Pharmacokinetics and pharmacodynamics of a therapeutic dose of unfractionated heparin (200 U/kg) administered subcutaneously or intravenously to healthy dogs.

BACKGROUND: Heparin treatment has been recommended for dogs in hypercoagulable states such as disseminated intravascular coagulation, however, potential benefits have to be balanced against the bleeding risk if overdosage occurs. A better understanding of the pharmacology of heparin and tests to monitor heparin therapy in dogs may help prevent therapeutic hazards. OBJECTIVES: The purpose of this study was to evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after intravenous (IV) and subcutaneous (SC) administration and to compare these effects with plasma heparin concentrations assessed by its antifactor Xa (aXa) activity. METHODS: 200 U/kg of UFH were administered IV and SC to 5 healthy adult Beagle dogs with a washout period of at least 3 days. Activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma aXa activity were determined in serial blood samples. RESULTS: After IV injection, PT remained unchanged except for a slight increase in 1 dog; APTT was not measurable (>60 seconds) for 45-90 minutes, and then decreased gradually to baseline values between 150 and 240 minutes. High plasma heparin concentrations were observed (maximal concentration = 4.64 +/-1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semilogarithmic curve, but returned to baseline slightly more slowly (t240-t300 minutes) than did APTT. After SC administration, APTT was moderately prolonged (by a ratio of 1.55 +/-0.28 APTT t0, range 1.35-2.01) between 1 and 4 hours after administration. Plasma aXa activity reached a maximum of 0.56 +/-0.20 aXa U/mL (range 0.42-0.9 U/mL) after 132 +/-26.8 minutes; this lasted for 102 +/-26.8 minutes. Prolongation of APTTs of 120-160% corresponded to plasma heparin concentrations of 0.3-0.7 aXa U/mL. CONCLUSIONS: As in humans, the pharmacokinetics of UFH in dogs was nonlinear. Administration of 200 U/kg of UFH SC in healthy dogs resulted in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. These findings need to be confirmed in diseased animals.

Comparison of early and late feline immunodeficiency virus encephalopathies.

DESIGN: The study of the early and late stages of encephalopathy following infection by the feline immunodeficiency virus (FIV) was carried out with laboratory and naturally infected cats. INTERVENTIONS: Animals infected experimentally were injected with three different isolates of the virus, administered either intracerebrally or intravenously, and sacrificed at 7 days, 1 and 6 months (intracerebral injection), and 2, 6 and 12 months (intravenous injection) post-inoculation, respectively. CONCLUSIONS: General features of encephalopathy were found to be identical, regardless of the method of inoculation or the viral strain used. Moderate gliosis and glial nodules, sometimes associated with perivascular infiltrates and white matter pallor, were observed at 1 month (intracerebral injection) and 2 months (intravenous injection), and remained unchanged until 12 months post-inoculation. The fact that these initial stages are identical for intravenously and intracerebrally inoculated cats suggests that the virus enters the brain very quickly in intravenously infected animals. Encephalopathy in cats naturally infected with FIV only consisted of gliosis, glial nodules, white matter pallor, meningeal perivascular calcification and meningitis. These lesions were more frequent and more severe in the group coinfected with feline leukaemia virus and feline infectious peritonitis virus. Although multinucleated cells were rare, the strong similarities between HIV and simian immunodeficiency virus encephalopathies at comparable stages support the view that FIV infection may represent an interesting model for a physiopathological approach of HIV infection of the central nervous system.

[The effect of a single dose of dexamethasone on the production of superoxide anion and on the chemotaxis of blood polynuclear neutrophils in the horse]. / Effets d'une dose unique de dexamethasone sur la production d'anion superoxyde et sur le chimiotactisme des polynucleaires neutrophiles sanguins du cheval.

Chemotaxis and superoxide anion production of neutrophils in healthy horses were investigated before and 8 h after, a single injection of dexamethasone at a dose of 0.045 mg/kg. Chemotaxis was studied by the technique of migration under agarose and superoxyde production was measured by ferricytochrome c reduction. Superoxide anion production was not changed, but the chemotactic index, with zymosan activated horse serum, was increased. The FMLP chemoattractant effect, at 10(-4) M, was slightly enhanced.

In vivo and in vitro effects of three glucocorticoids on blood leukocyte chemotaxis in the dog.

The effects of three glucocorticoids on random migration (RM) and oriented migration (OM) of dog blood leukocytes either from dogs treated in vivo (at therapeutic dosage regimen) or leukocytes treated in vitro (at pharmacological concentrations), were investigated using an agarose gel technique. After in vivo treatment, methylprednisolone sodium succinate (MPSS) produced a stimulation of both RM and OM in the three treated dogs. Dexamethasone produced a stimulation of both RM and OM in the three treated dogs. Dexamethasone produced a stimulation of these parameters in all but one of the three treated dogs, but the difference was not statistically significant. After in vitro treatment of leukocytes from eight dogs, MPSS significantly stimulated OM. Dexamethasone was without significant effect except at a higher than therapeutic concentration (0.5 micrograms/ml), for which RM was stimulated. Hydrocortisone sodium succinate was without statistically significant effect. Under no conditions, except after suprapharmacological concentrations, did glucocorticoids inhibit RM or OM.

Plasma fibrinogen measurement in the horse: comparison of Millar's technique with a chronometric technique and the QBC-Vet Autoreader.

Plasma fibrinogen is widely used in horse practice as an unspecific positive marker of inflammatory diseases; it is also lowered in disseminated intravascular coagulation. Three fibrinogen measurement methods--Millar's heat-denaturation in a microhaematocrit tube, automated reader for heat-denaturation, and chronometric measurement of clot formation after addition of excess thrombin-were compared by means of Passing-Bablock's regression and Bland-Altman difference plots, in blood plasma of 30 clinically healthy and 57 diseased horses. Correlations between the three techniques were excellent (r >0.92). The two heat-denaturation techniques correlated very closely up to 6 g l(-1), above which the results obtained by Millar's technique started to fall below those obtained by the automatic reader. There was proportional bias between Millar's technique and the chronometric technique, with the latter producing results some 30% lower, indicating that reference intervals and decision limits should be adapted accordingly.

Value of so called cholestasis markers in the dog: an experimental study.

In experimental bile obstruction in dogs, the most sensitive change in blood plasma composition is the increase in alkaline phosphatase activity which occurs after eight hours. Maximum alkaline phosphatase activities (approximately 100 times normal values) occur between the fifth and the 14th day. The increase in activity is accompanied by smaller increases in gamma-glutamyl transferase activity, and total bilirubin concentration also increases to a smaller extent and less regularly. Cholestasis also induces an intense cytolysis which is demonstrated mainly by increases in glutamate dehydrogenase and alanine amino transferase activities which are more intense and lasting than those induced by 0.5 ml/kg carbon tetrachloride.

Comparison of four methods for determination of total protein concentrations in pleural and peritoneal fluid from dogs.

OBJECTIVE: To compare 4 techniques for determination of total protein concentrations in peritoneal and pleural effusions from dogs. SAMPLE POPULATION: 23 peritoneal and 12 pleural fluid samples from 35 dogs with various abnormalities. PROCEDURE: Samples were collected into tubes containing EDTA, centrifuged, and stored at -20 C until total protein concentrations were assessed. Protein concentration in each sample was determined by use of urine test strips, refractometry, and Bradford and biuret techniques. Accuracy of each method was determined, using dilutions of human control sera. RESULTS: There was good correlation among results of all quantitative procedures. Results of the biuret technique were more accurate than results of the Bradford assay. Refractometry underestimated protein concentration in samples with < 20 g of protein/L. Results of urine test strips correctly classified effusion samples into 2 groups on the basis of total protein concentrations less than or greater than 20 g/L. CONCLUSIONS AND CLINICAL RELEVANCE: Results of any of these 4 techniques can be used to rapidly and efficiently differentiate peritoneal and pleural fluid from dogs into transudates and exudates on the basis of total protein concentration less than or greater than 20 g/L, respectively.

Ingestion of low doses of deoxynivalenol does not affect hematological, biochemical, or immune responses of piglets.

Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is a frequent contaminant of cereals. Because of their rich cereal diet, pigs could be exposed to this mycotoxin. Pigs are among the animal species showing the greatest sensitivity to DON. Effects of intermediate to high levels of DON on pigs are well known and include feed refusal, decreased feed intake, and alteration of the immune response. Effects of low levels of DON, which are commonly detected in contaminated feed, remain unknown. The aim of this study was to investigate the effect of a diet naturally contaminated with a low concentration of DON (0, 280, 560, or 840 microg/kg of feed) on performance of weanling piglets and on 34 hematological, biochemical, and immune variables. Low doses of DON did not alter the animal performances (feed intake and BW gain). Such low levels of DON did not modify the 9 hematological variables measured (including white blood cell, red blood cell, and platelet counts, relative numbers of neutrophils and lymphocytes, and hematocrit and hemoglobin concentrations) or the 18 biochemical variables tested (including cations, glucose, urea, creatinine, bilirubin, cholesterol and triglyceride concentrations, and plasma enzyme activity). Similarly, no effect of low doses of DON was observed on the immune responses of the animals (immunoglobulin subset concentration, lymphocyte proliferation, and cytokine production).

Adverse haematological effects of vinblastine, prednisolone and cimetidine treatment: a retrospective study in fourteen dogs with mast cell tumours.

Vinblastine toxicity is poorly documented in dogs. The aim of this study was to investigate the haematological alterations in dogs treated with vinblastine and prednisolone. Fourteen dogs with mast cell tumours (MCT) were selected on at least one of the following criteria: lymph node infiltration, surgical margin infiltration, grade II MCTs with Ki-67 >10%, and grade III MCTs. Starting 15 days after surgery, the dogs were given vinblastine (2 mg/m2 i.v. four times weekly, then twice monthly for 2 months) and prednisolone (2 mg/kg/day p.o.). An EDTA blood sample was collected weekly for complete blood count (CBC). A total of 98 doses of vinblastine were given to the 14 dogs and 114 CBC were performed. Abnormal haematological findings were observed in 12 CBCs from five dogs, which represent a prevalence of 20% of the total CBCs performed in these animals. The most prevalent abnormal finding was thrombopenia (9/12) most often with grade I toxicity (6/9). In conclusion, the risk of occurrence of adverse haematological effects resulting from vinblastine-prednisolone treatment seems limited in dogs with MCT and it should not be overestimated.

Hematological parameters and visceral lesions relationships in rabbit viral hemorrhagic disease.

Twenty rabbits were inoculated with a suspension of Viral Hemorrhagic Disease virus. Hemostatic functions were assessed every sixth hour from 6 to 60 hours post-inoculation. Tissue samples obtained at the same intervals allowed the study of the development of lesions throughout the experiment. Biological signs of Disseminated Intravascular Coagulation (DIC) were detected on and after 30 h post-inoculation and consisted of prolonged One Stage Prothrombin Time and Activated Partial Thrombin Time, the decrease of factors V, VII, and X and high levels of soluble fibrin monomer complexes and D-dimers. A reduction of thrombocyte numbers, heterophils and lymphocytes was associated. The close association of DIC and necrotizing hepatitis lesions suggested the hepatic lesions to be the most important DIC triggering factor. Other mechanisms are discussed.

Characterization of alkaline phosphatase in polymorphonuclear neutrophils from normal sheep.

This paper is an attempt to the analysis of the main biochemical characteristics of alkaline phosphatase from sheep polymorphonuclear neutrophils. Ten male adult Romanoff X Berrichon sheep were studied. Alkaline phosphatase was analyzed from cell homogenates, after extraction and solubilization steps. The Vmax and Km values for 4-nitrophenylphosphate at pH = 9.80 were 347.3 +/- 34 IU/ml and 0.7 +/- 0.18 mmol/l, respectively. The pH optimum was 9.80 with 4-nitrophenylphosphate. L-Homoarginine and EDTA, but not L-phenylalanine, inhibited the enzyme. Magnesium above a concentration of 0.5 mmol/l has shown a protective effect against inhibition by 115, 156 and 250 mmol/l urea (final concentration). Sheep neutrophil alkaline phosphatase was found to be very heat-labile. Polyacrylamide gel electrophoresis indicated a single band of activity with a relative mobility similar to that of the slow component of bone and liver isozymes. It is suggested from the above results that sheep neutrophil alkaline phosphatase shares several biochemical properties similar to those of hepatic bone tissue isozyme.