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  • Author or Editor: Henry W. Green x
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Abstract

Objective—To determine whether ticlopidine exerts an antiplatelet effect, estimate the pharmacodynamics of ticlopidine, and evaluate any acute adverse effects associated with administration of ticlopidine in cats.

Animals—8 domestic purpose-bred sexually intact male cats.

Procedure—Ticlopidine was administered orally (50 mg, q 24 h; 100 mg, q 24 h; 200 mg, q 24 h; and 250 mg, q 12 h). Each treatment period consisted of 10 days of drug administration. Platelet aggregation studies with adenosine diphosphate (ADP) and collagen and evaluation of oral mucosal bleeding times (OMBTs) were performed on days 3, 7, and 10 during each drug administration. Serotonin was measured to evaluate secretion at baseline and on day 10 for cats that received the 250-mg dosage.

Results—A significant reduction in platelet aggregation was detected in response to ADP on days 7 and 10 at 100 mg, on day 3 at 200 mg, and on days 3, 7, and 10 at 250 mg. A significant increase in the OMBT and decrease in serotonin release on day 10 at 250 mg was also detected; however, the cats had anorexia and vomiting at the 250-mg dosage.

Conclusions and Clinical Relevance—Although there was a consistent antiplatelet effect at the 250-mg dosage, there was dose-dependent anorexia and vomiting that we conclude precludes the clinical usefulness of this drug in cats. ( Am J Vet Res 2004;65:327–332)

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To establish practical doses and administration frequencies of fondaparinux for cats that would approximate human therapeutic peak and trough plasma anti–factor Xa activities for thromboprophylaxis (TP) and thrombosis treatment (TT) protocols.

Animals—6 healthy adult purpose-bred cats.

Procedures—Dosage protocols for TP and TT were selected on the basis of a single compartment pharmacokinetic model incorporating data from humans but modified to account for the higher body weight–normalized cardiac output of cats. Fondaparinux was administered at 0.06 mg/kg, SC, every 12 hours (TP) for 7 days in one session, and 0.20 mg/kg, SC, every 12 hours (TT) for 7 days in another, with a minimum of 1 week separating the sessions. Plasma anti–factor Xa activity was measured before fondaparinux administration (day 1) and at 2 (peak) and 12 (trough) hours after drug administration on days 1 and 7. Platelet aggregation and thromobelastographic (TEG) parameters were also measured 2 hours after drug administration on day 7.

Results—Peak plasma anti–factor Xa activities on day 7 for TP (median, 0.59 mg/L; range, 0.36 to 0.77 mg/L) and TT (median, 1.66 mg/L; range, 1.52 to 2.00 mg/L) protocols were within therapeutic ranges for humans. However, only the TP protocol achieved trough anti–factor Xa activity considered therapeutic in humans (median, 0.19 mg/L; range, 0.00 to 0.37 mg/L) on day 7. There were significant changes in the TEG parameters at peak for the TT protocol, suggesting a hypocoagulable state. No significant changes in platelet aggregation were evident for either protocol.

Conclusions and Clinical Relevance—A fondaparinux dosage of 0.06 or 0.20 mg/kg, SC, every 12 hours, was sufficient to achieve a peak plasma anti–factor Xa activity in cats that has been deemed therapeutic in humans. This study provided preliminary data necessary to perform fondaparinux dose-determination and clinical efficacy studies.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether pimobendan has in vitro antithrombotic properties through inhibition of platelets in canine blood samples.

Animals—10 healthy adult dogs.

Procedures—Blood samples were collected from each dog into tubes containing hirudin or sodium citrate. Pimobendan was added to blood samples (final concentration, 0.0, 0.01, 0.1, 1.0, or 10.0μM) containing hirudin prior to undergoing collagen- and ADP-induced whole blood impedance aggregometry. Plasma thromboxane concentrations were measured after platelet aggregation. Pimobendan was also added to blood samples (0.0, 0.01, or 10.0μM) containing sodium citrate prior to thromboelastographic evaluation.

Results—Compared with findings for 0.0μM pimobendan, composite platelet aggregation (area under the curve [AUC]) and maximal platelet aggregation (aggregation units [AUs]) at 10.0μM pimobendan were significantly decreased for collagen-induced aggregation (AUC, 349.7 ± 58.4 vs 285.1 ± 72.2; maximal platelet aggregation, 196.2 ± 25.8 AUs vs 161.5 ± 38.0 AUs), and the AUC and velocity of aggregation at 10.0μM pimobendan were significantly decreased for ADP-induced aggregation (AUC, 268.5 ± 35.1 vs 213.4 ± 77.2; velocity of aggregation, 15.7 ± 2.9 AUs/min vs 11.8 ± 3.5 AUs/min). Pimobendan had no significant effect on plasma thromboxane concentration or thromboelastographic variables, regardless of concentration.

Conclusions and Clinical Relevance—In vitro, pimobendan had an antiplatelet effect in canine blood samples at a concentration 1,000-fold higher than that clinically achievable. These antiplatelet properties do not appear to contribute to the positive clinical profile of the drug in dogs. Pimobendan administration would not appear to confer a risk for bleeding and does not have to be avoided in dogs with thrombocytopenia or those concurrently receiving antiplatelet drugs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To estimate the left atrium–to–aorta ratio (LA:Ao) and establish 95% prediction intervals for left ventricular M-mode transthoracic echocardiographic measurements in clinically normal adult Dachshunds.

ANIMALS 40 healthy Dachshunds.

PROCEDURES For each dog, 3 standard 2-D echocardiographic methods (diameter, circumference, and cross-sectional area) were used to measure the left atrium and aorta and calculate the LA:Ao from right parasternal short axis (RPSA) images obtained at the level of the aortic valve cusps. Left ventricular M-mode measurements were acquired from RPSA images obtained at the chordal level immediately below the mitral valve. Descriptive data were generated, and the 95% prediction intervals were calculated by use of an allometric scaling equation and linear regression and compared with those calculated on the basis of data obtained from dogs of multiple breeds in a previous study.

RESULTS The mean (SD) LA:Ao was 1.40 (0.13), 2.09 (0.17), and 2.85 (0.48) for the diameter, circumference, and cross-sectional area methods, respectively. The 95% prediction intervals for the left ventricular M-mode measurements determined by an allometric scaling equation on the basis of Dachshund-specific data were narrower than those determined on the basis of data obtained from dogs of multiple breeds. For that allometric equation, scaling exponents on the basis of Dachshund-specific data ranged from 0.129 to 0.397 and did not absolutely conform to the presumed index for linear measurements (ie, body weight0.333).

CONCLUSIONS AND CLINICAL RELEVANCE The LA:Aos and 95% prediction intervals calculated in this study can be used as preliminary guidelines for echocardiographic measurements of clinically normal Dachshunds.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate antiplatelet effects and pharmacodynamics of clopidogrel in cats.

Design—Original study.

Animals—5 purpose-bred domestic cats.

Procedure—Clopidogrel was administered at dosages of 75 mg, PO, every 24 hours for 10 days; 37.5 mg, PO, every 24 hours for 10 days; and 18.75 mg, PO, every 24 hours for 7 days. In all cats, treatments were administered in this order, with at least 2 weeks between treatments. Platelet aggregation in response to ADP and collagen and oral mucosal bleeding times (OMBTs) were measured before and 3, 7, and 10 days (75 and 37.5 mg) or 7 days (18.75 mg) after initiation of drug administration. Serotonin concentration in plasma following stimulation of platelets with ADP or collagen was measured before and on the last day of drug administration. Platelet aggregation, OMBT, and serotonin concentration were evaluated at various times after drug administration was discontinued to determine when drug effects were lost.

Results—For all 3 dosages, platelet aggregation in response to ADP, platelet aggregation in response to collagen, and serotonin concentration were significantly reduced and OMBT was significantly increased at all measurement times during drug administration periods. All values returned to baseline values by 7 days after drug administration was discontinued. No significant differences were identified between doses. None of the cats developed adverse effects associated with drug administration.

Conclusions and Clinical Relevance—Results suggest that administration of clopidogrel at dosages ranging from 18.75 to 75 mg, PO, every 24 hours, results in significant antiplatelet effects in cats. (J Am Vet Med Assoc 2004;225:1406–1411)

Restricted access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare distributions of survivin among tissues from urinary bladders of dogs with cystitis, transitional cell carcinoma (TCC), or histologically normal urinary bladders.

Sample Population—24 archived and 7 fresh-frozen specimens of urinary bladders from dogs with cystitis.

Procedures—Immunohistochemical analysis of archived tissue specimens was performed to identify survivin protein in the nucleus and cytoplasm of cells by use of polyclonal rabbit anti-survivin antibody. Tissues that contained ≥ 5% immunoreactive cells were considered positive for survivin protein. Reverse-transcription PCR analysis was performed on fresh-frozen tissues to identify survivin mRNA. Data on tissues from dogs with TCC or histologically normal urinary bladders that were obtained during another study were used for statistical comparisons.

Results—Twelve of 24 (50%) cystitic tissues were positive for nuclear survivin, compared with 28 of 41 (68%) TCC tissues and 0 of 46 (0%) normal tissues. Two of 24 (8%) cystitic tissues were positive for cytoplasmic survivin, compared with 7 of 41 (17%) TCC tissues and 17 of 46 (37%) normal tissues. Proportions of specimens that contained nuclear or cytoplasmic survivin were significantly different between cystitic and normal tissues but not between cystitic and TCC tissues. Four of 7 cystitic tissues were positive for survivin mRNA, which was comparable with results for TCC and normal tissues.

Conclusions and Clinical Relevance—Nuclear survivin was detected in TCC and cystitic tissues but not in normal urinary bladder tissues. Additional studies are needed to determine whether nuclear survivin contributes to the development or progression of TCC.

Full access
in American Journal of Veterinary Research