A gamma variate model that includes stretched exponential is a better fit for gastric emptying data from mice

Abstract

Bajzer Ž, Gibbons SJ, Coleman HD, Linden DR, Farrugia G. A gamma variate model that includes stretched exponential is a better fit for gastric emptying data from mice. Am J Physiol Gastrointest Liver Physiol 309: G162-G170, 2015. First published June 4, 2015; doi:10.1152/ajpgi.00280.2014.-Noninvasive breath tests for gastric emptying are important techniques for understanding the changes in gastric motility that occur in disease or in response to drugs. Mice are often used as an animal model; however, the gamma variate model currently used for data analysis does not always fit the data appropriately. The aim of this study was to determine appropriate mathematical models to better fit mouse gastric emptying data including when two peaks are present in the gastric emptying curve. We fitted 175 gastric emptying data sets with two standard models (gamma variate and power exponential), with a gamma variate model that includes stretched exponential and with a proposed two-component model. The appropriateness of the fit was assessed by the Akaike Information Criterion. We found that extension of the gamma variate model to include a stretched exponential improves the fit, which allows for a better estimation of T 1/2 and Tlag. When two distinct peaks in gastric emptying are present, a two-component model is required for the most appropriate fit. We conclude that use of a stretched exponential gamma variate model and when appropriate a two-component model will result in a better estimate of physiologically relevant parameters when analyzing mouse gastric emptying data. motility; smooth muscle; gastrointestinal tract; empirical mathematical models THE MEASUREMENT OF GASTRIC emptying in human subjects and animal models of disease is an important technique for understanding the changes in gastric motility that occur under normal physiological conditions, in disease, or in response to drugs. Acute physiological changes in gastric emptying can be identified in response to the content and nature of a meal including the effects of calories, osmolarity, lipid, protein, and carbohydrate content (9). Determination of gastric emptying has clinical relevance since the delay of gastric emptying of solids is required for positive diagnosis of gastroparesis. Gastroparesis can occur secondary to drugs or systemic disease as a complication of diabetes or remain idiopathic (21). Accelerated gastric emptying is also observed in subsets of patients with symptoms suggestive of functional dyspepsia, or dumping, as well as in a subset of patients with diabetes particularly early after diagnosis (12,25). Accelerated gastric emptying is also observed in animal models of diabetes (7). Prokinetic agents have been identified and studied by using gastric emptying tests in experimental animals and candidate drugs have been tested for unwanted effects on gastric emptying (24).Several noninvasive tests have been developed to follow gastric emptying in humans including scintigraphy and breath tests (5, 29), and some of these tests have been applied for ...

High temporal resolution gastric emptying breath tests in mice

“…The recently developed tool for analysis of gastric emptying data is able to detect two‐peak gastric emptying curves that may be an indication of saltatory rather than steady‐state emptying. We tested the hypothesis that delayed gastric emptying in diabetic mice is associated with an increased occurrence of two peak gastric emptying curves.…”

“…Gastric emptying curves that contain a second peak (ie more than one phase), although rare, has been observed in previous literature in both mice and humans with the solid meal . However, a mathematical expression that was versatile enough to fit these data has only recently been described . Putting to use our increased temporal resolution and analysis tool, the potential physiological bases for the presence of these two‐peak curves were investigated.…”

“…Output tables generated by the CO 2 analyzer containing delta 13 C values, the sampled chamber and time, were analyzed using a custom Linux based system described previously. 20 Only the empirical models GVS and GVS2 were used for this study. The GVS model produced output values of T 1/2 , the time (min) to half emptying, T lag , the time (min) to peak gastric emptying, and Max R, or maximal rate of 13 CO 2 production.…”

“…All data from these studies were stored in our custom Electronic Animal Research Record (EARR) relational database. This affords us to retrospectively analyze these data using our newly developed LINUX‐based software . We randomly retrieved data from two different mouse models of diabetes, NOD/ShiLtJ and B6;C3Fe a/a‐Csf1<+>, from the database using search criteria of diabetic (>250 mg/dL), non‐diabetic (<150 mg/dL), and normal vs delayed gastric emptying using criteria set by the published study .…”

“…Output tables generated by the CO 2 analyzer containing delta 13 C values, the sampled chamber and time, were analyzed using a custom Linux based system described previously . Only the empirical models GVS and GVS2 were used for this study.…”