Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats.

BACKGROUND: Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine-derived SIS. METHODS: Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). RESULTS: The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. CONCLUSIONS: This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation.

Pediatric intestinal failure: Predictors of metabolic bone disease.

PURPOSE: The purpose of this study was to identify risk factors for the development of metabolic bone disease (MBD) in pediatric intestinal failure (IF). METHODS: A retrospective single-center study of 36 pediatric IF patients who were screened for MBD was performed. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Simple regression analysis was initially performed to screen predictors, followed by multivariate step-wise linear regression analysis to identify risk factors of MBD. RESULTS: Mean lumbar spine BMD Z-score was -1.16 ± 1.32, and 50.0% of patients had a BMD Z-score less than -1.0. Deficiency of 25-hydroxyvitamin-D (25-OHD <30 ng/ml) was present in the 63.8% of patients, while 25.0% had hyperparathyroidism (intact parathyroid hormone (PTH)>55 pg/ml). Seven patients (19.4%) had bone pain, of which 4 (11.1%) suffered a pathologic fracture. Using multivariate analysis, parenteral nutrition (PN) duration predicted decreased BMD (B=-0.132, p=0.006). Serum 25-OHD nonsignificantly correlated with BMD Z-score (B=0.024, p=0.092). Interestingly, repeat DXA after increasing vitamin D supplementation showed no improvement in BMD Z-score (-1.18 ± 1.49 vs -1.36 ± 1.47, p=0.199). CONCLUSIONS: Pediatric IF is associated with a significant risk of MBD, which is predicted by the duration of PN-dependence. These findings underscore the importance of BMD monitoring. Better therapies for treating IF-associated MBD are needed.

Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing.

High-risk anastomoses in the gut may benefit from the application of a synthetic reinforcement to prevent an enteric leak. Recently a porcine-derived small intestine submucosa (SIS) was tested as a bioscaffold in a number of organ systems. The aim of this study was to evaluate the effectiveness of SIS in stimulating healing in the stomach. Twelve rats underwent surgical removal of a full-thickness gastric defect (1 cm) and subsequent repair with a double-layer patch of porcine-derived SIS. The graft was secured with interrupted sutures placed within 1 mm of the edge of the graft. After 21 days, the animals were killed and their stomachs harvested for histologic examination. Cross sections were processed for paraffin embedding and 4-micron sections were stained with hematoxylin and eosin. All animals survived, gained weight, and demonstrated no signs of peritonitis over the 3-week postoperative period. On postmortem examination, the defect was completely closed in all animals by granulation tissue and early fibrosis. Although most of the luminal surface of the grafted areas remained ulcerated, early regeneration of normal gastric mucosa was seen at the periphery of the defect. SIS may act as an effective scaffolding agent for intestinal mucosa and may offer protection in high-risk anastomoses.

Role of vagus nerve in postprandial antropyloric coordination in conscious dogs.

It is generally believed that gastric emptying of solids is regulated by a coordinated motor pattern between the antrum and pylorus. We studied the role of the vagus nerve in mediating postprandial coordination between the antrum and pylorus. Force transducers were implanted on the serosal surface of the body, antrum, pylorus, and duodenum in seven dogs. Dogs were given either a solid or a liquid meal, and gastroduodenal motility was recorded over 10 h. Gastric emptying was evaluated with radiopaque markers mixed with a solid meal. Dogs were treated with hexamethonium, N(G)-nitro-l-arginine methyl ester (l-NAME), or transient vagal nerve blockade by cooling. A postprandial motility pattern showed three distinct phases: early, intermediate, and late. In the late phase, profound pyloric relaxations predominantly synchronized with giant antral contractions that were defined as postprandial antropyloric coordination. A gastric emptying study revealed that the time at which gastric contents entered into the duodenum occurred concomitantly with antropyloric coordination. Treatment by vagal blockade or hexamethonium significantly reduced postprandial antral contractions and pyloric relaxations of the late phase. l-NAME changed pyloric motor patterns from relaxation dominant to contraction dominant. Solid gastric emptying was significantly attenuated by treatment with hexamethonium, l-NAME, and vagal blockade. Postprandial antropyloric coordination was not seen after feeding a liquid meal. It is concluded that postprandial antropyloric coordination plays an important role to regulate gastric emptying of a solid food. Postprandial antropyloric coordination is regulated by the vagus nerve and nitrergic neurons in conscious dogs.

Celecoxib (celebrex) increases canine lower esophageal sphincter pressure.

BACKGROUND: Prostaglandins inhibit the contraction of gastrointestinal smooth muscle and may decrease lower esophageal sphincter tone. The purpose of this study was to determine whether the cyclooxygenase-2 inhibitor celecoxib (Celebrex) could increase lower esophageal pressure (without affecting gastric emptying) compared to placebo and cisapride (Prepulsid), a compound previously used to treat reflux disease. MATERIALS AND METHODS: Six mongrel dogs were assigned to receive celecoxib, cisapride, and placebo using a randomized cross-over design with a 1-week washout period between treatments. Prior to dosing, each dog underwent an esophagopexy to provide access to the esophagus and stomach. On the fourth day of dosing, sphincter tone was measured in awake unsedated dogs using radial manometry. In a different set of six dogs, liquid and solid gastric emptying rates were scintigraphically determined. RESULTS: Celecoxib significantly increased mean and average maximum lower esophageal pressures compared to placebo without affecting the gastric emptying rate. The magnitudes of these increases were similar to that produced by cisapride. CONCLUSIONS: Celecoxib had a positive effect on canine lower esophageal sphincter tone. This finding, combined with the drug's low incidence of gastrointestinal toxicity, suggests that celecoxib may warrant consideration and investigation as a pharmacotherapy for human reflux disease.