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  • Author or Editor: Henry W. Green III x
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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.

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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