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.     

Neostigmine methylsulfate delays gastric emptying of particulate markers in horses

Eight horses were allotted to 2 groups, each of 4 horses. All horses were given 100 plastic markers intragastrically via a nasogastric tube. One group of animals (control group) was not given medication after marker administration. The other group (test group) was given neostigmine methylsulfate (0.022 mg/kg of body weight) in the subcutaneous tissue at the time of marker administration and 30, 60, and 90 minutes later. All horses were killed 135 minutes after marker administration to locate the beads in the gastrointestinal tract. Gastric emptying of the markers was significantly delayed (P less than 0.05) in horses given neostigmine methylsulfate.     

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.     

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.     

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.     

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.     

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.     

Meal-induced gastric relaxation and emptying in horses after ingestion of high-fat versus high-carbohydrate diets

OBJECTIVE: To evaluate the effect of ingestion of a high-carbohydrate versus a high-fat meal on relaxation of the proximal portion of the stomach and subsequent gastric emptying in horses. ANIMALS: 6 healthy adult horses. PROCEDURE: The study consisted of 2 phases. In phase I, horses were offered a high-fat (8% fat) or a high-carbohydrate (3% fat) pelleted meal (0.5 g/kg) of identical volume, caloric density, and protein content. In phase II, meals consisted of a commercial sweet feed meal (0.5 g/kg) or this meal supplemented with corn oil (12.3% fat) or an isocaloric amount of glucose (2.9% fat). Proximal gastric tone was measured by variations in volume of an intragastric bag introduced through a gastric cannula and maintained with a constant internal pressure by an electronic barostat. Rate of gastric emptying was measured simultaneously with the 13C-octanoic acid breath test. Interaction between both techniques was studied in additional experiments. RESULTS: Meals with higher carbohydrate content induced a significantly more prolonged receptive relaxation of the proximal portion of the stomach than those with higher fat content, but the accommodation response was similar. Labeling the meals with the breath test marker influenced the accommodation response measured by the barostat. Gastric emptying rates were not significantly different between meals, although those high in carbohydrate initially emptied more slowly. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, in contrast to most species, dietary fat supplementation may not have a profound effect on gastric motility.     

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.     

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.     

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.     

Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses

Endotoxemia causes significant mortality and morbidity in horses. The mechanisms underlying this complex pathophysiology remain unclear. Therefore, effective tools to treat endotoxemia in horses are lacking. Furthermore, the multifactorial and multiorgan pathophysiology of equine endotoxemia has not been fully addressed, especially the lung injury associated with endotoxemia. Within the context of the broader picture of endotoxemia and lung injury, we offer a perspective on the roles of pulmonary intravascular macrophages in endotoxin-induced lung inflammation in horses.     

Prevalence of gastric ulcers in show horses.

OBJECTIVE: To determine prevalence and risk factors for gastric ulcers in show horses. DESIGN: Field survey. ANIMALS: 50 horses in active training that had been transported to at least 1 event in the 30 days prior to endoscopy. PROCEDURE: Interview of owner, physical examination, serum biochemical analysis, CBC, and gastric endoscopy were performed. RESULTS: Gastric ulceration was detected in 58% of the horses. Horses with a nervous disposition were more likely to have ulceration than quiet or behaviorally normal horses. Horses with gastric ulceration had significantly lower RBC counts and hemoglobin concentrations than those without ulceration. CONCLUSIONS AND CLINICAL RELEVANCE: Show horses have a high prevalence of gastric ulceration. Lower RBC counts and hemoglobin concentrations may be the result of chronic gastric ulceration.     

Phenylbutazone and the horse--a review.

The clinical uses and side-effects of phenylbutazone in man, horses, and other animals are reviewed. The blood dyscrasias commonly described in man have not been reported in the horse, although several of the more minor side-effects have occasionally been seen (e.g. water retention, depression, transient staggering and phlebitis). Despite the lack of documented evidence, the toxicity of phenylbutazone in the horse is considered to be lower than that in man. This may be associated with the lower dose rates normally used, the more rapid plasma clearance rate and the comparatively younger age of most horses under treatment. The following guidelines for the use of phenylbutazone in practice are put toward. It should only be used under strict veterinary control and then only if there are clear clinical indications. It should not be given if there are signs of gastro-intestinal ulceration, clotting defects or any cardiac, renal or hepatic dysfunction. Dose rates should be kept to a minimum and the drug withdrawn immediately if any side-effects occur or if there is no clinical response within 4 days. If prolonged therapy is necessary, periodic haematological analyses should be carried out.     

Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses

OBJECTIVE: To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. ANIMALS: 6 healthy adult Thoroughbreds. PROCEDURES: Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT 1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 microg/kg/min for 30 minutes) to establish an effective GR55562 dose. In a crossover study, horses were treated with IV administration of saline solution (control treatment), aspirin (4 mg/kg, 2 hours or 4 days before lipopolysaccharide [LPS] infusion), GR55562 (0.3 mg/kg), the PAF antagonist WEB2086 (3 mg/kg), or aspirin plus GR55562 prior to LPS infusion (30 ng/kg for 30 minutes). Digital blood flow was measured by use of Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures were made. Serial blood samples were collected and plasma 5-HT and TxA2 concentrations determined. RESULTS: GR55562 abolished tryptamine-induced digital hypoperfusion. Neither WEB2086 nor GR55562 affected LPS-induced alterations in digital perfusion or plasma mediator concentrations. Aspirin given 2 hours before LPS administration abolished the increase in plasma TxA2 concentration and significantly attenuated LPS-induced digital hypoperfusion. Aspirin given 4 days before LPS significantly attenuated the increase in plasma TxA2 concentration and digital hypothermia. Aspirin plus GR55562 had a greater effect on LPS-induced digital hypothermia than aspirin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Thromboxane A2 and 5-HT played a role in mediating LPS-induced digital hypoperfusion in horses. Platelet-activating factor appeared unimportant in mediating LPS-induced 5-HT or TxA2 release or digital hypoperfusion.     

Ureteral ligation prevents the haemodynamic effect of frusemide in pentobarbitol anaesthetised horses

Frusemide reduces pulmonary vascular pressures in resting horses and attenuates exercise-induced increases in these pressures in exercising horses. The mechanism underlying these effects of frusemide is unclear. We tested the hypothesis that the haemodynamic effects of frusemide are dependent on diuresis by examining the effect of frusemide in anaesthetised horses in which diuresis was prevented by ligation of ureters. Twenty four horses were assigned randomly to one of 4 treatments: 1) frusemide (1 mg/kg bwt i.v.) and intact ureters; 2) frusemide and ligated ureters; 3) saline placebo and ligated ureters; and 4) frusemide and phenylbutazone (4.4 mg/kg bwt i.v. 12 h and 15 min before frusemide) and ligated ureters. Frusemide administration to anaesthetised horses with intact ureters increased plasma total protein concentration and reduced mean right atrial, pulmonary artery and aortic pressures. There was no significant effect of frusemide administration on haemodynamic variables or plasma total protein concentration in horses with ligated ureters. The combination of frusemide and phenylbutazone increased mean right atrial, pulmonary artery and aortic pressures in horses with ligated ureters. This study demonstrates that, in anaesthetised horses, the haemodynamic effect of frusemide is dependent upon diuresis. We interpret these results as providing further evidence that the haemodynamic effect of frusemide in horses is attributable to a reduction in plasma and blood volume.