小动物胃肠蠕动的评价方法

GASTROINTESTINAL MOTILITY – CLINICAL ASSESSMENT IN SMALL ANIMALS Frédéric P. Gaschen, Dr.med.vet., Dr.habil., DACVIM, DECVIM-CA Baton Rouge, Louisiana, USA INTRODUCTION In people, disorders of gastrointestinal (GI) motility are common reasons for patients to visit their physician 1 . They include a variety of problems such as heartburn, regurgitation, dysphagia, bloating, postprandial fullness, early satiety, and constipation. In dogs, the prevalence of GI motility disorders cannot be documented precisely due to difficulty in obtaining a definitive diagnosis 2,3 . Examples of such diseases include megaesophagus, disorders of gastric emptying, functional intestinal obstruction (ileus), megacolon and constipation. 3,4 In dogs, abnormal gastric motility can lead to the feared and potentially fatal gastric dilation-volvulus (GDV) syndrome. More generally, disorders of GI motility can cause discomfort in small animals and their diagnosis and treatment is often challenging to general practitioners and specialists alike. A variety of primary and secondary gastric defects have been identified as potential causes gastric atony. 5 To this day, the timely recognition and proper diagnosis of GI motility disorders in small animals has been hampered by the lack of a practical, non-invasive ways to evaluate GI motility. PHYSIOLOGY OF GI MOTILITY - A BRIEF REFRESHER 6,7,8 GI motility is obviously a very complex series of events that aims at (1) storing and (2) grinding the ingested food into particles of a determined size before they are ejected out of the stomach and (3) propel the ingesta through the small intestine while allowing the digestive and absorptive processes to take place harmoniously and (4) optimize conditions for fermentation and water reabsorption processes in the proximal colon and (5) store and coordinate evacuation of fecal material from the distal colon and rectum. While GI motility is a function of smooth muscle contraction, a combination of myogenic, neural, and hormonal factors regulate smooth muscle activity 6 . The gastric antrum acts as a pump from which peristaltic waves originate while the gastric body acts as a high compliance reservoir. Contractions only occur when excitatory neurotransmitters such as acetylcholine are released in response to mechano- and chemoreceptors. The mechanical action of the antral pump is divided 3 phases: (1) propulsion, (2) emptying of fine particles and mixing, and (3) retroplusion of particles > 2 mm and grinding. Gastric motility and emptying are modulated by gastro-gastric reflexes: for instance filling and distention of the gastric reservoir elicits excitatory reflexes stimulating antral contractions. Nitric oxide (NO) and vasoactive intestinal peptide (VIP) contribute to the regulation of gastric motility. Gastric emptying is inhibited by nutrients entering the small intestine (feedback control) through entero-gastric reflexes and release of intestinal hormones. Cholecystokinin (CCK) is released from I cells in the intestinal epithelium upon presence of luminal HCl, amino acids and long-chain fatty acids. CCK reaches the stomach via bloodstream, causes relaxation of the gastric reservoir and reinforces enterogastric neural feedback. Other hormones such as glucagon-like peptide 1 (GLP-1) and peptide YY produced in the distal small intestine also exert a negative feedback on gastric emptying. Additionally, the rate of gastric emptying in dogs is modulated by the composition of the diet (e.g. moisture and fat, protein and carbohydrate content) 9 and other factors such as stress and body size. A network of interstitial cells (interstitial cells of Cajal or ICC) exists the gastric and intestinal wall between the internal circular and external longitudinal muscle layers. ICC produce pacesetter potentials and drive the electrical events in the smooth muscle cells (slow waves). Pacesetter potentials determine the maximal frequency and propagation velocity of the peristaltic waves. Different contractile patterns occur in the small intestine and include peristaltic waves, stationary segmenting contractions, aboral giant contractions and stationary/migrating clusters of contractions. Phase III contractions also called migrating motor complexes (MMC) occur in the interdigestive state and originate simultaneously in the stomach and in the duodenum. They clean the corresponding gastrointestinal segments of residues and chime. Finally, canine colonic motility consists of organized groups of contractions called colonic motor complexes (CMC) and giant contractions which are usually associated with defecation. MEASUREMENT OF GI MOTILITY IN DOGS AND CATS The various methods available to investigate gastric emptying have been recently reviewed 8 . They aim at evaluating the gastric emptying and/or intestinal transit time of solid food, and include scintigraphy, radiographic contrast studies, abdominal ultrasound, gastric emptying breath test, and passive telemetry 14 . While the latter method is invasive and impractical for use in privately owned pet dogs, the other methods are non-invasive, but all have potential pitfalls 8 . Additionally, some of them require manual or chemical restraint of the animals, a potential source of stress. Radioscintigraphy remains the gold standard In human medicine, radioscintigraphic evaluation of gastric emptying is a standardized method and reference ranges based on large study populations are available. The technique involves the use of 99m Technetium-associated compounds in most instances. It has also been used widely in small animals. Dispersion of radiolabeled food among the ingested test meal may vary and influence the results. Although scintigraphy is a useful standard against which to compare newer methods, it is not a widely used method to assess disorders of gastric emptying in dogs and cats. The availability of the equipment and the special safety requirements for use of radionuclides are the most important limiting factors. Radiographic contrast studies Liquid barium has been widely used to assess GI transit times and is adequate to evaluate liquid phase gastric emptying. The dose of barium suspensions is 6 ml/kg in dogs and 10 ml/kg in cats and should be administered when the stomach is empty. Barium sulfate should be present in the duodenum by 15 minutes in the dog and by 5 minutes in the cat. The stomach should be free of barium after 1 to 4 hours in the dog and after 20 minutes in the cat. However, assessment of gastric emptying of liquid is an insensitive method for the detection of abnormalities in gastric emptying, with the exception of mechanical obstructions due to foreign bodies or other space-occupying lesions obstructing the gastric or intestinal lumen. Mixing barium with food may better evaluate the solid phase of gastric emptying, however barium can easily separate from the test meal and cause the study to be unreliable. Barium-impregnated polyethylene spheres (BIPS TM ) have been used for evaluation of GI transit times in dogs and cats. They come in various sizes (from 1.5 to 5 mm diameter) and can easily be used in practice. However, correlation between gastric emptying of BIPS and radioscintigraphy has been disappointing in dogs and in cats. 15,16 This probably reflects the facts that BIPS > 2 mm are only emptied after all solid food has left the stomach during the interdigestive MMC. At this time, it is not clear if evaluation of the time between ingestion of indigestible markers and onset of gastric MMC is useful in the evaluation of gastric motility disorders of small animals or humans. Ultrasound evaluation of gastric emptying time Qualitative evaluation of GI motility using ultrasonography is regularly performed during abdominal scans. Recently, ultrasound was shown to be a reliable and accurate quantitative method to measure emptying of liquids and solids from the stomach when compared to standard methods. 10-12 Dogs are gently restrained while standing and the ultrasound transducer is placed in a longitudinal orientation on to the ventral midline, caudal to the xyphoid. Electronic calipers are used to measure the cranio-caudal and ventro-dorsal diameters of the gastric antrum. The antral area is calculated using the software incorporated in the ultrasound machine. Measurements are made at each of the following each time points: 30 min. prior to feeding, then every 20 min. post-prandially for 6 hours. Gastric half-emptying time (50% of AUC), time of maximal antral area, and time at which antral area was reduced by 50% can be calculated. 11 This method is easily applicable to clinical patients but requires the availability of an experienced ultrasonographer. Tracer studies The assessment of gastric emptying by stable isotope breath tests relies on the ingestion of a 13 C-labeled substrate that is rapidly absorbed and metabolized to 13 CO2 after gastric emptying. This produces an increase in 13 CO2 in the exhaled air that can be relatively easily measured. 8 Recently, the 13 C-octanoic breath test has been validated for use in both dogs and cats. 13,17 Octanoic acid is a medium chain fatty acid that is rapidly absorbed in the duodenum, oxidized in the liver where it produces CO2 which is exhaled in the breath. 13 Exhaled air is collected at several time points after the test meal added with 13 C octanoic acid has been ingested. The method is non-invasive and the whole procedure can be done outside the veterinary hospital. Analysis of exhaled air for 13 C is automated and provides useful data about the dynamics of gastric emptying. Non-invasive monitoring pH, pressure and temperature during GI transit A new method for non-invasive evaluation of GI motility has been recently approved for use in human patients. Patients ingest a large 13x26 mm non-digestible capsule with pH, pressure, and temperature sensors (SmartPill pHp TM ). It immediately transmits measurements to a receiver/recorder located on the dogs back. The information can then be uploaded in a dedicated computer and be processed in detail. Typically, gastric emptying time, small intestinal/colonic transit time, and total GI transit times are calculated. However, detailed data about pH, pressure and temperature can be collected for specific time points using proprietary software for data interpretation. Studies from Lousiana State University and from another institution validating the use of this capsule in the dog and evaluating its sensitivity in reporting changes due to dietary modifications and various drugs influencing GI motility yielded promising results. They will be reported in the scientific abstract session of this meeting. Due to its size, the SmartPill capsule only leaves the stomach at the onset of the interdigestive MMC when all liquids and solids have already been propelled into the small intestine. Additionally, the pill size also limits its use exclusively to dogs larger than approximately 15 kg body weight. REFERENCES 1. Parkman and Doma. Practical Gastroenterology 2006; 30: 23. 2. Hall and Washabau. Veterinary Clinics of North America - Small Animal Practice 1999; 29: 377. 3. Washabau. Veterinary Clinics of North America - Small Animal Practice 2003; 33: 1007. 4. Guilford 1996; Strombeck's Small Animal Gastroenterology, 3rd ed: 532. 5. Woosley. Clinical Techniques in Small Animal Practice 2004; 19: 43. 6. Strombeck 1996; Strombeck's Small Animal Gastroenterology, 3rd ed: 1. 7. Ehrlein and Schemann, 2007, Technical University Munich: http://www.wzw.tum.de/humanbiology/data/motility?alt=english; 8. Wyse et al. J.Vet.Int.Med. 2003; 17: 609. 9. Davenport et al. 2000 Small Animal Clinical Nutrition, Mark Morris Associates; 725. 10. Choi et al. J.Vet Med.Sci. 2002; 64: 17. 11. McLellan et al. AJVR 2004; 65: 1557. 12. Chalmers et al. Veterinary Record 2005; 157: 649. 13. Wyse et al. AJVR 2001; 62: 1939. 14. Burger et al. Journal of Veterinary Medicine Series A: Physiology Pathology Clinical Medicine 2006; 53: 85. 15. Goggin et al. Vet Radiol Ultrasound 1999; 40: 89. 16. Lester et al. Veterinary Radiology and Ultrasound 1999; 40: 465. 17. Peachey, Dawson, and Harper. Comp Biochem.Physiol A Mol.Integr.Physiol 2000; 126: 85.