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In vitro effect of pimobendan on platelet aggregation in dogs

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  • 1 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
  • | 2 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
  • | 3 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
  • | 4 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
  • | 5 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.
  • | 6 Department of Veterinary Clinical Sciences and the Veterinary Teaching Hospital, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

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.

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.

Contributor Notes

Dr. Shipley's present address is Bay Area Veterinary Specialists, 12855 Gulf Frwy, Houston, TX 77034.

Dr. Fiakpui's present address is Strömsholm Small Animal Referral Hospital, Djursjukhusvägen 11, 734 94 Strömsholm, Sweden.

No funding was provided for this project.

The authors have no conflict of interest to report.

Presented in abstract form at the 29th Annual American College of Veterinary Internal Medicine Scientific Forum, Denver, June 2011.

The authors thank Dr. George E. Moore for statistical advice and analysis.

Address correspondence to Dr. Hogan (hogandf@purdue.edu).