ABSTRACT
Dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y12 receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y1 and P2Y12 ADP receptors, may be a novel and promising antiplatelet drug candidate. However, the salutary antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited in vivo recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes.
Subject(s)
Coronary Thrombosis/veterinary , Dinucleoside Phosphates/therapeutic use , Dog Diseases/drug therapy , Platelet Activation/drug effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Animals , Coronary Thrombosis/drug therapy , Coronary Thrombosis/metabolism , Dog Diseases/metabolism , Dogs , Female , Humans , Platelet Aggregation Inhibitors/therapeutic use , Receptors, Purinergic P2Y1/metabolism , Receptors, Purinergic P2Y12/metabolismSubject(s)
Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/veterinary , Cat Diseases/diagnostic imaging , Coronary Thrombosis/complications , Coronary Thrombosis/veterinary , Ventricular Outflow Obstruction/veterinary , Animals , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cats , Coronary Thrombosis/diagnostic imaging , Male , Ultrasonography , Ventricular Outflow Obstruction/complications , Ventricular Outflow Obstruction/diagnostic imagingABSTRACT
A dog was examined because of cardiac tamponade secondary to pericardial effusion. Masses adjacent to the right atrial and ventricular walls were revealed by echocardiography. Pericardectomy and biopsies of the masses established the diagnosis of idiopathic hemorrhagic pericardial effusion with organized thrombi. The dog was healthy 3 months after surgery. These organized thrombi mimicked cardiac neoplasia echocardiographically, and such a possibility should be included in the list of differential diagnoses of cardiac masses.
