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Laparotomy involving manipulation of the small intestine causes injury, initiating an inflammatory cascade in the small bowel wall, which generates eicosanoids and proinflammatory cytokines. We have shown that ketorolac and salsalate, nonselective cyclooxygenase (COX) inhibitors, ameliorate postoperative small bowel ileus in a rodent model. Others have shown that interleukin-1 receptor antagonism improves postoperative gastric emptying. We examined whether inhibition of the proinflammatory cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1), or selective blockade of cyclooxygenase-2 (COX-2), the COX isoform induced during inflammation, would accelerate postoperative small bowel transit in our model. Duodenostomy tubes were inserted into male Sprague-Dawley rats. One week later, animals were randomized to receive TNF-binding protein (TNF-bp), IL-1 receptor antagonist (IL-1ra), or saline (NS) prior to standardized laparotomy. Additional rats were gavaged preoperatively with a selective COX-2 inhibitor (NS-398) or NS. Small intestinal transit was measured as the geometric center (GC) of distribution of (51)CrO(4) at 30 min, 3 h, or 6 h (n = 5-9 rats/group) following laparotomy. Selective inhibition of COX-2 significantly increased postoperative small bowel transit compared to controls (GC 2.9 +/- 0.3 vs 2.2 +/- 0.1 at 30 min, GC 2.9 +/- 0.3 vs 2.5 +/- 0.2 at 3 h, and GC 3.3 +/- 0.3 vs 2.8 +/- 0.2 at 6 h, P < 0.05). In contrast, neither TNF-bp nor IL-1ra altered postoperative small intestinal transit in this model. Use of selective COX-2 inhibitors may accelerate recovery of postoperative bowel dysmotility without the undesirable effects (e.g., gastrointestinal irritation and anti-platelet effect) of nonselective COX inhibitors., (Copyright 1999 Academic Press.)

Octreotide, a somatostatin analogue that inhibits the release of most gut peptides, hastens the resolution of experimental postoperative ileus, suggesting that gut peptides mediate this process. We studied the role of two gut peptides involved in the control of normal gut motility, vasoactive intestinal peptide (VIP), and substance P (SP), in the initiation and maintenance of postoperative small bowel ileus in rats by preoperative administration of VIP and SP receptor antagonists, (VIP-ra and SP-ra). Thirty male Sprague-Dawley rats (300-350 g) underwent laparotomy. One half underwent placement of a duodenal catheter for transit studies while the other half had serosal electrodes placed on the proximal jejunum for myoelectric recordings. Six days later, animals were separated into three treatment groups of five each. Control animals were pretreated with ip saline, while the others received either VIP-ra or SP-ra prior to standardized laparotomy. Following abdominal closure, [Na51]CrO4 was injected into the duodenum and the animals were sacrificed 25 min later. The small bowel was then excised and divided into 10 equal segments. Small bowel transit was calculated as the geometric center of [Na51]CrO4 distribution. The interval until the return of migrating myoelectric complexes (MMCs) was determined in animals with intestinal electrodes. VIP-ra-treated rats demonstrated a 67% improvement in the geometric center of radiolabel relative to controls and SP-ra-treated rats had a 23% improvement (3.67 +/- 0.06 VIP-ra vs 2.69 +/- 0.09 SP-ra vs 2.20 +/- 0.09 control, P < 0.01). MMCs returned 180 +/- 17 min in controls vs 99 +/- 14 min in VIP-ra-treated rats (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed gastric emptying and altered upper gut transit or both are common following Roux-en-Y gastrojejunostomy and are thought to be due to altered efferent limb transit secondary to isolation of the Roux limb from the duodenal pacemaker. We postulated that preservation of myoneural continuity of the Roux limb with the duodenal pacemaker would enhance solid gastric emptying, while division of the afferent limb of a Billroth II gastrojejunostomy (B-II), isolating the efferent jejunal limb from the duodenal pacemaker, would slow gastric emptying. Solid gastric emptying was measured in 14 dogs, who then underwent gastric vagotomy and antrectomy. Eight animals were reconstructed with a Roux-en-Y gastrojejunostomy, preserving myoneural but not luminal continuity of the Roux limb with the afferent limb via a muscularis bridge, while six dogs underwent standard B-II gastrojejunostomy. Serosal electrodes were placed on the afferent and efferent jejunal limbs. Gastric emptying was restudied, with fed and fasted myoelectric recordings. The bridge was then divided to create a standard Roux, while the afferent limb was transected and reanastomosed just proximal to the gastrojejunostomy in the B-II dogs to isolate the efferent limb from the duodenal pacemaker, with repeat studies. Bridge dogs had delayed solid gastric emptying compared to their preoperative state, despite normal efferent limb motility.(ABSTRACT TRUNCATED AT 250 WORDS)

We have demonstrated that erythromycin improves gastric emptying in dogs following truncal vagotomy and Roux-en-Y antrectomy (VRYA). To explore its mechanism of action we studied gastric emptying and myoelectric activity in a canine Roux model and administered atropine simultaneously with erythromycin. Tachyphylaxis was evaluated following short-term administration. Four dogs with delayed gastric emptying following VRYA were studied. Radionuclide solid gastric emptying was measured, with simultaneous myoelectric recordings obtained from the duodenum and Roux limb. Study groups were: (1) saline control (VRYA dogs); (2) erythromycin 1 mg/kg iv over 1 hr; (3) erythromycin 3 mg/kg po tid for 1 week, with repeat studies using erythromycin 1 mg/kg iv over 1 hr; and (4) atropine 0.5 mg/kg iv bolus, followed by a 1-hr infusion of atropine 0.05 mg/kg and erythromycin 1 mg/kg. Control Roux animals had severe gastric retention (73 +/- 5% at 2 hr, compared to 27 +/- 6% following iv erythromycin (P less than 0.01). Clustered spike bursts were observed in the Roux limb following erythromycin. Atropine abolished the gastrokinetic response and suppressed the myoelectric response to erythromycin (81 +/- 3% retention at 2 hr, P less than 0.01 compared to erythromycin alone). The response to erythromycin was unchanged after 1 week of tid administration (40 +/- 14% retention at 2 hr postprandial, P = NS). Erythromycin improves gastric emptying in VRYA dogs via a cholinergic pathway and does not exhibit tachyphylaxis following short-term administration.

The purpose of this study was to compare gastric emptying and Roux myoelectric activity in a canine model. Four dogs underwent truncal vagotomy, antrectomy, and 40 cm Roux-en-Y gastrojejunostomy, with placement of serosal electrodes. Following recovery, gastric emptying was determined scintigraphically with a radiolabeled solid meal, and fasting and fed small-bowel myoelectric activity was obtained. Gastric emptying was markedly slowed compared to control unoperated animals (202 +/- 91 versus 46 +/- 12 min; P less than 0.05). Slow wave frequency declined in the Roux limb compared to the duodenum (14.2 +/- 0.4 versus 18.0 +/- .06 counts per minute; P less than 0.01). No gradient in slow wave frequency was observed in the Roux limb, although one animal was noted to have reversed propagation of slow waves in the proximal Roux limb. Migrating myoelectric complexes (MMCs) were coordinated between the Roux limb and jejunum distal to the enteroenterostomy, but not with the duodenum. Periodicity of the MMCs was different in the Roux limb and duodenum (98.6 +/- 6.3 versus 138 +/- 17.5 min; P less than 0.05). None of the animals converted to the fed myoelectric pattern with a 272 kcal meal (MMC periodicity in the Roux limb = 99 +/- 10 min postprandially, P = N.S.). These quantitative and qualitative alterations in myoelectric activity may contribute to the observed delay in gastric emptying following Roux-en-Y gastrojejunostomy.