Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses

OBJECTIVE: To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. ANIMALS: 6 mature horses. PROCEDURE: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness of fit of the data. Serial serum samples were taken, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 240 minutes and the absorption constant (Ka) were determined, using a parameter estimation program. Correlations were calculated, using the Spearman rank correlation coefficient. RESULTS: Correlations between T50 and Tmax and between T50 and Ka were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tmax and Ka are valuable variables in the assessment of liquid-phase gastric emptying using acetaminophen absorption. Acetaminophen absorption may be a valuable alternative to nuclear scintigraphy in the determination of gastric emptying rates in equine patients with normally functioning small intestine.     

Evaluation of acetaminophen absorption in horses with experimentally induced delayed gastric emptying

OBJECTIVE: To evaluate the correlation between the half-time of liquid-phase gastric emptying (T50) determined by use of nuclear scintigraphy, using technetiumTc 99m pentetate, and absorption variables of orally administered acetaminophen in horses with experimentally delayed gastric emptying. ANIMALS: 6 mature horses. PROCEDURE: Delayed gastric emptying was induced by IV injection of atropine sulfate. Twenty minutes later, acetaminophen and technetium Tc 99m pentetate were administered simultaneously via nasogastric tube. Serial lateral images of the stomach region were obtained, using a gamma camera. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness-of-fit of the data. Serial serum samples were obtained, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 480 minutes, and the appearance rate constant were determined, using a parameter estimation program. Correlations were calculated, using a Spearman rank correlation coefficient. RESULTS: A significant correlation was detected between T50 determined by use of scintigraphy and Tmax determined by use of acetaminophen absorption. Correlation between T50 and other absorption variables of acetaminophen was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The acetaminophen absorption method was a valid technique in this model of delayed gastric emptying in horses. The method may be a valuable tool for use in research as well as in clinical evaluation of gastric emptying in horses.     

Retention of acetaminophen in an in vitro model of solid-phase gastric emptying of animals

OBJECTIVE: To apply an in vitro model for assessment of the solid-phase binding capacity of acetaminophen and thus assess the reliability of this marker for evaluation of solid-phase gastric emptying in vivo in animals. SAMPLE POPULATION: 4 test meals. PROCEDURES: A spectrophotometric method for detection of acetaminophen was validated and applied for assessment of the percentage retention of acetaminophen in the solid phase of 4 test meals. The gastric milieu was simulated by incubating each meal in artificial gastric juice for 2 hours in a shaking water bath maintained at 37 degrees C. Solid-phase retention was then assessed 3 times by measuring the amount of acetaminophen that had leached into the liquid phase. RESULTS: Acetaminophen was poorly retained in the solid phase of all the test meals examined in the study. There was also a large degree of variability in the percentage retention for each meal when the experiment was repeated 3 times. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results of this in vitro study confirmed that acetaminophen may not be an appropriate marker of solid-phase gastric emptying. The acetaminophen gastric emptying test should be applied only for the assessment of liquid-phase emptying in animals.     

Validation of the 13C-octanoic acid breath test for measurement of equine gastric emptying rate of solids using radioscintigraphy

REASONS FOR PERFORMING STUDY: Disordered gastric motility may be a significant factor in the pathogenesis of many equine conditions. Although tests for liquid phase emptying rate have been validated in the horse, there are no effective tests for solid phase emptying measurement that can be performed routinely in the field. OBJECTIVES: The objective of this study was the assessment of a novel stable isotope technique, the 13C-octane acid breath test (13C-OABT), for the measurement of gastric emptying of solid ingesta, by direct comparison with the optimum method of gastric scintigraphy. METHODS: To facilitate dual measurement of gastric emptying, a test meal was used containing baked egg yolk labelled with both 13C-octanoic acid and 99mtechnetium sulphur colloid. Simultaneous, serial lateral gastric scintigraphs and expiratory breath samples were obtained in 12 healthy horses after voluntary ingestion of the test meal. Analysis of breath 13CO2:12CO2 ratio was performed by continuous flow isotope ratio mass spectrometry. Power regression was used to determine the gastric emptying coefficient, the gastric half-emptying time (t 1/2) and duration of the lag phase (tlag). RESULTS: Significant correlations (P < 0.001) were found between the 2 techniques for measurement of both t 1/2 and tlag. In addition, scintigraphic left t 1/2 was correlated significantly to breath test gastric emptying coefficient (P < 0.001). CONCLUSIONS: It was concluded that the 13C-octanoic acid breath test is a reliable diagnostic procedure to measure gastric emptying rate of solids in the horse. POTENTIAL RELEVANCE: Being safe, noninvasive and easy to perform, this test has potential value as both sensitive diagnostic modality and humane research tool for motility studies.     

Comparison of the carbon 13-labeled octanoic acid breath test and ultrasonography for assessment of gastric emptying of a semisolid meal in dogs

OBJECTIVE: To compare the rate of gastric emptying of a semisolid meal by use of the carbon 13-labeled octanoic acid breath test (13C-OBT) and gastric emptying ultrasonography (GEU) in dogs. ANIMALS: 10 healthy dogs. PROCEDURE: Food was withheld from dogs for 12 hours before ingestion of a test meal (bread, egg, and skimmed milk) containing 13C-octanoic acid. The gastric antrum was visualized by use of a 6.5-MHz microconvex transducer, and the area of the ellipse defined by the craniocaudal and ventrodorsal diameters of the stomach was measured. Samples of expired air and antral images were obtained 30 minutes before ingestion of the test meal and then every 15 minutes for 4 hours and every 30 minutes for a further 2 hours. The half-dose recovery time with the 13C-OBT (t1/2[BT]) and the gastric half emtying time with GEU (t50%[GEU]) was calculated. RESULTS: Mean +/- SD values for the t1/2(BT) and t50%(GEU) were 3.44 +/- 0.48 hours and 1.89 +/- 0.78 hours, respectively. A significant correlation was detected between the t1/2(BT) and t50%(GEU), although there was a large (1.55 hours) mean difference between these indices. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that there was a correlation between the rate of solid-phase gastric emptying assessed by use of GEU and the 13C-OBT in dogs. Gastric emptying ultrasonography may be a useful, noninvasive method for assessment of the rate of solid-phase gastric emptying in dogs.     

Use of the 13C-octanoic acid breath test for assessment of solid-phase gastric emptying in dogs.

OBJECTIVE: To assess the 13C-octanoic acid breath test for determining gastric emptying in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURE: Food was withheld for 12 hours before each test. Expired air was collected 30 minutes and immediately before each test and at frequent intervals thereafter for 6 hours. Concentration of 13CO2 in expired air was determined by use of continuous-flow isotope-ratio mass spectrometry. Basal concentration of 13CO2 was measured in dogs that were not fed a test meal. Effects of the standard unlabeled test meal on basal concentration of 13CO2 were then assessed. The optimum dose of substrate was determined by measuring 13CO2 concentration after ingestion of the standard test meal containing 50 or 100 mg of 13C-octanoic acid, whereas effect of energy density of the test meal on gastric emptying was determined after ingestion of the standard or high-energy labeled test meal. Gastric emptying coefficient (GEC), time to peak 13CO2 concentration (tmax), and half-dose recovery time (t(1/2)) were calculated. RESULTS: Basal concentration of 13CO2 in expired air was not significantly affected by ingestion of the unlabeled test meal. However, 13CO2 concentration significantly increased in a dose-dependent manner after ingestion of the labeled meal. Gastric emptying coefficient, and were significantly different between dogs fed the standard and high-energy test meals, indicating that ingestion of a high-energy meal delays gastric emptying. CONCLUSIONS AND CLINICAL RELEVANCE: The 13C-octanoic acid breath test may be a useful noninvasive and nonradioactive method for assessment of gastric emptying in dogs.     

Gastric emptying of liquids in the dog: effect of volume

Effect of liquid test meal volume on gastric emptying was investigated in healthy nonoperated dogs fed meal sizes of 6.6 to 110 ml/kg of body weight. For meals less than or equal to 66 ml/kg, the amount of test meal emptied from the stomach in 30 minutes vs meal size could be described as following a linear, exponential, or square root pattern. Deviation from these patterns was seen with test meals of 77, 88, and 110 ml/kg. A mean +/- SEM maximum of 0.99 +/- 0.06 ml/kg/min of liquid test meal was emptied from the stomach of dogs fed test meals of 77, 88, and 110 ml/kg. Massive gastric distension induced in dogs during this study did not alter gastric emptying of the liquid test meal.     

THE EFFECT OF INTRAVENOUS DIAZEPAM ON SOLID PHASE GASTRIC EMPTYING IN NORMAL CATS

Intravenous diazepam has been advocated as an appetite stimulant in anorexic cats. Diazepam has also been used to stimulate the intake of radiographic contrast medium-food mixture to determine the gastric emptying time of a solid meal. Diazepam has been suspected to delay gastric emptying in cats. One study found diazepam combined with Valium to have little effect on gastric transit times in cats while diazepam alone accelerates gastric emptying in humans. The purpose of this study was to determine if diazepam influences gastric emptying times in normal cats. The gastric emptying half-time of solid food in normal, non-diazepam treated cats has been previously determined using a scintigraphic technique using ^99mTc-sulfur colloid to radiolabel solid dry food. The median gastric emptying half-time was 2.3 hours and the mean meal size was 16.1 grams. Gastric emptying half-times were determined in this study using diazepam as an appetite stimulant. The median gastric emptying half-times of diazepam tratment groups given both a 16.1 gram meal and a large meal were both significantly longer than the normal non-treated group (P c 0.05). Solid phase gastric emptying is therefore significantly delayed when diazepam is used as an appetite stimulant, irrespective of the volume of the meal.     

Gastric emptying of liquids in the dog: serial test meal and modified emptying-time techniques

A serial test meal technique was used in the dog to evaluate the gastric emptying of a liquid test meal. On separate days, a phenol red test meal was placed in the stomach and completely aspirated at different times. A composite representation of the gastric emptying pattern was obtained for each dog, and a set of normative data was generated. Three emptying determinants (emptying time, half-life, and starting index) were calculated. The basic pattern of canine gastric emptying was linear and declined exponentially or as a function of the square root of the gastric volume. A modified emptying-time technique (METT) correlated well with the serial test meal and a set of normative values was determined. The METT was performed by aspirating test meal from the stomach 30 minutes after instillation. The METT was a simple and inexpensive technique that could be performed in 1 short testing period. With the METT, the half-life of gastric emptying was calculated, using the log of the percentage of retention of test meal; gastric emptying time was calculated, using the square root of the percentage of retention of test meal. Acetylpromazine was shown not to alter gastric emptying of a liquid test meal.     

Effect of sample number and time on determination of plasma clearance of technetium Tc 99m pentetate and orthoiodohippurate sodium I 131 in dogs and cats

OBJECTIVE: To determine the effect of number of blood samples and sampling times on plasma clearance of technetium Tc 99m pentetate (Tc99mP) and orthoiodohippurate sodium I 131(OIH). ANIMALS: 20 dogs and 14 cats. PROCEDURE: Plasma clearances of OIH and Tc99mP were calculated by use of a 2-compartment model, on the basis of a 12-point curve as a reference method. Plasma clearance was calculated by use of all possible combinations of 4 to 11 samples. Time schedule yielding the smallest difference from the reference method was considered to be optimal. Regression analysis was performed between the 12-point model and models using a reduced number of samples. RESULTS: SD of the difference between the 12-point clearance and the models with reduced numbers of samples increased when the number of samples decreased. The SD of the difference between 12-point clearance and 4-point clearance was 4.17 ml/min for OIH and 0.94 ml/min for Tc99mP in dogs and 0.45 ml/min for OIH and 0.11 ml/min for Tc99mP in cats. Optimal schedules were distributed logarithmically and included an early sample at 5 or 10 minutes, a late sample at 2.5, 3, 4, or 5 hours for OIH, and a late sample at 4 or 5 hours for Tc99mP. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearances of OIH and Tc99mP can be accurately calculated in dogs and cats by use of a single-injection 2-compartment pharmacologic model with a reduced number of blood samples, resulting in an acceptable margin of error.     

Use of 13C-acetate breath test for assessment of gastric emptying in horses

This study aimed to establish and standardize a breath test that uses 13C-acetate in a liquid diet for evaluation of gastric emptying in horses. Seven adult healthy thoroughbreds were used in this study. They were given 13C-acetate (125 mg, 250 mg, or 500 mg) in a test meal (2000 ml liquid diet) via an intranasal catheter. 13C concentrations in the exhaled CO2 were measured in samples taken before and after test meal administration using an infrared absorption spectroscope. In the 500 mg 13C-acetate group, Delta13CO2 showed a steep gradient immediately after meal administration compared to the 125 mg and 250 mg groups. Therefore, t(max) in the 500 mg group was easier to determine than in the 125 mg and 250 mg groups. In the 500 mg group, GEC, half-empty time (t1/2), calculated t(max) (t(lag)), and t(max) were 1.95 +/- 0.28 (mean +/- SD), 229.2 +/- 57.0 (min), 139.2 +/- 22.2 (min), and 124.0 +/- 28.4, respectively. Differences in CV observed in the 500 mg group were lower than those in the 125 mg and 250 mg groups. This study demonstrates that the 13C-acetate breath test is useful for evaluating gastric emptying in horses since it is non-invasive and does not require set up of special facilities or equipment. Optimum evaluation of gastric emptying in horses can be achieved with 500 mg of 13C-acetate given in a liquid diet.     

Meal size and starch content affect gastric emptying in horses

REASONS FOR PERFORMING STUDY: Feeding practices have been associated with colic in horses. If meal size and composition have an effect on gastric emptying, this could be one of the mechanisms by which feeding practices are related to the occurrence of colic. OBJECTIVES: To evaluate the effect of meal size and starch content on solid phase gastric emptying. METHODS: Solid phase gastric emptying of 3 different radiolabelled meals, small low-starch (SmLS), small high-starch (SmHS) and large high-starch (LgHS) meals, was measured in 5 horses by scintigraphy using 99mTc-disofenin. Data were compared among meals using nonlinear mixed-effects models and paired t tests. RESULTS: On a percentage basis, SmHS emptied significantly faster than LgHS and SmLS emptied significantly faster than SmHS meals. However, when meals of unequal size were compared by emptying rate in g/min and Kcal/min, LgHS emptied significantly faster than SmHS. CONCLUSIONS: Meal size and composition affect gastric emptying. POTENTIAL RELEVANCE: Further work needs to be performed in order to substantiate the possibility of a relationship between digestive functions and occurrence of colic and gastric ulcers.     

The(13)C-octanoic acid breath test for detection of effects of meal composition on the rate of solid-phase gastric emptying in ponies

The aim of this study was to apply the(13)C-octanoic acid breath test for detection of alterations in the rate of solid-phase gastric emptying, induced by changes in test meal composition, in ponies. After a 14 hour fast the ponies (n = 4) ingested a test meal with 0, 35 or 70 ml soya oil, and labelled with 250 mg(13)C-octanoic acid. Each pony was given each of the three test meals on three separate occasions, in a randomised order. Exhaled breath samples were collected for 12 hours after ingestion of the test meal. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath(13)C-enrichment were computed, half-dose recovery time (t 1/2), gastric emptying coefficient (GEC) and time to peak breath(13)C-excretion t(max). The(13)C-octanoic acid breath test was a reliable means of assessing the significantly decreased rate of gastric emptying in the pony, associated with addition of soya oil to the test meal.     

Effects of indwelling nasogastric intubation on gastric emptying of a liquid marker in horses

OBJECTIVE: To determine the effects of indwelling nasogastric intubation on the gastric emptying rate of liquid in horses. ANIMALS: 6 healthy horses. PROCEDURES: Horses were assigned to treatment and control groups in a prospective randomized crossover study with a washout period of at least 4 weeks between trials. Acetaminophen (20 mg/kg) diluted in 1 L of distilled water was administered via nasogastric tube at time points of 0, 12, 30, 48, and 72 hours to evaluate the liquid-phase gastric emptying rate. In control horses, nasogastric tubes were removed after administration of acetaminophen. In horses receiving treatment, the tube was left indwelling and maintained for 72 hours. A 10-mL sample of blood was collected from a jugular vein immediately before and 20, 40, 60, 80, 100, 120, and 180 minutes after acetaminophen administration. Serum acetaminophen concentrations were measured by use of a colorimetric method. RESULTS: Peak serum acetaminophen concentration was significantly higher in the control group (38.11 microg/mL) than in the treatment group (29.09 microg/mL), and the time required to reach peak serum acetaminophen concentration was significantly shorter in the control group (22.79 minutes) than in the treatment group (35.95 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that indwelling nasogastric intubation has a delaying effect on the gastric emptying rate of liquids. Veterinarians should consider the potential for delayed gastric emptying when placing and maintaining an indwelling nasogastric tube for an extended period of time after surgery. Repeated nasogastric intubation may be better than maintenance of an indwelling tube in horses with ileus.     

The effects of xylazine,detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate

The aim of this study was to measure the effects of specific commonly used sedative protocols on equine solid phase gastric emptying rate, using the 13C-octanoic acid breath test (13C-OABT). The gastric emptying of a standard 13C-labelled test meal was measured once weekly in 8 mature horses over two 4 week treatment periods. Each horse acted as its own control. In treatment Period 1, saline (2 ml i.v.), xylazine (0.5 mg/kg i.v.), detomidine (0.01 mg/kg i.v.) or detomidine/butorphanol combination (0.01/0.02 mg/kg i.v.) was administered in randomised order after ingestion of the test meal. During treatment Period 2, test meal consumption was followed by saline, xylazine (1.0 mg/kg i.v.), or detomidine (0.03 mg/kg i.v.) administration, or preceded by acepromazine (0.05 mg/kg i.m.) in randomised order. The 13C:12C ratio of sequential expiratory breath samples was determined by isotope ratio mass spectrometry, and used to measure the gastric half-emptying time, t 1/2, and duration of the lag phase, t lag, for each of the 64 tests. In treatment Period 1, detomidine/butorphanol prolonged both t 1/2 and t lag with respect to xylazine 0.5 mg/kg and the saline control (P < 0.05). In Period 2, detomidine 0.03 mg/kg delayed each parameter with respect to saline, acepromazine and xylazine 1.0 mg/kg (P < 0.001). Xylazine 1.0 mg/kg also lengthened t lag relative to the saline control (P = 0.0004), but did not cause a significant change in t 1/2. Comparison of treatment periods showed that the inhibitory effect of detomidine on gastric emptying rate was dose related (P<0.05). These findings may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia.     

Ultrasonographic assessment of the rate of solid-phase gastric emptying in dogs

Twelve healthy dogs were used in an ultrasonographic assessment of the effect of the composition of a solid meal on the rate of gastric emptying. The dogs were fasted for nine hours before they were fed either a standard or a high energy density test meal, in a cross-over study design. The gastric antrum was visualised with a 6.5 MHz microconvex transducer, and the area inside the elliptical shape defined by the craniocaudal and ventrodorsal diameters of the stomach was measured. Antral images were acquired at regular intervals for six hours after the ingestion of the test meal. Three indices to describe the rate of gastric emptying were computed: the gastric half-emptying time (t1/2), the time to 50 per cent maximal antral area (t50%), and the time of maximal antral area (tmax). The values of t50% and t1/2 calculated for the high energy density meals were significantly longer than for the standard meals, but there was no significant difference between the tmax values.     

EVALUATION OF RENAL HEMODYNAMICS IN AWAKE AND ISOFLURANE-ANESTHETIZED CATS WITH PULSED-WAVE DOPPLER AND QUANTITATIVE RENAL SCINTIGRAPHY

The feasibility and reproducibility of obtaining the pulsed-wave Doppler measurements of resistive index (RI) and pulsatility index (PI) were investigated in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with isoflurane. In addition, relative renal function and relative renal blood flow were evaluated using quantitative renal scintigraphy. The percentage of injected dose uptake, time to peak activity, and two indices of renal blood flow (K/A ratio and flow index) obtained during the first pass of ^99mTc-MAG₃, were determined for both awake and anesthetized cats. Results indicate that measuring RI and PI in nonsedated cats is readily accomplished and that the results are reproducible within an animal. Mean RI and PI values in the awake cats were 0.55 and 0.8, respectively. Significant differences between the awake and anesthetized cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic measurements evaluated.     

Quantitative detection of atropine-delayed gastric emptying in the horse by the 13C-octanoic acid breath test

The 13C-octanoic acid breath test has been correlated significantly to radioscintigraphy for measurement of gastric emptying indices in healthy horses. The objective of this study was to investigate the validity of the test for measurement of equine delayed gastric emptying, prior to its potential clinical application for this purpose. A model of atropine-induced gastroparesis was used. Gastric emptying rate was measured twice in 8 horses using concurrent radioscintigraphy and/or breath test after treatment i.v. with either atropine (0.035 mg/kg bwt) or saline in randomised order. Analysis of both data sets demonstrated that the atropine treatment had caused a significant delay in gastric emptying rate. Paired breath test data showed an atropine-induced delay in gastric half-emptying time (t 1/2), with no overlap in the 99% CI range (P < 0.001). Significant correlations were found between scintigraphy and 13C-octanoic acid breath test for calculation of both t 1/2 (P < 0.01) and lag phase duration (P < 0.05) in the atropine-delayed emptying results. The mean (s.d.) bias in breath test t 1/2 when compared with scintigraphy was 1.78 (0.58) h. The results demonstrated that the 13C-octanoic acid breath test was an effective diagnostic modality for the measurement of equine delayed gastric emptying. The technique offers advantages to existing methods for clinical investigation, as it is noninvasive, not radioactive, quantitative and requires minimal equipment or training to perform.