Evaluation of a long‐acting injectable formulation of omeprazole in healthy dogs

BackgroundTo evaluate the efficacy of a single intramuscular adminsitration of long‐acting omeprazole (LA‐OMEP) in increasing gastric pH in dogs.HypothesisWe hypothesized that LA‐OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration.AnimalsNine healthy research dogs.MethodsProspective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA‐OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined.ResultsThe mean onset of action for the LA‐OMEP was 98.11 min (SD 46.39). The mean number of days the dogs'' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3‐7) and 5.25 days for MPT pH ≥4 (range, 3‐7). Long‐acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs.Conclusions and Clinical ImportanceThe LA‐OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed.     

Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy

BACKGROUND: Thrombosis and arterial thromboembolism are frequent complications of feline cardiomyopathy, especially when associated with left atrial enlargement. Markers of activated coagulation may be used to evaluate the coagulation status of cats with hypertrophic cardiomyopathy (HCM) in relation to left atrial size. OBJECTIVES: The objective of this study was to compare plasma concentrations of thrombin-antithrombin complex (TAT), D-dimer, and fibrin degradation products (FDP) between clinically healthy cats and cats with HCM. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and antithrombin activity were also compared and the association between left atrial (LA) size and coagulation results in cats with HCM was evaluated. METHODS: Blood samples from 19 clinically healthy cats and 20 cats with HCM were obtained. All cats with HCM were asymptomatic and had no signs of heart failure. LA diameter and LA to proximal aortic (Ao) diameter ratio (LA:Ao) were determined by echocardiography. RESULTS: Reference intervals for D-dimer and TAT concentrations in plasma of healthy cats were established as 0.09-0.32 microg/mL and 2.0-20.0 microg/L, respectively. TAT, D-dimer, and FDP concentrations were increased in 5, 3, and 2 cats with HCM, respectively. TAT and D-dimer concentrations, and PT and aPTT were not significantly different between groups. Antithrombin activity was significantly decreased in cats with HCM (P=.03) despite marked range overlap. LA and LA:Ao were not correlated with coagulation results. CONCLUSIONS: Laboratory evidence of hypercoagulability was found in 45% of cats with HCM. Left atrial size was not associated with laboratory evidence of hypercoagulability. Association between coagulation markers and risk of thrombosis has yet to be evaluated in cats with HCM.     

Platelet function in clinically healthy cats and cats with hypertrophic cardiomyopathy: analysis using the Platelet Function Analyzer‐100

Background: There is currently no simple analytical tool for the evaluation of hypercoagulability in cats. The Platelet Function Analyzer‐100^® (PFA‐100; Dade Behring Inc., Deerfield, IL, USA) is a bench‐top machine that evaluates platelet function by measuring closure time (CT) in citrated whole blood under high shear conditions. We hypothesized that cats with hypertrophic cardiomyopathy (HCM) have up‐regulated platelet function, which shortens their CT and increases their risk for thromboembolic events. Objectives: The goals of this study were to: (1) establish a feline reference interval for CT using the PFA‐100, (2) measure CT in blood from cats with HCM, and (3) determine if there is a measurable difference between the CT of healthy cats compared with cats with HCM. Methods: Citrated blood samples from 42 clinically healthy cats and 30 cats with HCM were analyzed according to manufacturer's specifications. CT was measured in triplicate and the mean value was used for analysis. Transformed data were compared between clinically healthy cats and cats with HCM using a Student's t‐test, and among cats with mild, moderate, or severe HCM using ANOVA. Results: The median CT of clinically healthy cats was 64 seconds (range 43–176 seconds). The median CT of cats with HCM was 74 seconds (range 48–197 seconds). There was no significant difference in CT between cats with HCM and clinically healthy cats. There also were no significant differences in cats with mild, moderate, or severe HCM. Conclusions: A feline reference interval for PFA‐100 CT will be useful in future studies of platelet function in cats. Cats with HCM do not have shorter CTs when compared with clinically healthy cats.     

Triple phase computed tomography of the pancreas in healthy cats

While the availability and use of computed tomography (CT) continues to grow, no study has described the size and multiphase CT appearance of the normal feline pancreas. This information is important to not only allow more accurate identification and differentiation of disease, but it may also be useful in assessing pancreatic function. In this prospective analytical study, we described a triple phase CT protocol of the pancreas for use in sedated cats and the attenuation, enhancement pattern, size, and volume of the pancreas for a group of healthy cats. Fifteen healthy cats were enrolled in the study and a standardized protocol for acquiring arterial, portal, and delayed phase CT images of the pancreas was developed and described. The pancreas was hypo to isoattenuating to both the liver and spleen in all phases in the majority of cats with a homogenous enhancement pattern noted in all 15. Mean pancreatic attenuation was 48, 79, 166, and 126 Hounsfield units (HU) respectively on precontrast, arterial, portal, and delayed phase images. In addition, mean height, length, and width of the left lobe of the pancreas were larger than the right lobe in all 15 cats. There were no associations between volume and volume: body weight ratio with age (P = 0.6518, P = 0.6968) or sex (P = 0.7013, P = 0.2043). This baseline information may be beneficial for use in future studies characterizing pancreatic disease in cats as well as future research studies evaluating pancreatic endocrine function.     

Effect of age, feeding, and omeprazole administration on gastric tonometry in healthy neonatal foals

BACKGROUND: Gastric tonometry is commonly used in humans as an assessment of intestinal mucosal perfusion. Values in healthy foals are currently unknown. HYPOTHESIS: Age, enteral feeding, and omeprazole administration would significantly alter gastric tonometry measurements in neonatal foals. ANIMALS: Nine clinically normal foals were used to assess the effect of age and feeding, and 8 similar foals were used to assess the effect of omeprazole. METHODS: At 1, 7, and 14 days of age, gastric intramucosal PCO2 (PgCO2) and arterial blood gas samples were obtained at baseline, immediately after feeding milk, and 1 and 2 hours after fasting for calculation of the intramucosal-arterial PCO2 difference (DeltaCO2). To evaluate the effect of omeprazole, foals were evaluated twice as above, 2 hours after fasting, comparing administration of omeprazole to no drug. RESULTS: There was a significant effect of age and feeding on PgCO2 and DeltaCO2, whereas arterial PCO2 was not significantly affected by these factors. Postfeeding DeltaCO2 values were significantly lower than fasted values. Baseline and postfeeding DeltaCO2 increased with age. There was no significant effect of age on data collected after 1 or 2 hours of fasting. The 90% reference interval for DeltaCO2 data collected after fasting was 0-54 mmHg. Foals had a significantly higher mean gastric pH and significantly higher DeltaCO2 and PgCO2 following omeprazole relative to no treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Because of the high and variable DeltaCO2, which is exacerbated by omeprazole administration, the reference interval in foals is extremely wide.     

The effect of dorzolamide 2% on circadian intraocular pressure in cats with primary congenital glaucoma

Objective To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats. Animals studied Seven adult cats with primary congenital glaucoma (PCG). Procedures Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12‐h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons. Results Estimated mean IOP for the reference time point pre‐treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2–6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU). Conclusions Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG.     

Effects of oral orbifloxacin on fecal coliforms in healthy cats: a pilot study

The study objective was to determine the effect of oral orbifloxacin (ORB) onantimicrobial susceptibility and composition of fecal coliforms in cats. Nine cats wererandomized to two groups administered a daily oral dose of 2.5 and 5.0 mg ORB/kg for 7days and a control group (three cats per group). Coliforms were isolated from stoolsamples and were tested for susceptibilities to ORB and 5 other drugs. ORB concentrationin feces was measured using high-performance liquid chromatography (HPLC). The coliformswere undetectable after 2 days of ORB administration, and their number increased in mostcats after termination of the administration. Furthermore, only isolates ofEscherichia coli were detected in all cats before administration, andthose of Citrobacter freundii were detected after termination of theadministration. E. coli isolates exhibited high ORB susceptibility[Minimum inhibitory concentration (MIC), ≤0.125 µg/ml]or relatively low susceptibility (MIC, 1−2 µg/ml) with asingle gyrA mutation. C. freundii isolates largelyexhibited intermediate ORB susceptibility (MIC, 4µg/ml), in addition to resistance to ampicillin andcefazolin, and harbored qnrB, but not a gyrA mutation.HPLC revealed that the peaks of mean concentration were 61.3 and 141.0µg/g in groups receiving 2.5 and 5.0 mg/kg, respectively. Our findingssuggest that oral ORB may alter the total counts and composition of fecal coliform, but isunlikely to yield highly fluoroquinolone-resistant mutants of E. coli andC. freundii in cats, possibly because of the high drug concentration infeces.     

Estimation of glomerular filtration rate in healthy cats using single-slice dynamic CT and Patlak plot analysis

Commonly used clinical indicators of renal disease are either insensitive to early dysfunction or have delayed results. Decreased glomerular filtration rate (GFR) indicates renal dysfunction before there is a loss of 50% of functional nephrons. Most tests evaluate global rather than individual kidney function. Dynamic computed tomography (CT) and Patlak plot analysis allows for individual GFR to be tested. Our objectives were to establish a procedure and provide reference values for determination of global GFR in 10 healthy cats using dynamic CT (CTGFR). This method of GFR determination was compared against serum iohexol clearance (SIC). A single CT slice centered on both kidneys and the aorta was acquired every fifth second during and after a bolus injection of iohexol (240 mgI/ml; 300 mgI/kg) for 115 s. Using data from this dynamic acquisition, Patlak plots were obtained, GFR was calculated, and results were compared to global GFR determined by iohexol clearance. The average global CTGFR estimate was 1.84 ml/min x kg (SD = 0.43; range = [1.22, 2.45]). The average global GFR measured using SIC was 2.45 ml/min x kg (SD = 0.58; range = [1.72, 3.69]). GFR measurements estimated by both dynamic CT and SIC were positively associated (estimated Spearman rank correlation coefficient = 0.72; P = 0.0234). The CTGFR method consistently underestimated GFR with a bias of -0.62 (SE = 0.1307) when compared to SIC (P = 0.0011). In healthy cats, CTGFR was capable of determining individual kidney function and appears clinically promising.