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.     

Effect of an indwelling nasogastric tube on gastric emptying rates of liquids in horses

OBJECTIVE: To evaluate the effect of an indwelling nasogastric tube on gastric emptying of liquids in horses. ANIMALS: 9 healthy adult horses. PROCEDURE: A randomized block crossover design was used. For treatment group horses, a nasogastric tube was placed and 18 hours later, acetaminophen was administered; the nasogastric tube remained in place until the experiment was complete. For control group horses, a nasogastric tube was passed into t stomach, acetaminophen was administered, and the nasogastric tube was removed immediately. Serial blood samples were collected 15 minutes before and after administration of acetaminophen. Serum concentration of acetaminophen was determined by use of fluorescence polarization immunoassay. The variables, time to maximum acetaminophen concentration (Tmax) and the appearance constant for acetaminophen (Kapp), were determined. The values for Kapp and Tmax in horses with and without prolonged nasogastric tube placement were compared. RESULTS: No significant difference was found in Kapp between horses with and without prolonged nasogastric tube placement; the median difference in Kapp was 0.01 min(-1) (range, -0.48 to 0.80 min(-1). No significant difference was found in Tmax between horses with and without prolonged nasogastric tube placement; the median difference in Tmax was 5 minutes (range, -30 to 50 minutes). Reanalysis of data following the removal of possible outlier values from 1 horse resulted in a significant difference in Tmax between horses with and without prolonged nasogastric tube placement. CONCLUSIONS AND CLINICAL RELEVANCE: Although no clinically important impact of 18 hours of nasogastric intubation was found on gastric emptying in healthy was found among horses.     

Phenylbutazone prevents the endotoxin-induced delay in gastric emptying in horses.

The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying, and pretreatment with phenylbutazone abolished this effect.     

Yohimbine ameliorates the effects of endotoxin on gastric emptying of the liquid marker acetaminophen in horses.

The effect of yohimbine pretreatment on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses, in horses given endotoxin (E. coli 055 B5; 0.2 microg/kg) intravenously, and in horses given yohimbine (0.25 mg/kg, IV, over 30 minutes) plus endotoxin. Acetaminophen (20 mg/kg) was given by stomach tube 15 minutes after the endotoxin infusion. Blood samples for acetaminophen analysis were collected, and time to reach the peak serum concentration (Tmax), the maximum serum concentration (Cmax) and the area under the acetaminophen serum concentration versus time curve (AUC) were determined for each treatment group. Endotoxin significantly increased Tmax, indicating a profound delay in gastric emptying and yohimbine pretreatment significantly (P < or = 0.05) prevented this effect.     

Metoclopramide ameliorates the effects of endotoxin on gastric emptying of acetaminophen in horses.

The effect of metoclopramide on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses (n = 7), horses given endotoxin intravenously (n = 7), and horses given intravenous metoclopramide plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration vs time curve (AUC) were compared among treatment groups. Endotoxin caused a profound delay in gastric emptying, and pretreatment with metoclopramide significantly (P < 0.05) ameliorated this effect.     

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.     

Determination of solid- and liquid-phase gastric emptying half times in cats by use of nuclear scintigraphy

OBJECTIVE: To use nuclear scintigraphy to establish a range of gastric emptying half times (t1/2) following a liquid or solid meal in nonsedated cats. ANIMALS: 12 clinically normal 3-year-old domestic shorthair cats. PROCEDURE: A test meal of 75 g of scrambled eggs labeled with technetium Tc 99m tin colloid was fed to 10 of the cats, and solid-phase gastric emptying t1/2 were determined by use of nuclear scintigraphy. In a separate experiment, 8 of these cats plus an additional 2 cats were fed 18 ml (n = 5) or 36 ml (n = 5) of a nutrient liquid meal labeled with technetium Tc 99m pentetate. Liquid-phase gastric emptying t1/2 then were determined by use of scintigraphy. RESULTS: Solid-phase gastric emptying t1/2 were between 210 and 769 minutes (median, 330 minutes). Median liquid-phase gastric emptying t1/2 after ingestion of 18 or 36 ml of the test meal were 67 minutes (range, 60 to 96 minutes) and 117 minutes (range, 101 to 170 minutes), respectively. The median t1/2 determined for cats receiving 18 ml of the radiolabeled liquid was significantly less than that determined for cats receiving 36 ml of the test meal. CONCLUSIONS AND CLINICAL RELEVANCE: The protocol was tolerated by nonsedated cats. Solid-phase gastric emptying t1/2 were prolonged, compared with liquid-phase t1/2, and a major factor governing the emptying rate of liquids was the volume consumed. Nuclear scintigraphy may prove useful in assessing gastric motility disorders in cats.     

The Effect of Sedation on Gastric Emptying of a Liquid Marker in Ponies

OBJECTIVE: The effect of sedation on gastric emptying was evaluated in six ponies by monitoring serum concentrations of acetaminophen (AP) after intragastric administration. EXPERIMENTAL DESIGN: Prospective randomized experimental study. ANIMALS: Six adult ponies, 135 to 275 kg. METHODS: Fifteen minutes after the intravenous administration of xylazine (1 mg/kg), butorphanol (0.05 mg/kg), acepromazine (0.05 mg/kg) or saline, ponies were given AP (20 mg/kg in 350 mL water) by stomach tube. Blood for AP analysis was collected at baseline and 15, 30, 45, 75, 90, 105, and 120 minutes after AP administration. The time (Tmax) to reach peak serum concentration (Cmax), and the area under the AP serum concentration versus time curve (AUC) were determined for each treatment group. RESULTS: Tmax was 31 mins in the control group, and this increased significantly (P<.05) after sedation. Cmax decreased (P<.05) after xylazine administration, and AUC decreased (P<.05) after acepromazine. CONCLUSIONS: This study indicated that sedation has a significant effect on the gastric emptying rate of a liquid in ponies.     

Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses

Objective-To determine the effect of ranitidine on gastric emptying in horses. Animals-11 adult horses. Procedures-In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study. Results-Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10(4) M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups. Conclusions and Clinical Relevance-Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying.     

Effect of erythromycin and gentamicin on abomasal emptying rate in suckling calves

BACKGROUND: Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying. HYPOTHESIS: Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying. ANIMALS: Five male Holstein-Friesian calves (8-15 days of age). METHODS: Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low-dose gentamicin, 4.4 mg/kg; high-dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actual C(max)) and time of actual C(max) (actual T(max)) were determined, and pharmacokinetic modeling was used to calculate model C(max) and model T(max). RESULTS: Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actual T(max) and model T(max) (P < .05). Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control. Administration of high-dose gentamicin resulted in a longer time to actual T(max) (P= .021) but did not change model T(max) (P= .62). CONCLUSIONS AND CLINICAL RELEVANCE: IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.     

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.     

GASTRIC EMPTYING IN CATS USING FOODS VARYING IN FIBER CONTENT AND KIBBLE SHAPES

The purpose of this study is to evaluate the influence of kibble shape and fiber content of commercial dry foods on gastric emptying in healthy cats. Eight healthy cats were used to evaluate four different diets which varied in shape of kibble (round versus triangle) or fiber content (low versus high). Diets were labeled with 99mTc-mebrofenin and gastric emptying was evaluated with nuclear scintigraphy. There was a significant difference between the kibble shapes at both T50 and T20. The triangle shaped kibble required significantly longer time than the round kibble to reach T50 (P = 0.02) and T20 (P = 0.001). Diet fiber content did not have a significant influence on T50, and T20. The influence of caloric and water intake was assessed with division of cats into high, medium, and low intake groups. The caloric intake had its main effect at T50 with the lowest quartile of caloric intake requiring significantly less time to reach T50 than the middle group and upper quartile (P = 0.05). Water intake did not have a significant effect on gastric emptying in this study. There was no relationship or correlation between the surface area of the food (cm2/kg) and T90, T50, and T20.     

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.     

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.     

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.     

Oral pharmacokinetics of acetaminophen to evaluate gastric emptying profiles of Shiba goats

The pharmacokinetics of acetaminophen was investigated following oral dosing to Shiba goats in order to evaluate the properties of gastric emptying. Acetaminophen was intravenously and orally administered at 30 mg/kg body weight to goats using a crossover design with a 3-week washout period. The stability of acetaminophen in rumen juice was also assessed. Acetaminophen concentrations were measured by HPLC. Since acetaminophen was stable in rumen juice for 24 hr, the extremely low bioavailability (16%) was attributed to its hepatic extensive first-pass effect. The mean absorption time and absorption half-life were unexpectedly short (4.93 and 3.35 hr, respectively), indicating its marked absorption from the forestomach, which may have been due to its smaller molecular weight. Therefore, acetaminophen was considered to be unsuitable for evaluating gastric emptying in Shiba goats.     

THE SCINTIGRAPHIC EVALUATION OF SOLID PHASE GASTRIC EMPTYING IN NORMAL CATS

The gastric emptying half-time of solid food in normal cats was determined using a scintigraphic technique. ^99mTc-sulfur colloid was applied to dry food. Sequential images were acquired post prandial, and the gastric emptying half-time was determined for several different acquisition and processing parameters. Good correlation was found between different acquisition and processing methods, some of which made use of edge detection applications, while others used different views, or number of views from which the gastric emptying half-time was calculated. The mean ± standard deviation, (range) and median of the gastric emptying half-time determined using the geometric mean of total counts in hand-drawn regions of interest from the lateral and ventral images were 2.47 × 0.71, (1.42–3.61) and 2.37 hours respectably.     

Pulmonary distribution of aerosolized technetium Tc 99m pentetate after administration of a single dose of aerosolized albuterol sulfate in horses with recurrent airway obstruction.

OBJECTIVE: To determine whether pulmonary distribution of aerosolized technetium Tc 99m pentetate is improved after inhalation of a single dose of albuterol sulfate in horses susceptible to recurrent airway obstruction (heaves). ANIMALS: 6 horses with heaves and 4 horses with normal respiratory tract function. PROCEDURE: Images were obtained during ventilation of horses at baseline (maximal change in pleural pressure during tidal breathing [deltaPpImax] >15 cm H2O) and after aerosolized albuterol sulfate (360 microg) administration, with a 24-hour washout period between experiments. The deltaPpImax was determined prior to the baseline scan, prior to albuterol sulfate administration, and 5 minutes after albuterol sulfate administration. Images were assessed by visual inspection (semi-quantitative scoring system) and histogram analysis. RESULTS: Images obtained from horses with heaves had nonuniform pulmonary distribution of radionuclide characterized by poor penetration in peripheral lung fields and excess deposition in large airways. Histogram analysis of images of the caudal portions of the lungs revealed nonuniform radionuclide deposition in horses with heaves and uniform radionuclide deposition in control horses. CONCLUSION: Administration of a single dose of aerosolized albuterol sulfate improved pulmonary distribution of aerosolized radiolabeled pentetate suspension in horses with heaves but did not alter pulmonary distribution in clinically normal horses. CLINICAL RELEVANCE: Precedent bronchodilator administration may improve pulmonary distribution of aerosolized, surface-active anti-inflammatory preparations.     

Use of plasma clearance of technetium Tc 99m pentetate to estimate renal clearance during postnatal development in pigs

OBJECTIVE: To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. Animals: 24 female pigs. Procedure: At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetiumTc 99m pentetate was calculated. Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance (r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. CONCLUSIONS: Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple biood samples in pigs from 3 to 24 weeks of age.