaHCO3-treated water throughout. Water consumption increased (P < 0.001) during buffer consumption, although intake levels remained within normal ranges. Blood pH levels were not affected by long-term consumption of dietary buffer; however, blood HCO3(-) (P < 0.05), Na+, and pCO2 (P < 0.01) increased. Urine pH and urine Na+ concentration increased (P < 0.01) in buffer-treated compared with control animals. Results indicate that sodium bicarbonate can safely be added to the water supply for pigs, with no clinically relevant alterations in acid-base balance because the animals readily compensate for buffer intake.

Effects of feed physical form and buffering solutes on water disappearance and proximal stomach pH in swine.

The effects of the physical form of feed on water disappearance and the effects of buffered water on proximal stomach pH in swine were determined in two experiments. In Exp. 1, 32 barrows were used to evaluate the water disappearance in pigs fed a finely ground and pelleted diet vs those fed a coarsely ground and mashed diet for ad libitum consumption over a 2-wk interval. There were four replicates with eight pigs per replicate. Average daily water and feed disappearance did not differ (P = 0.06 and P = 0.10, respectively). However, average daily water to feed ratio was higher for pigs on the pelleted diet (4.21+/-0.31 L/kg vs 3.04+/-0.33 L/kg; P = 0.02). The higher ratio for the pelleted diet indicated that this may be the cause of a more fluid digesta allowing reflux of irritants from the distal stomach to damage the pars esophageal region of the proximal stomach. In Exp. 2, four barrows (25+/-2 kg) had gastric cannulas surgically implanted into the proximal region of the stomach. Pigs were given ad libitum access to a finely ground and pelleted diet. The experimental design was a Latin square. Water treatments included water (control), 200 mOsm NaHCO3, 250 mOsm NaHCO3, and 250 mOsm mono-dibasic sodium phosphate. Pigs were given a 4-d adjustment period, and pH measurements began on the morning of the 5th d and continued for 24 h under normal feeding conditions. Feed was removed and measurements were continued for 16 h. Buffered water raised the pH of the proximal region of the stomach compared to the control (P < 0.001). Average pH while consuming the water treatments was 3.65+/-0.11 (n = 4) for water control, 4.86+/-0.11 (n = 4) for the 200 mOsm NaHCO3, 4.63+/-0.11 (n = 4) for the 250 mOsm NaHCO3, and 4.59+/-0.14 (n = 3) for the 250 mOsm mono-dibasic sodium phosphate. Buffers also raised the pH of the proximal region of the stomach for the fed (P < 0.001) and the feed restriction (P < 0.01) phases of the trial. Water disappearance rates in pigs given NaHCO3 were higher than in the control (P < 0.01). Average daily water disappearance for the treatments was 9.13+/-0.74 L for the control, 13.56+/-0.74 L for 200 mOsm NaHCO3, 13.77+/-0.74 L for the 250 mOsm NaHCO3, and 10.33+/-0.95 L for the phosphate buffer. The proximal pH of the stomach was increased by adding buffers to the water supply. Addition of NaHCO3 buffers also caused increased water disappearance.

Changes in gastric contents in pigs fed a finely ground and pelleted or coarsely ground meal diet.

The objective was to characterize the change in stomach contents in relation to time after feeding between pigs consuming a restricted amount of a finely ground and pelleted (FGP) or coarsely ground meal (CGM) diet. Particular interest was placed on the concentration of organic acids and ammonia, the products of microbial fermentation. Thirty barrows were ranked by weight and assigned to a postfeeding time of 2, 4, 6, 8, or 12 h and either the FGP or CGM diet. Initiation and termination of the experiment were staggered over a 2-wk period. The treatment period was 42 d. Percentage of dry matter was higher (P<.01) in the stomach contents of pigs on the CGM diet. Concentrations of pepsin and protein were higher (P<.05) and ammonia tended to be higher (P = .10) in the proximal stomach of pigs fed the FGP diet. In contrast, concentrations of acetate and L-lactate were higher (P<.05) in the proximal stomach of pigs fed the CGM diet. All pigs on the CGM diet had stomachs that graded as normal on visual inspection. There was variable damage to the stomachs of pigs on the FGP diet. Measurement of chromium concentration in the stomach after an oral dose of Cr-EDTA clearly demonstrated the mixing that occurs between the proximal and distal stomach by 2 h after feeding in pigs consuming the FGP diet, whereas a gradient was maintained in pigs consuming the CGM diet. Thus, components normally secreted in the distal stomach return to the proximal stomach. These data show that components secreted in the distal region, such as acid and pepsin, may play a role in initiating damage to the stratified squamous mucosa. High concentrations of organic acids in the stomach of pigs on the CGM diet were not associated with damage to the stratified squamous mucosa in the esophageal region.

Effects of slaframine on ruminant digestive function: liquid turnover rate and fermentation patterns in sheep and cattle.

Two trials were initiated to determine if slaframine (SF) can be used to alter fluid digesta flow and fermentation patterns in the rumen. In trial 1, a preliminary experiment, four Dorset X Barbados Black-belly ruminal-cannulated wethers (avg weight 41.6 8.7 kg) given ad libitum access to a pelleted concentrate/hay diet were injected intramuscularly with 0, 12, 24 or 48 micrograms SF/kg body weight (BW) in a 4 X 4 Latin-square design. Ruminal fluid dilution rate was determined using a single intraruminal infusion of polyethylene glycol (7 g), followed by seven hourly ruminal fluid samples. The administration of 48 micrograms SF/kg BW increased (P less than .10) ruminal volume and outflow by 27 and 25%, respectively, compared with controls. In trial 2, two Hereford and two Angus ruminal cannulated steers (avg weight 568 +/- 93 kg) were injected with 0, 6, 12 or 24 micrograms SF/kg BW at 8-h intervals over a 24-h period in a 4 X 4 Latin-square design. Steers were fed a concentrate diet at twice maintenance in 24 equal portions daily. Ruminal fluid dilution was measured using a single intraruminal infusion of cobalt-ethylenediamine tetraacetic acid (20 g) administered 9 h after the initial SF injection. Ruminal fluid was collected each hour during 8 to 24 h after the initial SF injection and analyzed for pH, osmolality and volatile fatty acids (VFA).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose-stimulated fluid absorption in the pig small intestine during the early stage of swine dysentery.

Kinetics of glucose-stimulated water absorption and small bowel absorptive function in normal pigs and pigs affected with swine dysentery were examined with a steady-state perfusion technique. Glucose-dependent stimulation of solute and water absorption was shown in normal pigs with a transport constant of 46.9 mM and a maximum change in volume transport capacity of 78.3 ml/h/50 cm of jejunum. The entire small intestine of normal pigs absorbed 10 mg/min of an isotonic fluid when the luminal glucose concentration was 80 mM, whereas the intestine secreted 3 ml/min when glucose was replaced by mannitol. These absorptive and secretory rates in infected pigs were identical to those in control pigs. Electrolyte and acid-base values in arterial blood were unchanged after the rapid administration of 500 ml of a glucose-electrolyte solution into the proximal portion of the small bowel, and the plasma glucose response in control and infected pigs was identical. Seemingly, small bowel absorptive function is normal in pigs with swine dysentery and provides a rational approach to oral, glucose-electrolyte therapy for restoring the extracellular fluid losses that occur with this disease.

Ion transport by the pig colon: effects of time and anesthesia.

A method for temporarily isolating a 50-cm loop of ascending spiral colon in the pig allowed a study of the effect of halothane anesthesia on colonic absorption without complications of acute surgical trauma, and provided a means to obtain timed samples of the colonic solution. Test solutions instilled into the loop consisted of a volatile fatty acid solution, similar in composition to normal colonic contents, and a Ringer solution. Ther was no apppreciable change in the rate of net solute absorption in conscious or anesthetized animals in repeated 1-hour determinations over a 6-hour period, provided the cardiovascular and arterial acid base variables remained stable. Net rates and direction of individually transported solutes and H20 were essentially unaffected by anesthesia during 2-hour experimental periods. However, net solute changes in this closed-loop system were not constant during individual absorption periods. These changes were due to a volume dependence on the rate of net absorption and a rapid dissipation of the driving forces initially present. Failure to recognize these time-dependent changes may leas to serious misinterpretations of the results.

Mechanisms of acid injury in porcine gastroesophageal mucosa.

OBJECTIVE: To identify the cause and mechanisms of injury in gastroesophageal ulcer disease in market weight swine. DESIGN: Comparison of mechanisms of injury caused by HCI with those caused by short chain fatty acids (SCFA) in gastric mucosa. ANIMALS: Pigs weighing 30 to 40 kg. PROCEDURE: Gastric tissues were studied in Ussing chambers; short-circuit current (lsc) and electrical resistance (R) were recorded in response to treatment, and tissues were examined histologically. RESULTS: 60 mM mucosal acetate abruptly ( < or = 75 minutes) and irreversibly abolished lsc at pH < or = 4.5, whereas R decreased more slowly. These data were associated with cell swelling and vesicle formation in mid-zonal layers, followed by sloughing of the outer barrier, erosion into deeper zones, and finally, ulceration. Mucosal HCl at pH > 1.5 was ineffective; however, at pH 1.5, HCl induced an abrupt decrease in R, followed by a slow decrease in lsc, an effect opposite to that caused by SCFA. Serosal addition of HCl rapidly abolished lsc suggesting a barrier to free H+ diffusion from the mucosal solution. CONCLUSIONS: Undissociated SCFA rapidly penetrate the outer barrier and acidify underlying viable tissue. Cellular acidification inhibits Na pumping and osmoregulation, resulting in cell swelling and necrosis. In contrast, HCl induces and increase in outer barrier permeability before accessing the transporting cells, a much longer process ( > or = 5 hours) requiring a lower pH. These studies suggest that microbial production of SCFA may be important in the pathogenesis of porcine gastric ulcers.

Comparison of the effects of disodium ethylenediaminetetraacetate, theophylline, and deoxycholic acid on colonic ion transport and permeability.

The effects of ethylenediaminetetraacetate (EDTA), theophylline, and deoxycholic acid (DCA) on colonic ion transport and permeability were examined in an isolated loop system of the pig colon. The 3 agents abolished net water absorption, but only EDTA and DCA induced an increase in mucosal permeability. Theophylline resulted in active bicarbonate secretion and increased the transmural electrical potential difference, whereas DCA resulted in a dose-dependent inhibition of the theophylline-stimulated potential difference and antagonized or abolished the effect of theophylline on ion transport. A similar inhibition of the sodium transport potential across the mucosa resulted with DCA. The effects of DCA on the potential difference were immediate and reversible and paralleled the changes in colonic permeability. These results are consistent with the hypothesis that the mechanism of bile acid-induced diarrhea is through an increase in mucosal permeability and/or mucosal damage. Evidence of an active secretory process was not demonstrable with this preparation.

Endogenous prostanoids control ion transport across neonatal porcine ileum in vitro.

In contrast to the net absorption of Na and Cl ions observed in vivo, porcine small intestine had a net secretion of these ions in vitro. These discrepancies between in vivo and in vitro results have led to difficulties in interpretation of studies investigating mechanisms of intestinal secretion and diarrhea in this species. To examine the influence of endogenous prostanoids on ion transport in neonatal porcine ileum in vitro, tissues were prepared and studied in indomethacin. Net absorption of Na, reversal of net Cl secretion to net absorption, and decreased short circuit current were observed. Conversely, addition of prostaglandins to indomethacin-treated tissues reversed these effects and reestablished conditions similar to those observed in control tissues. Control tissue was essentially refractory to the effects of exogenous prostaglandins. Results indicate that under in vitro conditions, ion transport in neonatal porcine ileum is tightly regulated by endogenous prostanoids that abolish the neutral NaCl absorptive mechanism and elicit electrogenic Cl secretion. However, concentrations of these prostanoids may have been artificially high as a result of tissue preparation for in vitro study.

Effects of acetate on absorption of solute and water from the pig colon.

The effect of acetate, at physiologic concentrations, on sodium and water absorption in the temporarily isolated colon of the conscious pig was studied with isotonic perfusion solutions buffered at pH 6.4 or 7.4, in which either chloride or acetate was present as the major anion. Sodium and water absorption was greater from the acetate solution when the pH was low; however, acetate reduced sodium and water absorption below that observed with the chloride solution when the pH was high. There were no significant differences observed in sodium or water absorption from the chloride solution at either pH. We conclude that the concentration of undissociated acetate influences sodium and water absorption in the colon of the pig. Such an effect may have important consequences on the reserve absorptive capacity of the colon in certain diarrheal diseases.

Absorption of volatile fatty acid, Na, and H2O by the colon of the dog.

Volatile fatty acid (VFA) concentrations were examined in the gastrointestinal tract of dogs 24 and 48 hours after a meal. Small concentrations of VFA were present in the stomach and small intestine. Large concentrations were present in the large intestine at both periods after the meal, but the total quantity was reduced markedly between 24 and 48 hours. Colonic absorption and transport of VFA also were examined with in vitro and in vivo perfusion procedures. Both demonstrate that VFA were rapidly absorbed and that the rate of absorption/cm2 of colonic mucosa ws equivalent to that measured in the pig. In vivo results showed that VFA and Na were absorbed at the same rate, and their absorption showed a parallel increase with a decrease in pH of the perfusate. Absorption of Na and VFA alone could account for osmotic absorption of H2O from the colon. Results indicated that although the total quantity of VFA absorbed by the colon of the dog would be nutritionally insignificant, their absorption is of major importance to normal colonic absorptive processes.

Pathophysiologic features of swine dysentery: cyclic nucleotide-independent production of diarrhea.

Net electrolyte and water transport and unidirectional Na+ fluxes were examined in ligated colonic loops of clinically normal pigs and in pigs with swine dysentery (etiologic agent Treponema hyodysenteriae) in the presence or absence of theophylline. In normal pigs, theophylline abolished net Na+ absorption via a reduction in the lumen-to-blood flux, decreased Cl- absorption, and increased HCO3- accumulation in the lumen. In infected pigs, all net ion transport was abolished, with the addition of theophylline producing little effect. The absence of net Na+ absorption in infected pigs was also the result of a decreased lumen-to-blood flux. Seemingly, colonic malabsorption may be the primary transport alteration in swine dysentery. Concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in samples of colonic mucosa from normal and infected pigs after in vitro exposure to a Ringer's solution containing 0 or 20 mM theophylline. Basal values of cAMP or cGMP did not increase in infected colonic mucosa. There was a diminished capacity of the infected mucosa to respond to theophylline. Alterations in ion transport in conjunction with measurements of cAMP and cGMP indicated that the pathogenic mechanism(s) in swine dysentery were not similar to those of Salmonella, Shigella, Vibrio cholerae, or Escherichia coli diarrhea.