Rat Model Of Postoperative Ileus Research Articles

The role of beta-adrenoreceptors in postoperative ileus in rats

The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor.

Ameliorating Effects of Electroacupuncture on Dysmotility, Inflammation, and Pain Mediated via the Autonomic Mechanism in a Rat Model of Postoperative Ileus.

Background/AimsPostoperative ileus increases healthcare costs and reduces the postoperative quality of life (QOL). The aim of this study is to investigate effects and mechanisms of electroacupuncture (EA) at ST36 and PC6 on gastrointestinal motility in rat model of postoperative ileus.MethodsLaparotomy was performed in 24 rats (control [n = 8], sham-EA [n = 8], and EA [n = 8]) for the implantation of electrodes in the stomach and mid-jejunum for recording of gastric and small intestinal slow waves. Electrodes were placed in the chest skin for electrocardiogram (ECG). Intestinal manipulation (IM) was performed in Sham-EA and EA rats after surgical procedures. Small intestinal transit (SIT), gastric emptying (GE), postoperative pain, and plasma TNF-α were evaluated in all rats.Results(1) Compared with sham-EA, EA accelerated both SIT (P < 0.05) and GE (P < 0.05) and improved regularity of small intestinal slow waves. (2) Compared with the control rats (no IM), IM suppressed vagal activity and increased sympathovagal ratio assessed by the spectral analysis of heart rate variability from ECG, which were significantly prevented by EA. (3) EA significantly reduced pain score at 120 minutes (P < 0.05, vs 15 minutes) after the surgery, which was not seen with sham-EA. (4) Plasma TNF-α was increased by IM (P = 0.02) but suppressed by EA (P = 0.04) but not sham-EA.ConclusionThe postoperative ileus induced by IM, EA at ST36 and PC6 exerts a prokinetic effect on SIT and GE, a regulatory effect on small intestinal slow waves and an analgesic effect on postoperative pain possibly mediated via the autonomic-cytokine mechanisms.

Acupuncture protects the interstitial cells of Cajal by regulating miR-222 in a rat model of post-operative ileus.

Recovery of the interstitial cells of Cajal (ICCs) during post-operative ileus (POI) is important for the restoration of gastrointestinal (GI) motility. Acupuncture can protect ICCs, but the underlying mechanisms remain unclear. In this study, we investigated whether miR-222, c-kit and endothelial nitric oxide synthase (eNOS) are involved in the putative effects of acupuncture on ICC recovery. A POI model was established in Sprague-Dawley rats by colo-colic anastomosis, and then acupuncture was performed at bilateral ST36, SP6 and LR3 once daily for 3 consecutive days. C-kit protein expression in the colonic tissue adjacent to the incision site was determined by immunohistochemistry and Western blotting. mRNA levels of c-kit, eNOS and miR-222 were measured by real-time polymerase chain reaction (RT-PCR). The levels of c-kit mRNA/protein and eNOS mRNA decreased, while miR-222 increased in the colonic tissues of POI model rats. Acupuncture treatment improved GI motility, inhibited the up-regulation of miR-222 and blocked the down-regulation of c-kit mRNA/protein and eNOS mRNA. The levels of miR-222 and c-kit were negatively correlated. Acupuncture at ST36, SP6 and LR3 facilitates ICC recovery and improves post-operative GI motility in part through regulation of miR-222, c-kit and eNOS.

Effect of DA-9701, a Novel Prokinetic Agent, on Post-operative Ileus in Rats.

Background/AimsPost-operative ileus (POI) is a common complication of abdominal surgery. DA-9701, an extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that also alleviates visceral pain. The aim of this study was to investigate whether DA-9701 can ameliorate POI in rats.MethodsA total of 32 rats were divided into 4 groups: no surgery/no medication (NSNM), no surgery/medication (NSM), surgery/no medication (SNM), and surgery/medication (SM). Gastrointestinal transit (GIT), which is assessed by migration of charcoal, and cumulative stool weight were measured at 24 hours after surgery.ResultsGIT was significantly more delayed in the SNM group than in the other groups (SNM vs NSNM, P < 0.001; SNM vs NSM, P < 0.001; SNM vs SM, P = 0.005). Cumulative stool weight in that group was also lower than in the no surgery groups (SNM vs NSNM, P = 0.007; SNM vs NSM, P = 0.033), and there was no significant difference between the SM group and the no surgery groups (SM vs NSM, P = 0.703; SM vs NSNM, P = 0.347).ConclusionDA-9701 can ameliorate POI by reducing delayed GIT and improving defecation in a rat model of POI.

Anti-inflammatory effect of ginsenoside Rb1 contributes to the recovery of gastrointestinal motility in the rat model of postoperative ileus.

Ginsenoside Rb1 (GRb1), one of the principle active components of Panax ginseng, has been reported to reduce inflammation in various diseases. In the present study, we investigated whether GRb1 has an anti-inflammatory effect on postoperative ileus (POI) and further contributes to the recovery of gastrointestinal motility. POI was induced in rats by intestinal manipulation. The POI rats received 5, 10 and 20 mg/kg GRb1 orally via gavage four times before and after surgery. Gastrointestinal motility was assessed by charcoal transport. Systemic inflammation was assessed by serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 concentrations, whereas intestinal inflammation was assessed by the activity of myeloperoxidase, and concentrations and gene expression of TNF-α, IL-1β, IL-6 and IL-10 in the ileum tissue. The results revealed that GRb1 increased rat gastrointestinal transit with POI. The increased levels of systemic and intestinal inflammatory parameters in POI rats were also reduced by GRb1. In addition, GRb1 reduced systemic and intestinal inflammation and increased the gastrointestinal transit of POI rats in a dose-dependent manner, and with significance at doses of 10 and 20 mg/kg. These results suggest that GRb1 has a potent anti-inflammatory effect on POI and further contributes to the recovery of gastrointestinal motility. GRb1 may be a promising treatment for POI prophylaxis.

Effect of spinal cord stimulation in a rodent model of post‐operative ileus

Post-operative ileus (POI) is a transient impairment of gastrointestinal (GI) transit that develops after abdominal surgery. The goal of this study was to investigate the effect of spinal cord stimulation (SCS) on gastric emptying and upper GI transit in a rat model of POI. All rats had an electrode placed on the dorsal surface of the spinal cord between the T(5) and T(8) segments. After recovery, gastric emptying and upper GI transit (geometric centre and head of meal) were assessed using a radiolabelled meal fed to each rat via oral gavage. In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz, 0.2 ms at 90% motor threshold for 15 min) was performed immediately after the meal. The sham control group had no current applied. The naïve group was without POI or SCS. Gastric emptying was significantly delayed in sham-stimulated rats with POI compared with naïve controls (39.8 +/- 6.2%vs 76.5 +/- 4.9%, P < 0.001). In rats with POI that underwent SCS, there was a significant acceleration of gastric emptying to levels that resembled those of naïve controls (65.1 +/- 7.4%, P < 0.05). However, while SCS did not normalize the geometric centre and head of the meal when compared with the naïve group, it did significantly improve both parameters compared with the sham stimulation group. In summary, SCS normalizes gastric emptying and improves upper GI transit in a rodent model of POI. Further experiments are required to address the mechanism(s) by which SCS exhibits prokinetic activity.

716 Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rat Model of Postoperative Ileus

716 Efficacy of Ipamorelin, a Novel Ghrelin Mimetic, in a Rat Model of Postoperative Ileus

Lipid-Rich Enteral Nutrition Reduces Postoperative Ileus in Rats via Activation of Cholecystokinin-Receptors

This study investigates the effect of lipid-rich nutrition on the local inflammatory response and gastrointestinal hypomotility in a rat model of postoperative ileus. Postoperative ileus is a major clinical problem, in which inflammation of the intestinal muscularis plays a key pathogenic event. Previously, administration of lipid-rich nutrition has been shown to reduce inflammation by activation of the autonomic nervous system via cholecystokinin-receptors. Postoperative ileus was induced by manipulation of the small intestine in rats. Peritoneal lavage fluid, plasma, and jejunal segments were collected at several time points to determine inflammatory mediators in fasted rats and rats fed a lipid-rich or control nutrition. Gastrointestinal transit was measured 24 hours after surgery. Administration of lipid-rich nutrition markedly reduced the manipulation-induced local inflammatory response compared to rats treated with control nutrition. The intervention with lipid-rich nutrition significantly reduced plasma levels of rat mast cell protease-II (P < 0.05) and peritoneal levels of tumor necrosis factor-alpha (P < 0.01) and interleukin-6 (P < 0.05). Furthermore, the influx of neutrophils, expressed as tissue level myeloperoxidase was significantly prevented by lipid-rich nutrition (P < 0.05). Above all administration of lipid-rich enteral nutrition resulted in a significant improvement of gastrointestinal transit compared to control nutrition (P < 0.05). Blocking of cholecystokinin-receptors prevented the anti-inflammatory and motility promoting effect of lipid-rich feeding. Our data demonstrate that nutritional stimulation of the autonomic nervous system with enteral lipids reduces postoperative ileus by inhibition of inflammation. Clinically, lipid-rich enteral nutrition may be a new therapeutic option in the treatment of postoperative ileus.

Effect of the ghrelin receptor agonist TZP-101 on colonic transit in a rat model of postoperative ileus

Ghrelin, the natural ligand of the growth hormone secretagogue receptor (ghrelin receptor), is an orexigenic gut hormone with prokinetic action in the upper gastrointestinal tract. Previously we have shown in a rodent model of postoperative ileus that the synthetic ghrelin receptor agonist TZP-101 prevents the delay in gastric emptying and improves small intestinal transit. The goal of the present study was to investigate whether TZP-101 affects colonic transit and food intake in rats with postoperative ileus. Fasted rats were treated with morphine and subjected to laparotomy under isoflurane anesthesia. Following surgery the animals were placed in clean home cages and fecal pellet output and food intake were monitored for 48 h. TZP-101 or vehicle were administered as 3 i.v. bolus infusions at 0 h, 2 h and 4 h post-surgery. TZP-101 (0.03–1 mg/kg) dose-dependently decreased the time to first bowel movement and increased fecal pellet output measured at 12 h and 24 h post-surgery compared to the vehicle. The administration of TZP-101 was not associated with a significant alteration in food intake. In conclusion, this study provides the first experimental evidence that a novel ghrelin receptor agonist improves large bowel function in rats with postoperative ileus, suggesting that TZP-101 may be useful in the clinic to accelerate upper gastrointestinal transit and to shorten the time to the first bowel movement following surgery.

Prokinetic Effects of a New Ghrelin Receptor Agonist TZP-101 in a Rat Model of Postoperative Ileus

Postoperative ileus (POI) is a major cause of postoperative complications and prolonged hospitalization. Ghrelin, which is the endogenous ligand for the growth hormone secretagogue receptor, has been found to stimulate gastric motility and accelerate gastric emptying. The present study investigates whether TZP-101 (0.03-1 mg/kg i.v.), a synthetic ghrelin-receptor agonist, could improve gastrointestinal transit in rats with POI. Since the main factors for the development of POI are the surgical manipulation and the gastrointestinal effects of opioid-receptor agonists used for pain management, the effect of TZP-101 was investigated in rats subjected to surgery, to morphine treatment (3 mg/kg s.c.), or to a combination of both. The results showed that TZP-101 is equally effective against the delayed gastrointestinal transit induced by surgery, by morphine, or by the combination of both interventions. The prokinetic action of TZP-101 was more pronounced in the stomach compared to the small intestine.

Salutary Effects of Tachykinin Receptor Antagonists in a Rat Model of Postoperative Ileus

Postoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK(1-3) antagonists, SR140333, SR48968, and SR142801, was investigated. Intestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats. Diethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals--UN: 61.17 +/- 5.47, 62.10 +/- 8.30, and 56.70 +/- 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 +/- 2.07 and 9.70 +/- 1.15 cm, respectively. SR140333 (3-30 microg/kg), SR48968 (1-30 microg/kg), and SR142801 (3-10 microg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 +/- 1.08, 21.70 +/- 0.19, and 25.0 +/- 1.34 cm. The combinations of submaximal doses of NK(1) and NK(3), NK(2) and NK(3) and NK(1), and NK(2) and NK(3) antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK(1) + NK(2) antagonists) acted additively, the intestinal transit reaching 26.60 +/- 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP. SR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK(1) and NK(2) antagonists being most beneficial.

Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats

BACKGROUND/AIMThe effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with...

Effects of mu- and kappa-opioid receptors on postoperative ileus in rats.

In a rat model of postoperative ileus, induced by abdominal surgery, we investigated the effect of mu- and kappa-opioid receptors. Different degrees of inhibition of the gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy or laparotomy plus manipulation of the gut. Morphine (1 mg/kg), a preferential mu-opioid receptor agonist, significantly inhibited the transit after skin incision, while the transit after the laparotomy with or without manipulation was not significantly affected. Fedotozine (5 mg/kg), a peripheral kappa-opioid receptor agonist, enhanced the transit after laparotomy plus manipulation, while naloxone (1 mg/kg), a non-specific opioid receptor antagonist, further inhibited the transit after laparotomy plus manipulation. Naloxone and fedotozine alone had no effect on the transit after skin incision or laparotomy without manipulation. However, naloxone prevented the effect of morphine on the transit after skin incision and of fedotozine on the laparotomy plus manipulation. These results support a role for peripheral kappa-opioid receptors in the pathogenesis of postoperative ileus induced by abdominal surgery.

Ketorolac Prevents Postoperative Small Intestinal Ileus in Rats

The effect of ketorolac, a parenterally administered, nonsteroidal anti-inflammatory drug, was examined in a rat model of postoperative ileus. Small intestinal transit was measured by calculating the geometric center (GC) of distribution of 51 CrO 4 . Laparotomy significantly delayed transit (GC: 2.2 ±0.2 after laparotomy versus 5.6±0.5 for unoperated controls, p

Ketorolac prevents postoperative small intestinal ileus in rats

The effect of ketorolac, a parenterally administered, nonsteroidal anti-inflammatory drug, was examined in a rat model of postoperative ileus. Small intestinal transit was measured by calculating the geometric center (GC) of distribution of 51CrO4. Laparotomy significantly delayed transit (GC: 2.2 +/- 0.2 after laparotomy versus 5.6 +/- 0.5 for unoperated controls, p < 0.01). The administration of ketorolac (1 mg/kg) improved the GC to 5.2 +/- 0.2 (p < 0.01), indicating normal intestinal transit after surgery in ketorolac-treated animals. Small intestinal myoelectric activity was recorded in rats with implanted electrodes. Animals treated with saline 2 hours postoperatively did not show return of the migrating myoelectric complex (MMC) in 183 +/- 25 minutes. In contrast, rats receiving ketorolac postoperatively had return of MMC activity in 59 +/- 18 minutes (p < 0.01). Preoperative ketorolac treatment reduced the duration of MMC inhibition after surgery from 197 +/- 55 minutes to 13 +/- 5 minutes (p < 0.05) when compared with saline. In summary, ketorolac hastens the return of MMC activity when given postoperatively. When ketorolac is administered preoperatively, it completely prevents the delay in intestinal transit and the inhibition of myoelectric activity seen in postoperative ileus. We concluded that ketorolac may be of benefit in the prevention and treatment of postoperative ileus.