BACKGROUND: There is no single gold standard for investigation of gastrointestinal motility function. Wireless motility monitoring involves a novel concept which provides a complex information on gastrointestinal function (gastrointestinal transit time, intra-luminal pH, pressure and temperature). Gastrointestinal motility functions of experimental pigs are very similar to those of humans. That is why porcine studies have already provided suitable experimental models for several preclinical projects. AIMS: The aim of our study was to adopt methods of non-invasive wireless monitoring of gastrointestinal functions in experimental pigs. METHODS: Five experimental adult female pigs were enrolled into the study. Wireless motility capsules were delivered into the porcine stomach endoscopically. Gastrointestinal transit and intra-luminal conditions were recorded for five days. RESULTS: Records of animals provided good (3 pigs) or very good quality files (2 pigs). 31150 variables were evaluated. Mean time of the presence of capsules in the stomach was 926 ± 295 min, transfer of a capsule from the stomach into the duodenum lasted 5-34 min. Mean small intestinal transit time was 251 ± 43 min. Food intake was associated with an increase of gastric luminal temperature and a decrease of intra-gastric pressure. The highest intra-luminal pH was present in the ileum. The highest temperature and the lowest intra-luminal pressure were found in the colon. All data displayed a substantial inter-individual variability. CONCLUSIONS: This pilot study has proven that a long-term function monitoring of the gastrointestinal tract by means of wireless motility capsules in experimental pigs is feasible. However, both ketamine-based induction of general anaesthesia as well as long-lasting general anaesthesia (> 6 hours) should be avoided to prevent retention of a capsule in the porcine stomach.
BACKGROUND: Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer's disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. METHODS: Six experimental adult female pigs (Sus scrofa f. domestica, hybrids of Czech White and Landrace breeds; 3-month-old; mean weight 30.7 ± 1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes). RESULTS: In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV2) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p = 0.001) and T10 (992.5; 385-2859; p = 0.032). In group B, the dominant frequency increased significantly from basal values (1.97 ± 1.57 cycles per minute) to intervals T9 (3.26 ± 2.16; p < 0.001) and T10 (2.14 ± 1.16; p = 0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p = 0.002) and T8 (799; 435-1463 μV2; p = 0.004). CONCLUSIONS: Both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings might provide a possible explanation of rivastigmine-associated dyspepsia in humans.
- MeSH
- Alzheimerova nemoc * MeSH
- cholinesterasové inhibitory farmakologie MeSH
- elektromyografie MeSH
- fenylkarbamáty farmakologie MeSH
- gastrointestinální trakt MeSH
- kojenec MeSH
- lidé MeSH
- rivastigmin farmakologie MeSH
- žaludek * MeSH
- zvířata MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod: Téměř všechny preklinické studie u experimentálních prasat je třeba provádět v celkové anestezii. Ketamin je běžně používán jako úvod do anestezie. Avšak dosud nezodpovězenou otázkou je, zda ketamin, antagonista NMDA-receptorů, ovlivňuje motorické funkce žaludku. Cílem této práce bylo vyšetřit žaludeční myoelektrickou aktivitu prasete metodou elektrogastrografie (EGG). Metody: Do studie bylo zařazeno 17 samic Sus scrofa f. domestica (průměrná hmotnost 36,2 ± 3,8 kg). Pro úvod do anestezie byla použita různá léčiva: skupina A (n = 5): medetomidin 0,1 mg/kg i. m.; butorfanol 0,3 mg/kg i. m.; midazolam 0,3 mg/kg i. m.; skupina B (n = 6): azaperon 2,2 mg/kg i. m.; skupina C (n = 6): ketamin 20 mg/kg i. m.; azaperon 2,2 mg/kg i. m. Celková anestezie ve všech skupinách pokračovala podáváním 1% propofolu (opakované 1ml bolusy, celkem 10–12 ml i.v.). Záznam EGG začal za 15 min. po úvodu do anestezie a trval 30 min. Výsledky byly vyhodnoceny jako dominantní frekvence pomalých žaludečních vln (DF) a plochy pod křivkou (EGG power). Výsledky: Celkem bylo vyhodnoceno 510 jednominutových EGG intervalů (každý dvakrát: DF a power). DF byly (průměr ± směrodatná odchylka): 1,4 ± 0,4 (skupina A), 1,3 ± 0,3 (skupina B) a 0,2 ± 0,1 cykly/min. (skupina C). Rozdíly mezi skupinou C a skupinami A a B byly statisticky významné (p < 0,001). Mediány ploch pod křivkou (IQR) byly: 0,13 (0,02–0,44; skupina A); 0,13 (0,03–0,54; skupina B) a 0,30 V2 (0,07–1,44; skupina C). Rozdíl mezi skupinami A a C byl na hranici statistické významnosti (p = 0,066; chyba 2. typu beta 0,295). Závěry: Ketamin, a to i v jedné intramuskulární dávce, ovlivňuje myoelektrické funkce žaludku prasete. Proto by neměl být používán v preklinických studiích gastrointestinální motility experimentálních prasat.
Introduction: Preclinical studies in experimental pigs are carried out mostly under general anaesthesia. Ketamine is commonly used for induction of anaesthesia. However, there are concerns that ketamine, an NMDA-receptor antagonist, may influence gastric motor function. The aim of this study was to investigate porcine gastric myoelectric activity by means of electrogastrography (EGG). Methods: Seventeen female animals (mean weight 36.2±3.8 kg) were enrolled. Drugs used for induction of anaesthesia were: Group A (n=5): medetomidine 0.1 mg/kg i. m.; butorphanol 0.3 mg/kg i. m.; midazolam 0.3 mg/kg i. m.; Group B (n=6): azaperon 2.2 mg/kg i. m.; Group C (n=6): ketamine 20 mg/kg i. m.; azaperon 2.2 mg/kg i. m., followed in all groups by i.v. 1% propofol (repeated one-mL boluses, 10–12 mL in total). EGG recording started 15 min. after the induction administration and lasted 30 min. Results were evaluated as the dominant frequency of gastric slow waves (DF) and EGG power (areas of amplitudes). Results: In total, 510 one-minute EGG intervals were assessed. DFs were (mean ± standard deviation): 1.4±0.4 (Group A), 1.3±0.3 (Group B) and 0.2±0.1 cycles per min. (Group C). The differences between group C and groups A and B were statistically significant (p<0.001). Median power (IQR) was 0.13 (0.02–0.44; Group A), 0.13 (0.03–0.54; Group B) and 0.30 V2 (0.07–1.44; Group C). The difference between groups A and C was of borderline significance (p=0.066; type 2 error beta 0.295). Conclusions: Ketamine, administered even in a single intramuscular dose, affected myoelectric function of the porcine stomach. Therefore, it should be avoided in gastrointestinal motility studies in experimental pigs.
BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.
Galantamine has been used as a treatment for Alzheimer disease. It has a unique, dual mode of action (inhibitor of acetylcholinesterase and allosteric modulator of nicotinic acetylcholine receptors). Nausea (in about 20%), vomiting (10%) and diarrhoea (5-7%) are the most common side effects. The aim of this study was to assess the effect of galantamine on porcine gastric myoelectric activity without (Group A) and with (Group B) dextran sodium sulphate (DSS)-induced gastrointestinal injury. Galantamine hydrobromide was administrated to twelve pigs as a single intragastric dose (24 mg). Gastric myoelectric activity was investigated by electrogastrography (EGG). Basal (15 min before galantamine administration) and study recordings after galantamine administration (300 min) were evaluated using a running spectral analysis. Results were expressed as dominant frequency of gastric slow waves and power analysis (areas of amplitudes). Altogether, 3780 one-minute EGG recordings were evaluated. In Group A, power was steady from basal values for 180 min, then gradually decreased till 270 min (p = 0.007). In Group B, there was a rapid gradual fall from basal values to those after 120 min (p = 0.007) till 300 min (p ˂ 0.001). In conclusion, galantamine alone revealed an unfavourable effect on porcine myoelectric activity assessed by gastric power. It can be a plausible explanation of galantamine-associated dyspepsia in humans. DSS caused further profound decrease of EGG power. That may indicate that underlying inflammatory, ischaemic or NSAIDs-induced condition of the intestine in humans can have aggravated the effect of galantamine on gastric myoelectric activity.
- Publikační typ
- časopisecké články MeSH
Gastrointestinal side effects of donepezil, including dyspepsia, nausea, vomiting or diarrhea, occur in 20-30% of patients. The pathogenesis of these dysmotility associated disorders has not been fully clarified yet. Pharmacokinetic parameters of donepezil and its active metabolite 6-O-desmethyldonepezil were investigated in experimental pigs with and without small intestinal injury induced by dextran sodium sulfate (DSS). Morphological features of this injury were evaluated by a video capsule endoscopy. The effect of a single and repeated doses of donepezil on gastric myoelectric activity was assessed. Both DSS-induced small intestinal injury and prolonged small intestinal transit time caused higher plasma concentrations of donepezil in experimental pigs. This has an important implication for clinical practice in humans, with a need to reduce doses of the drug if an underlying gastrointestinal disease is present. Donepezil had an undesirable impact on porcine myoelectric activity. This effect was further aggravated by DSS-induced small intestinal injury. These findings can explain donepezil-associated dyspepsia in humans.
- MeSH
- donepezil chemie farmakokinetika farmakologie MeSH
- gastrointestinální trakt účinky léků patologie patofyziologie MeSH
- indany metabolismus MeSH
- kapslová endoskopie MeSH
- metabolom * účinky léků MeSH
- migrující myoelektrický komplex * účinky léků MeSH
- piperidiny metabolismus MeSH
- prasata MeSH
- síran dextranu MeSH
- žaludek účinky léků patofyziologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). METHODS: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). RESULTS: Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 μV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 μV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 μV^2; p<0.001), lasting till 120 min. (p<0.001). CONCLUSIONS: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.
- MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- antagonisté excitačních aminokyselin aplikace a dávkování škodlivé účinky MeSH
- aplikace orální MeSH
- elektromyografie MeSH
- gastrointestinální motilita účinky léků fyziologie MeSH
- gastrointestinální nemoci chemicky indukované diagnóza patofyziologie MeSH
- lidé MeSH
- memantin aplikace a dávkování škodlivé účinky MeSH
- modely nemocí na zvířatech MeSH
- Sus scrofa MeSH
- žaludek účinky léků patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
