Increased risk for complications after colorectal surgery with selective cyclo-oxygenase 2 inhibitor etoricoxib.

BACKGROUND: Cyclo-oxygenase 2 inhibitors can be used for pain treatment after colorectal surgery. OBJECTIVE: The aim of this study was to investigate whether the use of etoricoxib has negative effects on the perioperative outcome in colorectal surgery. DESIGN: Complication data from an advanced medical database system were sampled prospectively, and patient records were reviewed retrospectively. PATIENTS: All patients with elective colorectal surgery within an enhanced recovery after surgery protocol from 2008 to 2009 were selected. INTERVENTION: The nonrandomized use of perioperative etoricoxib treatment was compared with a control group. MAIN OUTCOME MEASURES: The primary outcome measured was the number of patients with postoperative complications according to the Dindo-Clavien classification. RESULTS: One hundred one patients received etoricoxib treatment, whereas 104 did not. The patient groups were very comparable. We observed a significant increase in the number of patients with postoperative complications with etoricoxib treatment (43 vs 30 patients; 42.6% vs 28.8%, p = 0.041) due to an increase in patients with a major complication (Dindo-Clavien complication grade III-V: 22.8% vs 9.6%, p = 0.01). Patients with etoricoxib treatment and a complication needed a longer recovery period than patients with a complication in the control group (18 (17; 20) vs 14 (13; 15) days, p = 0.05). We observed an increased level of postoperative serum creatinine with etoricoxib treatment (105 (98; 112) vs 82 (78; 85), p = 0.003), which was more pronounced in patients with a complication (141 (127; 155) vs 91 (83; 98), p = 0.002; 25 vs 8 patients with serum creatinine >100 µmol/L, p = 0.008). In multivariate analysis, etoricoxib was identified as an independent risk factor for experiencing a major complication with a risk increase of approximately 2.5-fold (p = 0.03). LIMITATIONS: This study was limited by the nonrandomized use of perioperative etoricoxib and the retrospective nature of its review of patient records. CONCLUSIONS: Etoricoxib increased the number of patients with postoperative complications and should be considered carefully in colorectal surgery.

Cholecystokinin-58 is more potent in inhibiting food intake than cholecystokinin-8 in rats.

INTRODUCTION: Several cholecystokinin (CCK) forms have been detected in plasma, but most studies on food intake investigated the effects of CCK-8 only. Recently, it has been demonstrated that CCK-58 is the only endocrine-active form of CCK in rats. METHODS: CCK-58 was synthesized with a peptide synthesizer using FMOC chemistry and CCK-58 effects on food intake were compared to CCK-8 in rats. RESULTS: Both CCK-58 and CCK-8 inhibited food intake in a dose-dependent manner and were equally potent at 30 min. CCK-58 showed a prolonged inhibition of food intake compared to CCK8 at the higher dose tested (7 nmol/kg), inhibiting food intake also at 60 min, and cumulative food intake was inhibited for up to 210 min by CCK-58. CONCLUSIONS: CCK-58 has the same potency in inhibiting food intake as CCK-8 in rats, but inhibits food intake longer. This might be due to its tertiary structure resulting in a delayed plasma degradation or a prolonged binding at the CCK receptor. As CCK-58 is the major CCK form in the gut wall and possibly in the circulating blood in humans, the effects of CCK on food intake might have been underestimated in the past.

Postoperative colonic motility after tropisetron and a standardized meal in patients undergoing conventional colorectal surgery.

BACKGROUND: Early postoperative enteral nutrition is advantageous for the recovery of colonic motility but may be limited by abdominal distension, nausea, and vomiting. We aimed to investigate the tolerance of a standardized meal after pretreatment with the 5-hydroxytryptamine-3-receptor antagonist tropisetron and to study the concomitant colonic motility. METHODS: Colonic motility and tone were recorded on postoperative day 1 to 3 with a combined manometry/barostat recording catheter in 12 patients who underwent open colorectal surgery with an anastomosis in the distal colon or rectum. The study protocol consisted of 30 min of baseline recordings followed by 5 mg of tropisetron intravenously. Then, motility was recorded for another 30 min before patients ingested a standardized meal to trigger the gastrocolonic response. Postprandial motility was recorded for the subsequent 60 min. RESULTS: The colonic motility index increased after administration of tropisetron on all three postoperative days (day 1: 34+/-11 vs 122+/-48, day 2: 55+/-19 vs 101+/-25, and day 3: 42+/-16 vs 93+/-33 mmHg/min; p<0.05). No further increase of the motility index was observed postprandially. Frequency and amplitude of contractions were virtually unaffected by tropisetron and the meal. Barostat bag volume decreased postprandially in the proximal bag on the third, and in the distal bag on the first and second postoperative day (p<0.05). Patients' condition was unaffected by the standardized meal after tropisetron administration. CONCLUSIONS: Tropisetron may enhance colonic motility in the early postoperative period; however, the gastrocolonic response was impaired thereafter. High caloric food intake is well tolerated early after surgery after tropisetron pretreatment.

TGF-beta3 inhibits pentagastrin-stimulated gastric acid secretion in rats.

BACKGROUND: Transforming growth factor beta3 (TGF-beta3) has been shown to accelerate gastric ulcer healing in rats. However, little is known about the mechanism. In this study we investigated the influence of TGF-beta3 on gastric acid secretion, since gastric hyperacidity is a major cause of gastroduodenal ulcer disease. MATERIAL/METHODS: Male Sprague Dawley rats were equipped with gastric Thomas cannulas and jugular vein catheters. The acute effect of either intravenous TGF-beta3 (400 and 1200 pg/kg/h) or saline (0.15 M) on pentagastrin-stimulated (10 pg/kg/h) gastric acid secretion was evaluated by gastric acid back-titration after 5 days of recovery. Additionally, pentagastrin-stimulated gastric acid secretion was assessed after 48 hours following TGF-beta3 (1200 microg/kg/h) or saline treatment. RESULTS: Pentagastrin significantly increased gastric acid production. TGF-beta3 significantly reduced pentagastrin-stimulated gastric acid secretion in a dose-dependent manner as early as 15 minutes after application (saline: 124.9+/-14.9 microEq H+/15 min, TGF-beta3: 97.7+/-13.1 9 microEq H+/15 min, p<0.002). Additionally, pretreatment with TGF-beta3 abolished the effect of pentagastrin on gastric acid production. This effect lasted throughout the entire recording period of 48 hours. However, baseline physiological gastric acid production was not altered by TGF-beta3. CONCLUSIONS: TGF-beta3 inhibits gastric acid secretion when given prior to as well as after pentagastrin treatment. This implicates both a preventive and a therapeutic role of TGF-beta3 in gastroduodenal ulcer disease.

Postoperative colonic motility increases after early food intake in patients undergoing colorectal surgery.

BACKGROUND: Stimulation of colonic motility by the gastrocolonic response may help to reduce inhibition of gastrointestinal motility after colorectal surgery. We aimed to investigate whether postoperative colonic motility is increased after early food intake. METHODS: Nineteen patients undergoing colorectal surgery and 7 healthy volunteers were investigated. Colonic motility was recorded with a combined manometry/barostat system, and the effect of a standard 500-kcal meal was evaluated once in healthy volunteers and in 15 patients on the first and second postoperative day. Four patients remained unfed, serving as controls. RESULTS: In patients, the colonic motility index increased from 12 +/- 5 at baseline to 65 +/- 24 mm Hg after the meal on postoperative day 1 (mean +/- SEM; P < .01), while barostat bag volumes decreased, indicating a rise in colonic tone. On day 2, the motility index was 62 +/- 17 mm Hg at baseline and did not change after the meal. In unfed controls, no change was observed during colonic motility recordings on both postoperative days. In healthy volunteers, the colonic motility index increased from 98 +/- 52 at baseline to 151 +/- 58 mm Hg postprandially (P < .05). CONCLUSIONS: As in healthy volunteers, there is a potential to stimulate colonic motility by early food intake in postoperative patients. This may help to improve prolonged colonic motility disorders after colorectal surgery.

Mesenteric lymph collected during peritonitis or sepsis potently inhibits gastric motility in rats.

Gastrointestinal motility is strongly inhibited during peritonitis or sepsis and proinflammatory cytokines released into mesenteric lymph during an acute gastrointestinal insult mediate systemic responses. We investigated whether mesenteric lymph collected during peritonitis or sepsis inhibits gastric motility and gastric emptying. Mesenteric lymph was collected for 12 hours from three experimental groups: vehicle (saline, 1 ml, intraperitoneally [ip], control lymph), peritonitis (0.5% acetic acid, 1 ml, ip, peritonitis lymph), and sepsis (lipopolysaccharide [LPS], 5 mg/kg, 1 ml, ip, sepsis lymph). Gastric motility and gastric emptying were measured in recipient rats in response to lymph injections into the jugular vein. Quantitative polymerase chain reaction (PCR) for tumor necrosis factor alpha (TNFalpha) gene expression in the jejunum and in lymph cells were measured during sepsis. Mesenteric lymph flow significantly increased during peritonitis or sepsis (lymph flow [ml] per 60 minutes; control 2.45 +/- 0.04; peritonitis 2.67 +/- 0.07; sepsis 3.25 +/- 0.1, p < 0.01 vs. control). Injection of peritonitis or sepsis lymph (1 ml) produced a significant and prolonged inhibition of gastric motility in recipient rats (decrease in intragastric pressure and duration: control lymph -0.14 +/- 0.05 cm H(2)O, 1.89 +/- 1.31 minutes; peritonitis lymph: -0.56 +/- 0.06 cm H(2)O, 9.9 +/- 0.9 minutes; sepsis lymph: -0.51 +/- 0.05 cm H(2)O, 6.9 +/- 0.6 minutes; p < 0.001 vs. control for all comparisons). Gastric emptying was significantly inhibited by continuous infusion of sepsis lymph (3 ml per 60 minutes; gastric emptying: saline 81% +/- 4%; control lymph: 80% +/- 6%; sepsis lymph: 44% +/- 10%; p < 0.001 vs. control). TNFalpha gene expression in the gut wall of the jejunum increased during sepsis over 90-fold within the first 2 hours and decreased continuously thereafter (relative TNFalpha mRNA transcription: basal 1.0 +/- 0.05; LPS 2 hours: 91.9 +/- 2.6, p < 0.001 vs. basal; 12 hours: 24.7 +/- 16.8, not significant [NS]; 24 hours: 7.0 +/- 3.4, NS). In conclusion, mediators in mesenteric lymph, possibly cytokines, may be responsible for the inhibition of gastric motility during peritonitis or sepsis. Because the composition of mesenteric lymph probably reflects the interstitial fluid of the gut wall, monitoring visceral lymph might be an extremely beneficial tool to determine mediators released during impaired gut wall function.

Postoperative colonic motility in patients following laparoscopic-assisted and open sigmoid colectomy.

Clinical reports on laparoscopic-assisted sigmoid colectomy (LASC) suggest that the period of postoperative inhibition of gastrointestinal motility is shortened as compared to open sigmoid colectomy (OSC). We aimed to specifically investigate whether colonic motility increases more rapidly following LASC compared to OSC. LASC was performed in 11 patients and OSC in nine patients for recurrent diverticulitis or carcinoma. During surgery a manometry catheter was inserted into the colon via the anus, and the tip was placed in the splenic flexure. Continuous manometric recordings were performed from the day of surgery until postoperative day 3 with a four-channel microtransducer manometry system combined with a portable data logger. The postoperative colonic motility index was 101+/-18, 199+/-30, and 163+/-27 mm Hg/min on days 1, 2, and 3 after LASC, respectively, which was increased compared to indexes of 53+/-15, 71+/-18, and 76+/-23 following OSC (mean+/-standard error of the mean; P<0.05). The amplitude but not the frequency of contractions was higher following LASC compared to OSC. Following LASC, patients requested a similar amount of pain medication but resumed oral food more rapidly on postoperative days 2 and 3 (P<0.05), and they were discharged from the hospital earlier (P<0.05). Colonic motility in particular and the patient's condition in general seem to improve more rapidly following LASC compared to the open procedure.

Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor-mediated pathway to inhibit gastric motor function in the rat.

Nutrients in the intestine initiate changes in secretory and motor function of the gastrointestinal (GI) tract. The nature of the 'sensors' in the intestinal wall is not well characterized. Intestinal lipid stimulates the release of cholecystokinin (CCK) from mucosal entero-endocrine cells, and it is proposed that CCK activates CCK A receptors on vagal afferent nerve terminals. There is evidence that chylomicron components are involved in this lipid transduction pathway. The aim of the present study was to determine (1) the pathway mediating reflex inhibition of gastric motility and (2) activation of duodenal vagal afferents in response to chylomicrons. Mesenteric lymph was obtained from awake rats fitted with lymph fistulas during intestinal perfusion of lipid (Intralipid, 170 micromol h(-1), chylous lymph) or a dextrose and/or electrolyte solution (control lymph). Inhibition of gastric motility was measured manometrically in urethane-anaesthetized recipient rats in response to intra-arterial injection of lymph close to the upper GI tract. Chylous lymph was significantly more potent than control lymph in inhibiting gastric motility. Functional vagal deafferentation by perineural capsaicin or CCK A receptor antagonist (devazepide, 1 mg kg(-1), i.v.) significantly reduced chylous lymph-induced inhibition of gastric motility. The discharge of duodenal vagal afferent fibres was recorded from the dorsal abdominal vagus nerve in an in vitro preparation of the duodenum. Duodenal vagal afferent nerve fibre discharge was significantly increased by close-arterial injection of CCK (1-100 pmol) in 43 of 83 units tested. The discharge of 88% of CCK-responsive fibres was increased by close-arterial injection of chylous lymph; devazepide (100 microg, i.a.) abolished the afferent response to chylous lymph in 83% of these units. These data suggest that in the intestinal mucosa, chylomicrons or their products release endogenous CCK which activates CCK A receptors on vagal afferent nerve fibre terminals, which in turn initiate a vago-vagal reflex inhibition of gastric motor function.

Increased sensitivity in detection of a porcine high-turnover osteopenia after total gastrectomy by dynamic 18F-fluoride ion PET and quantitative CT.

UNLABELLED: High-resolution (18)F-fluoride ion PET in combination with quantitative CT (QCT) allows the assessment of bone metabolism in relation to bone mass. This combined imaging approach was used to elucidate porcine bone metabolic changes after gastrectomy, which are frequently associated with osteopenia or osteomalacia. METHODS: Six months after total gastrectomy (n = 7) or sham operation (n = 6), bone blood flow and bone metabolic activity (K(i), K(flux)) were calculated from dynamic PET measurements from vertebral bodies and compared with corresponding QCT bone mineral density (BMD) measurements. RESULTS: Total gastrectomy resulted in a significant reduction of the BMD (-21%; P < 0.005), whereas 1,25-(OH)(2)-vitamin D, serum phosphate, and parathyroid hormone were significantly increased compared with that of sham-operated animals. Because of the significant increase of the rate constant k(3) (+325%; P < 0.05), describing chemisorption and incorporation of (18)F-fluoride onto or into the bone matrix, K(i) (+36%) and K(flux) (+37%) were significantly elevated after total gastrectomy compared with that of control animals (P < 0.01), whereas bone blood flow was not significantly different between groups. The normalization of K(i) and K(flux) values by the specific bone mass (K(i/BMD); K(flux/BMD)) largely increased the differences between groups (K(i/BMD), +74%; K(flux), +76%; P < 0.001). CONCLUSION: Dynamic (18)F-fluoride ion PET revealed that porcine bone loss after total gastrectomy is related to a high-turnover bone disease without significant changes in bone blood flow. In mini pigs, the increased bone metabolism is probably related to an elevated parathyroid hormone secretion, thus maintaining serum calcium homeostasis at the expense of the bone mineral content. Normalizing bone metabolic activity by the specific bone mass increases the sensitivity in the detection of osteopenic high-turnover bone diseases. Therefore, the combination of QCT and (18)F-fluoride ion PET seems to be the method of choice for the classification of metabolic bone diseases and for monitoring treatment effects quantitatively.

Total gastrectomy severely alters the central regulation of food intake in rats.

OBJECTIVE: To investigate the central regulation of food intake by quantifying neuron activation of the nucleus of the solitary tract (NTS) after injection of cholecystokinin (CCK) or food intake in gastrectomized rats. SUMMARY BACKGROUND DATA: Total gastrectomy is followed by early satiety, low calorie intake, and weight loss in the majority of patients. The etiology of these effects is unknown. Sixty percent to 70% of patients remain underweight after total gastrectomy, the weight loss averaging 25% of preoperative body weight. About two thirds of gastrectomized patients report early satiety, and about 60% do not reach the recommended daily calorie intake. The NTS is a brain stem center involved in the regulation of food intake; thus, the extent and pattern of neuronal activation provide information on the process involved in the initiation of satiation and the regulation of food intake. METHODS: The authors investigated neuronal activation in the NTS using c-fos immunohistochemistry following CCK injection or food intake in healthy control rats, sham-operated control rats, age-matched control rats, weight-matched control rats, and vagotomized or gastrectomized rats. RESULTS: Neuronal activation in the NTS after CCK injection was significantly decreased 21 days after total gastrectomy, but increased by up to 51% 3 months and by up to 102% 12 months after surgery compared to age-matched unoperated control rats. Neuronal activation in the NTS in response to feeding was markedly increased up to fivefold in gastrectomized rats. This increase was early in onset and sustained, and occurred despite significantly reduced food intake. Administration of MK329, a CCK-A receptor antagonist, significantly reduced the number of postprandially activated neurons in both gastrectomized and control rats. CONCLUSIONS: The early postprandial activation of NTS neurons after total gastrectomy in rats may correspond to early satiety reported by patients, while the sustained activation of NTS neurons after a meal could contribute to a reduced daily calorie intake. These data suggest that a disturbed central regulation of food intake might contribute to early satiety, reduced food intake, and weight loss after total gastrectomy.

Serotonin receptor blockade increases food intake and body weight after total gastrectomy in rats.

BACKGROUND: Total gastrectomy often results in early satiety and loss of body weight. Serotonin inhibits food intake, and postprandial serotonin release is increased after total gastrectomy. Serotonin might contribute to early satiety and loss of body weight after total gastrectomy. METHODS AND MATERIALS: Food intake and body weight were investigated with an automated recording system in gastrectomized rats 1-12 months postoperatively. Rats were treated with metergoline, a 5-hydroxytryptamine (5-HT)(1/2) receptor antagonist, two different 5-HT(3) receptor antagonists, a combination of metergoline and devazepide, a cholecystokinin (CCK) a receptor antagonist, or vehicle. In addition, metergoline or vehicle was applied continuously by an intraperitoneal osmotic minipump for 7, 28, or 84 days after total gastrectomy. RESULTS: Metergoline treatment resulted in a dose-dependent increase in food intake in gastrectomized rats. 5-HT(3) receptor antagonist treatment had no effect, and devazepide in addition to metergoline did not further stimulate food intake. Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% (24-h cumulative food intake [FI], 6 months: vehicle 3.83 +/- 0.10, metergoline 5.52 +/- 0.15 g/100 g body weight (BW), P < 0.0001). Chronic metergoline treatment for 7, 28, or 84 days significantly increased food intake after total gastrectomy compared to vehicle treatment (FI 7 days: vehicle 30.83 +/- 0.71, metergoline 36.27 +/- 0.85 g/100 g BW; P < 0.0002; average weekly FI during 28 days; vehicle 31.23 +/- 0.22, metergoline 36.83 +/- 0.33 g/100 g BW, P < 0.0001; average weekly FI during 84 days: vehicle 33.02 +/- 0.59, metergoline 35.07 +/- 0.48 g/100g BW, P < 0.008), and there was a significant body weight increase compared to vehicle treatment (7 days: DeltaBW vehicle -0.7 +/- 1.2 g vs DeltaBW metergoline 9.0 +/- 2.1 g, P < 0.001; 28 days: DeltaBW vehicle 0.3 +/- 2.2 vs DeltaBW metergoline 13.0 +/- 2.3, P < 0.001; 84 days: DeltaBW vehicle 25.7 +/- 10.2 vs DeltaBW metergoline 49.5 +/- 7.2, P < 0.04). Treatment for 84 days resulted in a significant body weight gain, while vehicle treatment had no effect (vehicle: 438 +/- 11 g vs 464 +/- 12 g, P < 0.2, n.s.; metergoline: 448 +/- 9 g vs 498 +/- 10 g, P < 0.007). CONCLUSIONS: Inhibition of food intake by serotonin might contribute to early satiety and loss of body weight after total gastrectomy.

Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [(15)O]H(2)O and [(18)F]fluoride ion positron emission tomography.

Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [(18)F]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K(1) values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The "true" bone blood flow ( f(H2O)) was measured in vertebral bodies by dynamic [(15)O]H(2)O PET, followed by a 120-min dynamic [(18)F]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K(1) values (f) and the net uptake of fluoride in bone tissue (K(i)), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K(i) and k(3) ( P<0.05), which was mainly caused by an increase of the fraction of bound tracer in tissue (P<0.01). In contrast, f(H2O), f, the single-pass extraction fraction of [(18)F]fluoride (E) and the volume of distribution (DV) of [(18)F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f(H2O) and K(i) values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [(18)F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [(18)F]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease after gastrectomy is mainly related to an up-regulation of the amount of ionic exchange of [(18)F]fluoride with the bone matrix, while tracer delivery remains unchanged.

Expression of 5-HT3 receptors in the rat gastrointestinal tract.

BACKGROUND & AIMS: Functional effects mediated via the 5-hydroxytryptamine3 receptor (5-HT3R) can be elicited from both extrinsic and intrinsic neurons innervating the gastrointestinal (GI) tract. Clinically, 5-HT3 antagonists are important in the treatment of emesis and have been used for the treatment of symptoms in functional bowel disease. The aim of the present study was to elucidate the cellular sites of 5-HT3R expression in the rat GI tract using immunohistochemistry. METHODS: Immunohistochemistry was performed in fixed cryostat sections and whole mounts of stomach and intestine of fasted rats, using an affinity-purified antibody directed to a 19-amino acid sequence of the cytoplasmic loop of the 5-HT3R. RESULTS: 5-HT3R immunoreactivity was localized to numerous neurons of the myenteric and submucosal plexus, concentrated primarily near the neuronal plasma membrane, and to fibers in the circular and longitudinal muscles, submucosa, and mucosa. 5-HT3R immunoreactivity was also expressed by interstitial cells of Cajal and a few endocrine cells. Numerous 5-HT3R-positive myenteric neurons were cholinergic, and few neurons coexpressed VIP or SP immunoreactivity. Fibers immunoreactive for 5-HT3R in the duodenal but not ileal mucosa were markedly reduced by subdiaphragmatic vagotomy or chemical denervation of vagal afferents. CONCLUSIONS: These findings indicate that 5-HT3Rs are expressed by distinct cells in the GI tract, including functionally distinct classes of neurons, interstitial cells of Cajal, and endocrine cells. The effects of serotonin mediated by 5-HT3Rs involve the activation of neuronal and nonneuronal pathways.

Telemetric small intestinal motility recording in awake rats: a novel approach.

INTRODUCTION: Ideally, gastrointestinal motility recording should be done in freely moving, stress-free animals. However, no such method is currently available for rats. METHODS: Two NiCr electrodes were sutured to the jejunum and connected to an implantable electromyographic (EMG) transmitter in rats. EMG signals were radio-transmitted to a receiver placed at the bottom of the rats' home cages. RESULTS: Fasting and postprandial jejunal EMG signals could be detected by telemetry. Phase III contractions of the MMC were easy to identify visually and occurred at a rate of about 4.8 per hour. Feeding disrupted the phasic contraction pattern 15 min after the start of food intake and lasted for 2 h. The motility index (MI, area under the curve) was calculated and increased postprandially. CONCLUSION: Telemetric transmission of rat gastrointestinal EMG signals is feasible and results are comparable to those given in the literature.

Chylomicron components mediate intestinal lipid-induced inhibition of gastric motor function.

Lipid, particularly long-chain triglyceride, initiates feedback regulation of gastrointestinal function. To determine whether the site of action of lipid is pre- or postabsorptive, we investigated the ability of mesenteric lipid-fed lymph to inhibit gastric motor function. Lymph was collected from awake lymph-fistula rats during intestinal infusion with either a glucose-saline maintenance solution or lipid. Intra-arterial injection of lymph collected during intestinal lipid infusion significantly inhibited gastric motility in anesthetized recipient rats compared with injection of equivalent amounts of triglyceride or lymph collected during intestinal infusion of maintenance solution. Lymph collected from rats during lipid infusion with Pluronic L-81 [an inhibitor of chylomicron formation and apolipoprotein (apo) A-IV secretion] compared with lymph injection from donor animals treated with Pluronic L-63 (a noninhibitory control for Pluronic L-81) was significantly less potent. Injection of purified recombinant apo A-IV significantly inhibited gastric motility. Products of lipid digestion and absorption, other than fatty acids or triglyceride, released by the intestine during lipid digestion likely serve as signals to initiate intestinal feedback regulation of gastrointestinal function. Most likely, apo A-IV is one of the signals involved.