Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.

The aim of this study was to evaluate changes in coagulation tests, haptoglobin concentrations and leukocyte counts in rabbits with right-ventricle pacing medicated with acetylsalicylic acid (ASA). Blood was collected from 35 non-anaesthetised males from the jugular vein at baseline, one and two months after pacemaker implantation. Animals were divided into two groups: non-medicated and medicated with ASA. Total leukocyte and platelet counts were measured on an automatic veterinary flow cytometry haematological analyser. Prothrombin time, activated partial thromboplastin time, fibrinogen levels and D-dimers were determined from citrated blood. We found significantly elevated activated partial thromboplastin times and prothrombin times in ASA in comparison to the control group, but not within the ASA group over time. We also observed a decrease in platelet counts in the control group over time, but not in comparison to the ASA group. No significant changes in total leukocyte counts and haptoglobin concentrations were detected. Medication with ASA may alter coagulation profiles in rabbits with permanent transvenous pacing.

Right-ventricle pacing seems to have no influence on hemostasis in rabbits.

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