Experimental Small Bowel Research Articles

Experimental small bowel transplantation using newborn intestine in rats: II. Revascularization of newborn intestine is independent of vascular endothelial growth factor

Background : Fetal and newborn intestine often are revascularized after subcutaneous transplantation without surgical vascular anastomosis. However, the mechanism of this ability remains unclear. Methods : First, the ability of natural revascularization in newborn organs was tested. Newborn organs in whole (liver, kidney, heart, intestine, spleen, and pancreas) were grafted into the subcutaneous tissue of the adult rat and evaluated histopathologically 2 weeks after transplantation. Second, expression of vascular endothelial growth factor (VEGF) mRNA in the intestinal graft was determined before and after transplantation. Finally, we tested whether the free graft survival of newborn intestine was interrupted by TNP-470, an antiangiogenic agent. Results : Spleen and intestine were revascularized at a higher rate (91.6%, 75%, respectively), and kidney and heart grafts survived at a lower rate (41.7%, 25%, respectively). But all of liver and pancreas grafts failed to be revascularized. VEGF mRNA was not induced in the course of revascularizing. Furthermore, TNP-470 did not interfere with neovascularization of the newborn intestinal graft in vivo. Conclusions : Each organ had an organ-specific angiogenic activity. Neovascularization of intestinal graft was not dependent on VEGF expression.

Expression of NOS II and its role in experimental small bowel ulceration in rats

Background: Overproduction of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD). Methods: We observed the expression and localization of inducible NO synthase (NOS-II) in small intestinal ulceration induced by indomethacin in rats. The role of NO was investigated by using NO synthase inhibitors. Results: The small intestine was affected by longitudinal ulcers after indomethacin administration and ulceration was associated with distinctive expression of NOS-II protein and mRNA. The amount of its expression was found to correlate with the extent of inflammation. Histologically, both immunohistochemistry and in situ hybridization revealed a similar localization of NOS-II to inflammatory and epithelial cells. The possible amelioration of the inflammation was modulated by aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME) treatment for 10 days. Both AG and L-NAME attenuated intestinal myeloperoxidase activity and gross inflammation, only AG was found to decrease intestinal permeability with a significant amelioration of body weight loss. Conclusion: These findings indicate that NO derived mainly from inflammatory cells may play an important role in the pathophysiology of intestinal ulceration and offer the potential for future treatment directed at blocking neutrophils recruitment and NO overproduction in IBD. (Surgery 1999;126:553-61.)

Insulin-like growth factor-1 modulation of intestinal epithelial cell restitution.

After superficial intestinal injury, the mucosal integrity is reestablished by rapid migration of epithelial cells from the adjacent area in a process called restitution. Our previous study suggested that growth hormone improves intestinal healing in an experimental small bowel ulceration, mediated by insulin-like growth factor-1 (IGF-1). The aim of the present study was to assess the role of IGF-1 in mucosal epithelial restitution using an in vitro epithelial wound model. Wounds were established in confluent monolayers of the intestinal cell line, IEC-6. Migration was quantitated in the presence or absence of IGF-1 as the number of cells migrating across the wound edge. Proliferation was assessed by thymidine incorporation. IGF-1-enhanced epithelial cell migration by 2- to 2.5-fold after 12- and 24-hour treatment, respectively, the first step involved in gastrointestinal wound healing. Cell proliferation was significantly stimulated by IGF-1 as well. In addition, expression of transforming growth factor-beta (TGF-beta) mRNA was significantly enhanced in the wounded monolayers treated with IGF-1. IGF-1 receptor mRNA was found to be detectable throughout the gastrointestinal mucosa and in the intestinal epithelial cells. In conclusion, these findings suggest that IGF-1 plays an important role in reconstitution of intestinal epithelial integrity after mucosal injury.

Expression of NOS II and its role in experimental small bowel ulceration in rats

Overproduction of nitric oxide (NO) has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease (IBD). We observed the expression and localization of inducible NO synthase (NOS-II) in small intestinal ulceration induced by indomethacin in rats. The role of NO was investigated by using NO synthase inhibitors. The small intestine was affected by longitudinal ulcers after indomethacin administration and ulceration was associated with distinctive expression of NOS-II protein and mRNA. The amount of its expression was found to correlate with the extent of inflammation. Histologically, both immunohistochemistry and in situ hybridization revealed a similar localization of NOS-II to inflammatory and epithelial cells. The possible amelioration of the inflammation was modulated by aminoguanidine (AG) and NG-nitro-L-arginine methyl ester (L-NAME) treatment for 10 days. Both AG and L-NAME attenuated intestinal myeloperoxidase activity and gross inflammation, only AG was found to decrease intestinal permeability with a significant amelioration of body weight loss. These findings indicate that NO derived mainly from inflammatory cells may play an important role in the pathophysiology of intestinal ulceration and offer the potential for future treatment directed at blocking neutrophils recruitment and NO overproduction in IBD.

Experimental small bowel transplantation using newborn intestine in rats: I. Lipid absorption restored after transplantation of nonvascularized graft

Background/Purpose: Utilizing the characters of neovascularized activity of newborn organs, the authors developed a rat model of small bowel transplantation with a free graft of newborn intestine into the recipient's omentum. Methods: Segmental intestine from newborn rats were grafted into the omentum without vascular anastomosis in a syngeneic combination (n = 19). The transplanted intestine was examined morphologically and electrophysiologically 4 weeks after grafting. Then, recipients' small intestine was totally substituted by the transplanted newborn intestine, and recipients' survival was recorded after orthotopical reconstruction. During the experimental periods, feces of these rats were collected, and total lipid excretion was measured. The shortgut rats, whose small bowel was totally resected, served as a control (n = 12). Results: Thirteen of 19 grafts (68.4%) were judged as a histologically mature intestine. They showed typical slow waves that were identical to those of native small intestine. After all of the mature grafts were interposed, six recipients (46.2%) survived longer than 15 weeks. Control short gut animals severely lost weight and died except for one. Conclusion: Newborn intestinal transplantation could restore severe weight loss in the short-gut rats and save them.

Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.

We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.

New functions for the aryl hydrocarbon receptor

HepatologyVolume 23, Issue 2 p. 379-380 Hepatology ElsewhereFree Access New functions for the aryl hydrocarbon receptor D A Brenner, D A BrennerSearch for more papers by this author D A Brenner, D A BrennerSearch for more papers by this author First published: February 1996 https://doi.org/10.1002/hep.510230228Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Nebert DW. The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects. Toxicology 1989; 20: 153– 174. 2 Birnbaum LS. Evidence for the role of the Ah receptor in response to dioxin. Prog Clin Biol Res 1994; 387: 139– 154. 3 Okey AB, Riddick DS, Harper PA. Molecular biology of the aromatic hydrocarbon (dioxin) receptor. Trends Pharmacol Sci 1994; 15: 226– 232. 4 Okey AB, Riddick DS, Harper PA. The Ah receptor: mediator of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Toxicol Let 1994; 70: 1– 22. 5 Puga A, Nebert DW, Carrier F. Dioxin induces expression of c-fos and c-jun proto-oncogenes and a large increase in transcription factor AP-1. DNA Cell Biol 1992; 4: 269– 281. 6 Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SST, Kimura S, Nebert DW et al. Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 1995; 268: 722– 726. 7 Dohr O, Vogel C, Abel J. Modulation of growth factor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Exp Clin Immunogenet 1994; 11: 142– 148. 8 Sutter TR, Guzman K, Dold KM, Greenlee WF. Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleu-kin-1b. Science 1991; 254: 415– 418. 9 Licthman SN, Keku J, Clark RL, Schwab JH, Sartor RB. Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Hepatology 1991; 13: 766– 772. 10 Lichtman SN, Keku J, Schwab JH, Sartor RB. Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology 1991; 100: 513– 519. 11 Lichtman SN, Keku J, Schwab JH, Sartor RB. Evidence for pep-tidoglycan absorption in rats with experimental small bowel bacterial overgrowth. Infect Immunol 1991; 59: 555– 562. Citing Literature Volume23, Issue2February 1996Pages 379-380 ReferencesRelatedInformation

Reactivation of arthritis induced by small bowel bacterial overgrowth in rats: role of cytokines, bacteria, and bacterial polymers

Arthritis is often associated with intestinal diseases, but the etiology is not known. We developed a rat model whereby arthritis was reactivated by experimental small bowel bacterial overgrowth (SBBO). Self-limited monoarticular arthritis was induced by intra-articular injection of 2 micrograms of rhamnose peptidoglycan-polysaccharide derived from group A streptococci into the ankle joints in female Lewis rats. Eleven days after intra-articular injection, when swelling was resolving, experimental SBBO induced by surgical creation of jejunal self-filling blind loops reactivated arthritis, but SBBO induced by creation of self-emptying blind loops, which minimally increases luminal bacteria, and sham operation did not (P < 0.001). Increased joint diameters in rats with self-filling blind loops persisted for at least 56 days after surgery. Reactivation of arthritis due to SBBO was prevented by anti-tumor necrosis factor alpha antiserum and interleukin 1 receptor antagonist (P < 0.001), indicating that these cytokines mediate joint swelling secondary to intestinal injury. Recombinant bactericidal/permeability-increasing protein, an agent which neutralizes endotoxin, and metronidazole, which is active against anaerobic bacteria, prevented arthritis (P < 0.001), but polymyxin B (which also neutralizes endotoxin) and gentamicin had no effect. Mutanolysin, an enzyme which degrades peptidoglycan-polysaccharide from group A streptococci, exacerbated arthritis for the first 6 days but then diminished joint swelling from 12 to 21 days after surgery (P < 0.001). These studies introduce a reproducible animal model of reactivation of arthritis secondary to intestinal injury and demonstrate a role for bacterial products from endogenous enteric organisms.

Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction

One feature of enteric mucosal immunity is oral tolerance (OT), a state of diminished systemic immune responsiveness to an antigen induced by previous oral feeding of that antigen. Because OT induction requires an interaction between the intestinal and systemic immune systems, the authors plan to use it as a method in experimental small bowel transplantation (SBT) to evaluate the ability of the intestinal allograft to cooperate immunologically with the host. Two different methods have been used in experimental SBT to establish graft venous drainage: anastomosis of the graft mesenteric vein to the recipient portal vein or to the inferior vena cava. This experiment was designed to examine the role of the intestinal venous drainage routes in OT induction. Rats with a surgically created mesenterico-caval shunt (MCS) and their sham controls received an immunization protocol to induce OT to ovalbumin. The results showed that OT was readily induced in the sham animals, but not in the animals with MCS. These results indicate that intestinal venous drainage through the liver plays a central role in OT induction. Therefore, future analyses of OT in allogeneic SBT will require an animal model with portal venous drainage of the intestinal graft.

A Comparison of the Healing Process of Two Single-Layer Suture Techniques for Experimental Small Bowel Anastomosis

A comparison was made between the effect of the Gambee technique with inversion of the serosa and a submucosa technique on wound healing in small bowel anastomoses of 15 pigs. The submucosa technique avoids a broad serosal contact by burying the horizontally placed suture sling in the submucosal layer. Polydioxanon 4-0 and 6-0 served as suture material. Two anastomoses of each technique were constructed in one animal. Five animals were sacrificed after 4 days, 3 weeks, and 3 months, respectively. The anastomoses were evaluated by gross appearance, microangiography and histology. The submucosa technique resulted in a significant smaller scar with fewer necrotic areas (p < 0.01). It did not compromise the blood vessels in the knot area. This improved wound healing demonstrates that anastomotic healing does not necessitate broad serosal contact. Therefore, the submucosa technique may be considered for anastomoses of the compromised gut.

Biliary tract disease in rats with experimental small bowel bacterial overgrowth

Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography. Lewis and Wistar rats with self-filling blind loops had thickening of the cross-sectional area of the extrahepatic bile ducts compared with controls and nonsusceptible Buffalo rats (p < 0.001). Daily metronidazole therapy significantly reduced thickening of bile ducts in Lewis and Wistar rats with self-filling blind loops. Bile flow was increased in Lewis and Wistar rats with blind loops compared with controls (p < 0.05). Cholangiograms of Lewis and Wistar rats with self-filling blind loops demonstrated extrahepatic ductal dilatation and ectasia with irregular, beaded, rapidly tapering and tortuous intrahepatic ducts. Blinded cholangiographical scores of susceptible rat strains with self-filling blind loops were higher (score = 5.9 ± 2.3) than those of controls (1.2 ± 0.4), rats with blind loops treated with metronidazole (0.8 ± 1.3) and nonsusceptible Buffalo rats with blind loops (0.6 ± 0.9) (p < 0.01). Biliary histological and cholangiographical abnormalities found in this rat model resemble features of primary sclerosing cholangitis. This animal model will be useful in exploring mechanisms of the association of hepatobiliary inflammation with intestinal injury and investigating potential therapeutic agents. (HEPATOLOGY 1990;13:766–772.)

Biliary tract disease in rats with experimental small bowel bacterial overgrowth

Small bowel bacterial overgrowth, which develops in surgically created jejunal self-filling blind loops, is associated with hepatic injury in susceptible rat strains. The histological findings are portal tract inflammation and bile duct proliferation and destruction. In this study, evidence of injury to the extrahepatic and intrahepatic bile ducts in susceptible and resistant inbred rats with self-filling blind loops was determined by bile flow rates, histological appearance of cross-sections of bile ducts and cholangiography. Lewis and Wistar rats with self-filling blind loops had thickening of the cross-sectional area of the extrahepatic bile ducts compared with controls and nonsusceptible Buffalo rats (p less than 0.001). Daily metronidazole therapy significantly reduced thickening of bile ducts in Lewis and Wistar rats with self-filling blind loops. Bile flow was increased in Lewis and Wistar rats with blind loops compared with controls (p less than 0.05). Cholangiograms of Lewis and Wistar rats with self-filling blind loops demonstrated extrahepatic ductal dilatation and ectasia with irregular, beaded, rapidly tapering and tortuous intrahepatic ducts. Blinded cholangiographical scores of susceptible rat strains with self-filling blind loops were higher (score = 5.9 +/- 2.3) than those of controls (1.2 +/- 0.4), rats with blind loops treated with metronidazole (0.8 +/- 1.3) and nonsusceptible Buffalo rats with blind loops (0.6 +/- 0.9) (p less than 0.01). Biliary histological and cholangiographical abnormalities found in this rat model resemble features of primary sclerosing cholangitis. This animal model will be useful in exploring mechanisms of the association of hepatobiliary inflammation with intestinal injury and investigating potential therapeutic agents.

Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth

Surgical creation of jejunal self-filling blind loops (SFBL) causes small bowel bacterial overgrowth which is associated with hepatobiliary inflammation in the susceptible Lewis and Wistar rat strains. Since hepatic injury occurs when small bowel anaerobic bacterial concentrations are increased 4 to 6 log10 units per ml and hepatic bacterial cultures are negative, we postulate that the inflammation is caused by absorption of phlogistic cell wall polymers originating from bacteria within the loop. To demonstrate absorption of bacterial cell wall polymers, we measured plasma and hepatic levels of immunoreactive peptidoglycan-polysaccharide (PG-PS) following intraluminal injection as well as anti-PG antibodies as an indirect measure of absorption and/or accumulation of endogenous PG. PG-PS purified from group A streptococci was detected in plasma by enzyme-linked immunosorbent assay after intraluminal injection; rats with SFBL showed significantly more uptake into plasma and the liver than sham-operated rats or SFBL rats which were treated with metronidazole (P less than 0.025). Total plasma immunoglobulin A (IgA), IgG, and IgM levels did not differ among sham-operated rats and those with self-emptying blind loops or SFBL, but plasma anti-PG IgA (P less than 0.05), IgG, and IgM (P less than 0.01) levels were increased in rats with SFBL. Metronidazole and tetracycline prevented the elevation of anti-PG antibody, but gentamicin and polymyxin B did not. Anti-lipid A, anti-soy protein, and anti-chow antibodies in plasma were not consistently increased in rats with SFBL indicating the lack of a generalized antibody response to luminal antigens. These data suggest that PG from normal flora bacteria is absorbed from the intestinal lumen and that mucosal injury and/or increased luminal concentrations of PG, such as those induced by small bowel bacterial overgrowth, lead to enhanced absorption of potentially inflammatory bacterial polymers.

Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth.

Evidence for peptidoglycan absorption in rats with experimental small bowel bacterial overgrowth.

Hepatic inflammation in rats with experimental small intestinal bacterial overgrowth

Hepatobiliary inflammation and other extraintestinal manifestations accompany certain intestinal disorders, perhaps because of proliferation or enhanced transport of luminal bacteria or their phlogistic cell-wall components. Using jejunal self-filling blind loops to create small bowel bacterial overgrowth, we compared biochemical and histological evidence of hepatic inflammation in 3 rat strains chosen for their variable inflammatory responses to bacterial cell wall polymers. Lewis and Wistar rats developed weight loss, hepatomegaly, and hepatic inflammation 4 and 12 wk, respectively, after creation of SFBL. Plasma aspartate aminotransferase levels in Lewis rats 4 wk (578 ± 77 U/L) and Wistar rats 12 wk (220 ± 35 U/L) after self-filling blind loops were significantly greater than in rats with self-emptying blind loops (112 ± 24 U/L, p < 0.001; 104 ± 22, p < 0.05) or sham-operated Lewis (84 ± 24, p < 0.001) or Wistar (78 ± 10, p < 0.001) rats. Randomized comparison using a histology grading score showed abnormalities that parallelled aminotransferase values. Lewis and Wistar rats with self-filling blind loops had hepatic injury with bile duct proliferation, fibrosis and acute and chronic periportal and focal parenchymal inflammation. Lewis and Wistar rats with self-emptying blind loops developed occasional mild histologic lesions. 50% of Lewis rats with self-filling blind loops for 4 wk died compared with only 15% in other groups. However, Buffalo rats with self-filling blind loops developed no weight loss, hepatomegaly, or hepatic injury. Anaerobic cultures of blood, peritoneum and liver were negative in all strains. Diet-restricted, sham-operated Wistar rats with weights similar to the Wistar rats with self-filling blind loops did not develop histologic abnormalities or elevated aminotransferase levels (76 ± 31 U/L). These results show that experimental small bowel bacterial overgrowth causes significant hepatic inflammation leading to fibrosis in susceptible rat strains. Caloric deprivation and hepatic bacterial invasion are not etiologically responsible. We suggest that bacterial cell wall polymers or other bacterial toxins from the blind loop cause hepatic lesions in genetically susceptible hosts.

A Successful Model of Small Bowel Autotransplantation in the Dog

Experimental small bowel transplantation has continued to be a complex procedure with high mortality. We investigated the technical aspects of small bowel transplantation in an effort to define a procedure that would result in an improved survival rate. Three methods of graft harvesting were examined in a model of canine small bowel autotransplantation. Harvesting the graft by first flushing with room-temperature lactated Ringer's followed by iced lactated Ringer's resulted in the best preservation and subsequently the best survival rate (71%). Flushing with iced lactated Ringer's alone resulted in survival rates of 22 and 50% in two additional groups. We also investigated two methods of graft reanastomosis. Although either venous drainage regimen appears to be suitable, graft venous reanastomosis to the host portal vein resulted in a slightly higher postoperative weight than reanastomosis to the host inferior vena cava. A model of small bowel transplantation with a high long-term survival rate has been developed. This model can now be applied to studies of the various physiological aspects of small bowel transplantation.

Cytoprotective agents in experimental small bowel volvulus

An accepted experimental model for midgut volvulus was used to produce small bowel strangulation obstruction of 48 hours duration in Sprague-Dawley rats. A 93% perioperative mortality rate resulted after release of the volvulus. Treatment with three cytoprotective agents at the time of volvulus release resulted in the following mortality rates: superoxide dismutase, 89%; ibuprofen, 50%; prostaglandin E1 (PGE1, 11%. The predominant cause of death in all treatment groups was bowel infarction, with a smaller number succumbing to either sepsis or circulatory collapse. Concomitant administration of ephedrine or indomethacin to suppress prostaglandin E1's splanchnic vasodilatory activity did not cause any increase in mortality. A trial of aspirin, to simulate PGE's antiplatelet actions, showed no reduction in mortality when compared with detorsion alone. Prostaglandin E1 and, to a lesser extent, ibuprofen, appear to have cytoprotective effects during reperfusion of bowel compromised by volvulus, independent of their influence on the mesenteric vasculature and thrombogenesis.

Serum creatine kinase and alkaline phosphatase in experimental small bowel infarction

Serum creatine phosphokinase (CK) and alkaline phosphatase (ALP) rise after mesenteric infarction; it is not known which one rises earlier or which one has the greater elevation. This experiment compared and contrasted the elevations in both these enzyme systems after acute small bowel infarction. Isoenzymes of both systems were analyzed to determine if any qualitative changes occurred. After baseline blood samples had been drawn, 10 dogs had midline laparotomies under general anesthesia. Each was assigned to one of two groups according to a randomized block design. Controls (CON) were closed after exploration ( N = 5). The infarction (INF) group had ligation and division of the arteries to the jejunum and ileum ( N = 5). Blood samples were obtained from both groups at 3, 6, 9, 12, 24, and 27 hr after surgery. Sera were analyzed for total CK and ALP activity by automated spectrophotometry. Isoenzymes were determined by agarose gel electrophoresis. Serum CK rose faster and to a higher level than ALP after small bowel infarction (470 ± 181 vs 196 + 28 IU/liter). CK-BB was a better marker of small bowel necrosis than was intestinal ALP. The elevation of both CK and ALP by 12 hr after infarction may be a diagnostic aid if similar changes occur in humans.

Experimental small bowel obstruction. Ultrastructural observations on liver and adrenal cortical function.

In experimental small bowel obstruction an increased proportion of smooth endoplasmic reticulum and an increased number of lysosomes were seen in many liver cells. The occurrence of cytoplasmic vacuoles as well as the glycogen depletion were not pathognomonic and in the toxic pathogenesis the ultrastructural damage in the liver was only of a low degree and can be explained as a reactive (e.g. detoxication) phenomenon. The increase of plasma corticosterone content (stress reaction) differed only slightly from that of the controls, but a severe disturbance of fluid balance (increase of hematocrit and decrease of serum Na+ and C1-) and circulation failure were the more conspicuous findings, compared to toxic liver cell disturbance in the pathogenesis of small bowel obstruction.

Biochemical changes in intestinal mucosa after experimental small bowel by-pass in the rat.

1. After experimental small bowel by-pass the excluded segment of intestine, whether jejunum or ileum, shows a decrease (expressed in units/cm of intestine) in mucosal weight, protein, RNA and activity of all eight enzymes studied (leucyl β-naphthylamidase, alkaline phosphatase, β-galactosidase, α-glucosidase, aryl sulphatase, β-glucuronidase, cytochrome oxidase and catalase). There is a fall in DNA content and there are no consistent changes in enzyme activity when expressed as units/mg of DNA. 2. The intestine remaining in continuity after small bowel by-pass shows an increase (expressed in units/cm of intestine) in mucosal weight, protein, RNA and enzyme activity. There is an accompanying rise in DNA content in the intestine in continuity. 3. The increased values of all variables measured in the intestine in continuity are much more marked in ileum than in jejunum. 4. The adaptive changes seen in the by-passed intestine and the intestine in continuity are a result of ‘hypoplasia’ and ‘hyperplasia’ respectively.