Stable isotope tracer studies for the measurement of equine gastrointestinal motility

Abdominal disorders are a major cause of morbidity and mortality in horses, and abnormal gastrointestinal motility may be a significant factor in the aetiopathogenesis of many equine colic syndromes. The understanding of such conditions is hampered by the lack of suitable noninvasive tests for the quantitative measurement of intestinal transit. The overall objective of this work was to investigate the potential value of stable 13C-isotope breath tests for the assessment of specific parameters of equine gastrointestinal motility. A new method developed for the collection of equine expiratory breath and measurement of its ratio was shown to have excellent repeatability. Assessment of peripheral blood tracer content was also performed and correlated significantly to that of concurrent breath samples. In the first study, the 13C-octanoic acid breath test (13C-OABT) was evaluated for the measurement of solid phase gastric emptying rate in 12 healthy horses by direct comparison with the predicate method of gastric scintigraphy. Having shown that the 13C-OABT was a reliable diagnostic procedure for use in healthy horses, a further study was performed against scintigraphy in subjects with atropine-induced gastroparesis (n = 8) to determine whether the test remained accurate when emptying rate was markedly prolonged. In study 3, the 13C-OABT was applied to measure the relative and dose-related effects of common sedative agents on solid phase gastric emptying in 8 horses. The study results may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia. The 13C-bicarbonate and sodium 13C-acetate breath tests were investigated in study 4 for the assessment of equine liquid phase gastric emptying, and elucidation of the pattern of 13CO2 recovery from the body bicarbonate pool. The lactose 13C-ureide breath test (13C-LUBT) was investigated in study 5 for estimation of orocaecal transit time (OCTT), and concurrent comparison made to the hydrogen breath test (H2BT). In study 6 the induced 13C-LUBT was evaluated in vivo for the measurement of OCTT and a mean (+/- s.d.) time of 3.24 (+/- 0.65) h was gained. In order to examine the relationship between gastric emptying of solid ingesta, small bowel transit and its arrival in the caecum, a combined test was developed and applied in study 7, incorporating both 13C-OA and 13C-LU. Mathematical modelling of 13C recovery after ingestion of the dual test meal allowed calculation of small bowel half transit time, in addition to gastric and caecal parameters. Finally, minimised test protocols were developed for the 13C-OABT and 13C-LUBT in order to increase their clinical utility. The effects of decreasing the duration or frequency of breath collection on generation of intestinal transit parameters were assessed and linear regression models produced for each test based on the collection of 5 breath samples. Gastric t1/2, tlag and OCTT estimates from the reduced model and the full sampling protocols were highly correlated. However, in each case the reduced models were likely to underestimate these parameters when significantly prolonged, decreasing their sensitivity for the detection of delayed intestinal transit. The stable isotope breath tests offer a novel means of investigating features of intestinal motility and physiology in the horse and have potential value as both diagnostic modalities and humane research tools in this species. As the tests are non-invasive, simple to perform and do not require extensive equipment, they may be performed on site and the samples then submitted for isotopic analysis. Unlike other techniques for assessment of equine gastrointestinal motility, the stable isotope breath tests also provide an indirect measure of the transit rate of ingesta itself, which is directly relevant to the clinical situation. (Abstract shortened by ProQuest.)