Pharmacokinetics and anti-nausea effects of intravenous ondansetron in hospitalized dogs exhibiting clinical signs of nausea.

The purpose of this study was to evaluate the pharmacokinetics of intravenous (IV) ondansetron in a population of hospitalized dogs exhibiting clinical signs of nausea. The causes of nausea included pancreatitis, gastroenteritis, endocarditis, chemotherapy-induced nausea, diabetes mellitus and ketoacidosis, acute kidney injury with aspiration pneumonia, pyometra, uroabdomen, neoplasia, and hepatopathy. Twenty-four dogs were randomly assigned to one of the following IV ondansetron protocols: 1 mg/kg q12h, 0.5 mg/kg q12h, 1 mg/kg q8h, 0.5 mg/kg q8h. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after the first dose, and nausea scores were recorded at multiple time points. Ondansetron and arginine vasopressin (AVP) concentrations were measured via high-performance liquid chromatography coupled to tandem mass spectrometry and ELISA, respectively. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Ondansetron displayed linear pharmacokinetics. In the 0.5 mg/kg group, mean Cmax  = 214 ng/ml, AUC0-8h  = 463 ng/ml*h, and calculated half-life was 1.9 h. In the 1 mg/kg group, mean Cmax  = 541 ng/ml, AUC0-8h  = 1057 ng/ml*h and calculated half-life was 1.6 h. Serum ondansetron concentrations were not significantly different between dogs that required rescue anti-nausea medication (non-responders) and dogs that did not require rescue therapy (responders). In total, 83.3% of patients in the 0.5 mg/kg q8h, 0.5 mg/kg q12h, and 1 mg/kg q8h groups had improvement in nausea scores. In total, 66.7% of patients in the 1 mg/kg q12h group had improvement in nausea scores. In total, 33% of patients had resolution of nausea in the 0.5 mg/kg q8h, 1 mg/kg q8h, and 1 mg/kg q12h groups, and 16% of patients had resolution of nausea in the 0.5 mg/kg q12h group. AVP concentrations were highly variable and did not correlate with nausea scores. Nausea scores significantly decreased regardless of dosage protocol. AVP was not a reliable biomarker of nausea in this group of dogs.

Plasma Concentrations of Oral Ondansetron in Hospitalized Dogs Exhibiting Clinical Signs of Nausea.

The purpose of this study was to evaluate plasma ondansetron (OND) concentrations in a population of dogs with naturally occurring nausea after oral OND administration. Twenty-four dogs were randomly assigned to receive one of the following doses of oral OND: 0.5 mg/kg q8h, 0.5 mg/kg q12h, 1 mg/kg q8h, or 1 mg/kg q12h. Blood samples for plasma OND measurements were collected at baseline and 2, 4, and 8 h after administration of the first dose of OND. OND concentrations averaged over an 8 h time period were not significantly different between dose groups (0.5 mg/kg group: median 8.5 ng/mL [range 1-96.8 ng/mL], 1 mg/kg group: median 7.4 ng/mL [range 1-278.7 ng/mL]). The mean maximum concentrations in the 0.5 mg/kg and 1 mg/kg groups were 35.8 ± 49.0 ng/mL and 63.3 ± 121.1 ng/mL, respectively. OND concentrations were below the lower limit of quantification (LLOQ) in 50% (18/36) of samples in the 0.5 mg/kg groups and 39% (14/36) of samples in the 1 mg/kg groups. Six dogs (6/24, 25%) did not have OND detected at any time. The mean nausea scores at baseline were similar amongst all groups and decreased over time. The bioavailability of oral OND appears to be poor. Despite low plasma OND concentrations, nausea scores improved over time.

Association between feline hyperthyroidism and thoracic radiographic evaluation of cardiomegaly and pulmonary hyperinflation.

OBJECTIVES: Hyperthyroidism frequently affects middle-to-older-aged cats that can present with cardiorespiratory signs. The effects of hyperthyroidism on cardiac size and function have been previously documented. Anecdotally, pulmonary hyperinflation identified on thoracic radiographs may also be associated with hyperthyroidism; however, there is no literature to support this claim. The goal of this study was to determine any association between hyperthyroidism, pulmonary hyperinflation and cardiomegaly with the following hypotheses: (1) hyperthyroid cats would not have evidence of radiographic pulmonary hyperinflation compared with control cats; and (2) hyperthyroid cats were more likely to have evidence of radiographic cardiomegaly than control cats. METHODS: In this retrospective case-control study, the thoracic radiographs of 52 hyperthyroid cats and 46 non-hyperthyroid cats were evaluated for subjective and objective measurements of pulmonary hyperinflation and cardiomegaly. RESULTS: There were no statistically significant differences between hyperthyroid and non-hyperthyroid cats for any variable indicative of pulmonary hyperinflation. The mean ± SD vertebral heart score on lateral views for hyperthyroid cats was 7.75 ± 0.53 and for control cats was 7.55 ± 0.54, which was significantly different (P = 0.05). Among all cats, a more severe total elevation in thyroxine (T4) was correlated with a larger vertebral heart score on lateral views (Spearman's correlation coefficient = 0.23, P = 0.02). CONCLUSIONS AND RELEVANCE: While the results of this study suggest that hyperthyroid cats are more likely to have a larger vertebral heart score on lateral views than control cats, the clinical relevance of this finding is unclear given the large degree of overlap between hyperthyroid and non-hyperthyroid cats. In addition, among all cats, a greater total T4 elevation was weakly correlated with a larger vertebral heart score. Hyperthyroidism is not associated with radiographic pulmonary hyperinflation and is an unlikely differential for this radiographic finding.

Coagulation status, fibrinolysis, and platelet dynamics in dogs with chronic inflammatory enteropathy.

BACKGROUND: Coagulation status is poorly understood in dogs with chronic inflammatory enteropathy (CIE). Fibrinolytic activity and platelet dynamics have not been evaluated in CIE dogs. OBJECTIVES: To assess coagulation status and fibrinolysis in normoalbuminemic CIE dogs (CIE-N) and CIE dogs with protein-losing enteropathy (CIE-PLE) compared to healthy controls (HC). To evaluate thromboelastography (TEG) variable differences between groups and for correlations with clinicopathologic data. To report platelet dynamics in CIE dogs. ANIMALS: Twenty-five client-owned dogs with CIE (n = 16 CIE-N; n = 9 CIE-PLE); 14 HC beagle dogs. METHODS: All dogs had tissue factor + tissue plasminogen activator TEG. Nine of 25 CIE dogs had whole blood impedance platelet aggregometry. The TEG variables and coagulation data were compared between all CIE vs HC dogs, CIE-N dogs vs HC, and CIE-PLE dogs vs HC. Clinicopathologic and coagulation data were available for CIE dogs and assessed for correlation to TEG variables. RESULTS: Dogs with CIE had higher maximum amplitude (MA; P < .001), longer clot lysis times (CLTs; P < .001), lower % lysis after 30 minutes (LY30; P < .001), and % lysis after 60 minutes (LY60; P < .001) compared to HC, suggesting hypercoagulability and hypofibrinolysis. When separated out, both CIE-N and CIE-PLE dogs had higher MA, longer CLT, and lower LY30 and LY60 compared to HC. Serum albumin and 25-hydroxyvitamin D (25[OH]D) concentrations, and plasma antithrombin and fibrinogen concentrations moderately correlated with MA. CONCLUSIONS AND CLINICAL IMPORTANCE: Normoalbuminemic and hypoalbuminemic CIE dogs were considered hypercoagulable based on TEG compared to HC. Some CIE dogs displayed hypofibrinolytic phenotypes on TEG.

Evaluation of platelet function in cats with and without kidney disease: a pilot study.

OBJECTIVES: The aims of this study were to determine if stable chronic kidney disease (CKD) cats and uremic crisis cats have altered platelet function, and to determine the prevalence of positive fecal occult blood in CKD cats. METHODS: Platelet function in normal cats, clinically stable International Renal Interest Society (IRIS) stage 2-4 CKD cats and CKD cats experiencing a uremic crisis were evaluated using impedance aggregometry. Area under the curve (AUC) at 6 mins was calculated for saline, adenosine diphosphate (AUCADP) and arachidonic acid (AUCASPI). The AUC in addition to hematocrit, platelet count and mean platelet volume (MPV) were compared between groups using the Kruskal-Wallis test followed by Dunn's post-hoc analysis. Guaiac fecal occult blood tests were performed on fecal samples and results were compared between groups using a χ2 for trend test. RESULTS: AUCADP (P = 0.04) and AUCASPI (P = 0.05) were significantly higher in uremic crisis cats compared with normal cats at 6 mins. Hematocrit was significantly higher in normal cats when compared with IRIS stage 3 and 4 (P = 0.002) and uremic crisis (P = 0.0008) cats, with no difference among groups for platelet count or MPV. The proportion of cats with positive fecal occult blood samples was significantly different between groups (P = 0.0017); 50% uremic crisis cats, 33% IRIS stage 3 and 4 cats, and 10% IRIS stage 2 cats were positive, while no normal cats were positive. The proportion of cats with platelet clumping was significantly different between groups (P = 0.03). CONCLUSIONS AND RELEVANCE: Platelet hyper-reactivity may be occurring in CKD cats experiencing a uremic crisis. The etiology of positive fecal occult blood samples in CKD cats is unclear and did not appear to be related to decreased platelet function as measured in this study and requires further investigation.

Ehrlichia canis in dogs experimentally infected, treated, and then immune suppressed during the acute or subclinical phases.

BACKGROUND: Concerns for recrudescence of Ehrlichia canis infection arise when immunosuppressive drugs are used to treat immune-mediated diseases in dogs previously infected with E. canis. OBJECTIVES: Determine whether administration of prednisolone and cyclosporine would reactivate E. canis infection in dogs previously treated with doxycycline during the acute or subclinical phases. ANIMALS: Seven beagles previously experimentally infected with E. canis and administered doxycycline for 4 weeks were included. Three of the 7 dogs were incidentally concurrently infected with Anaplasma platys and Babesia vogeli and were administered 2 doses of imidocarb 2 weeks apart before enrollment in the current study. METHODS: Experimental study. Each dog was administered prednisolone and cyclosporine for 6 weeks. Clinical signs, complete blood cell count (CBC), polymerase chain reaction (PCR) assays for E. canis, A. platys, and B. vogeli DNA in blood, E. canis indirect fluorescent antibodies (IFA) titers, and flow cytometry for antiplatelet antibodies were monitored. RESULTS: All dogs completed the immunosuppressive protocol. No evidence for recrudescence of E. canis, A. platys, or B. vogeli were detected based on clinical signs or results of CBC, PCR, IFA, and flow cytometry for antiplatelet antibodies. E. canis IFA titers were negative in 5/7 dogs at the end of immunosuppressive protocol and were negative 6 months after the protocol in 5/5 dogs available for testing. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs administered with a 4-week course of doxycycline with or without imidocarb failed to show evidence of activation of E. canis infection after administration of a commonly used immune suppressive protocol.

Effects of storage conditions on two platelet agonists for whole blood impedance platelet aggregometry in dogs.

BACKGROUND: Whole blood impedance platelet aggregometry (Multiplate-) can be performed with different agonists to evaluate platelet function. Although the manufacturer recommends disposal of stored reagents after 1 month at -20°C or 24 hours at 4°C, reagent integrity after reconstitution under different storage conditions is unknown. If reagent integrity is stable for longer periods, assay costs could decrease dramatically. OBJECTIVES: This study aimed to determine the stability of reconstituted arachidonic acid (AA) and adenosine diphosphate (ADP) platelet agonists stored at -20°C and -80°C for up to 6 months. METHODS: Aliquots of reconstituted AA and ADP were stored at -20°C and -80°C each month for a total of 6 months. Six healthy staff-owned dogs were enrolled in the study. A physical examination, CBC, diagnostic panel, urinalysis, and baseline platelet aggregometry assessment was performed on all of the dogs. Platelet aggregometry was performed using fresh and stored aliquots of AA and ADP reagents on the same day. The area under the curve (AUC) was recorded from each platelet aggregometry analysis. Repeated measures (RM) analysis (one-way ANOVA) was performed and subsequent time points (1, 2, 3, 4, 5, and 6 months) were compared with fresh AUC results. RESULTS: All dogs were clinically healthy, and all diagnostic tests were normal. There were no differences in AUC obtained from fresh samples at any time point or either temperature for AA or ADP. CONCLUSIONS: Whole blood impedance platelet aggregometry reagents, AA and ADP, were stable for up to 6 months when stored at -20°C or -80°C, obviating the need to discard viable reagents, and decreasing assay costs.

Variability of tissue factor-activated thromboelastography and whole blood impedance platelet aggregometry in healthy dogs.

OBJECTIVE: To assess interindividual (CVG ) and intraindividual (CVI ) variability over time for results of thromboelastography (TEG) and whole-blood impedance platelet aggregometry in healthy dogs. ANIMALS: Six healthy Beagle dogs. MEASUREMENTS AND MAIN RESULTS: Tissue factor (TF)-activated TEG and adenosine diphosphate (ADP) and arachidonic acid (AA)-induced whole blood impedance platelet aggregometry were performed at 3 different time points (days 1, 4, and 6). In addition, platelet count, hematocrit, and plasma fibrinogen concentrations were recorded each study day. Activated partial thromboplastin time, one-stage prothrombin time, antithrombin activity, and D-dimer concentrations were measured on the first day of the study. For TEG, the variables reaction time (R), clotting time (K), rate of clot formation (α), and maximum amplitude (MA) were recorded. For platelet aggregometry, the areas under the curve for ADP (AUCADP )- and AA (AUCAA )-induced aggregation were measured. The CVI was lower than the CVG over time for MA, AUCADP , and AUCAA ; however, the CVI was higher than the CVG for the TEG variables R, K, and α. There were no statistical differences in the platelet count, hematocrit, and fibrinogen measurements over time. CONCLUSIONS: In healthy dogs, a subject-based reference interval for ADP- and AA-induced platelet aggregometry and the TEG variable MA provide a more sensitive method to detect changes. However, due to the high CVI , population-based reference intervals may be more appropriate for interpretation of the TEG variables R, K, and α.

Urine Cytology: Collection, Film Preparation, and Evaluation.

Cytologic examination of the urine sediment in animals suspected of having urinary tract disease or lower urinary tract masses is one of the best means of distinguishing inflammation, infection, and neoplasia and can help determine if a positive dipstick result for hemoglobin/blood is due to hemorrhage or blood contamination. The quality of the specimen collection and handling plays an important role in the quality of results, the validity of interpretations, and selection of appropriate course of action. The method of sample collection aids localization of pathology. Air dry but do not heat fix, freeze, or expose films to formalin fumes, temperature extremes, or condensation.

Evaluation of the Leptospira species microscopic agglutination test in experimentally vaccinated cats and Leptospira species seropositivity in aged azotemic client-owned cats.

OBJECTIVES: The objectives of this study were to validate the microscopic agglutination test (MAT) using feline sera, determine cross-reactivity of Borrelia burgdorferi antibodies in the MAT, and evaluate if there is an association between Leptospira species seropositivity in aged (⩾10 years) client-owned cats with and without azotemia (creatinine >2 g/dl). METHODS: A four-serovar canine leptospiral vaccine was administered to two specific pathogen-free (SPF) cats on days 0 and 14. The MAT was performed intermittently until day 42 for the serovars Canicola, Grippotyphosa, Hardjo, Icterohaemorrhagiae, Pomona and Bratislava, with a cut-off value of ⩾1:100. Five purpose-bred cats were infested with wild-caught Ixodes scapularis adults with an average B burgdorferi infection rate of 50%, and tested for antibodies against B burgdorferi C6 peptide and DNA in skin biopsies, as well as by MAT. Sera from 66 azotemic and 75 non-azotemic cats ⩾10 years of age were tested for Leptospira species antibodies using the MAT and results were compared by the χ(2) test. RESULTS: Both SPF cats seroconverted by week 3 and formed antibodies against at least one serovar. There was no cross-reactivity in the MAT using samples from cats with antibodies to B burgdorferi. MAT results were positive for 4/66 azotemic cats and 8/75 non-azotemic cats; these results were not statistically different. CONCLUSIONS AND RELEVANCE: The MAT can be interpreted using feline serum and does not appear to cross-react in cats with B burgdorferi antibodies. There was no association between Leptospira species MAT results and azotemia in this group of aged client-owned cats but further studies are needed to determine if leptospirosis contributes to feline chronic kidney disease.

Prevention of immunodeficiency virus induced CD4+ T-cell depletion by prior infection with a non-pathogenic virus.

Immune dysregulation initiated by a profound loss of CD4+ T-cells is fundamental to HIV-induced pathogenesis. Infection of domestic cats with a non-pathogenic lentivirus prevalent in the puma (puma lentivirus, PLV or FIV(pco)) prevented peripheral blood CD4+ T-cell depletion caused by subsequent virulent FIV infection. Maintenance of this critical population was not associated with a significant decrease in FIV viremia, lending support to the hypothesis that direct viral cytopathic effect is not the primary cause of immunodeficiency. Although this approach was analogous to immunization with a modified live vaccine, correlates of immunity such as a serum-neutralizing antibody or virus-specific T-cell proliferative response were not found in protected animals. Differences in cytokine transcription profile, most notably in interferon gamma, were observed between the protected and unprotected groups. These data provide support for the importance of non-adaptive enhancement of the immune response in the prevention of CD4+ T-cell loss.