Contribution of in vivo models of thrombosis to the discovery and development of novel antithrombotic agents

Leadley, Robert J.; Chi, Liguo; Rebello, Sam; Gagnon, Alison W.

doi:10.1016/s1056-8719(00)00095-2

Cited by 85 publications

(51 citation statements)

References 118 publications

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“…In this case, the choice of the animal model of thrombosis to evaluate the efficiency of antiplatelet, antithrombotic or thrombolytic drugs in preclinical studies is crucial. Numerous animal models of thrombosis-induced MI have been proposed in the last decades (Leadley et al, 2000). Another example was from porcine model of myocardial infarction induced by topical application of ferric chloride to the LAD coronary artery, which was validated to quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture (Dogne et al, 2005).…”

Section: Swine Models With Thrombosis Formation In Coronary Arterymentioning

confidence: 99%

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

Liu¹,

Li²

2012

Advances in Electrocardiograms - Clinical Applications

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Section: Swine Models With Thrombosis Formation In Coronary Arterymentioning

confidence: 99%

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

Liu¹,

Li²

2012

Advances in Electrocardiograms - Clinical Applications

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“…Several excellent reviews covering the different theoretical and technical aspects of thrombosis and thrombolysis models have been published previously (2,(11)(12)(13)(14)(15). These reviews, along with more specialized reviews of models of atherosclerosis (16), restenosis (17), and stroke (18) provide comprehensive information regarding the details of many models and provide the pathological rationale for using specific models for specific diseases.…”

Section: Selection Of Animal Modelmentioning

confidence: 99%

“…Despite these limitations, animal models predict the clinical effectiveness of drugs for the treatment and prevention of thrombotic diseases fairly well. A list of such drugs is presented in a recent review by Leadleey et al (2). The clinical usefulness of an antithrombotic drug is determined in part by safety/efficacy ratio with respect to bleeding risk.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Models for the Evaluation of Antithrombotics and Thrombolytics

Mousa

2010

Anticoagulants, Antiplatelets, and Thrombolytics

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The development and application of animal models of thrombosis have played a crucial role in the discovery and validation of novel drug targets and the selection of new agents for clinical evaluation, and have informed dosing and safety information for clinical trials. These models also provide valuable information about the mechanisms of action/interaction of new antithrombotic agents. Small and large animal models of thrombosis and their role in the discovery and development of novel agents are described. Methods and major issues regarding the use of animal models of thrombosis, such as positive controls, appropriate pharmacodynamic markers of activity, safety evaluation, species specificity, and pharmacokinetics, are highlighted. Finally, the use of genetic models of thrombosis/hemostasis and how these models have aided in the development of therapies that are presently being evaluated clinically are presented.

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“…Large animal models were the first to be used as they provide large vessels more similar to humans than rodents 1 . However, high cost, the larger facilities required and the difficulty in manipulating them genetically are major drawbacks to their use and large animals are now limited to late preclinical studies once preliminary tests on rodents have given conclusive results 2 .…”

Section: Introductionmentioning

confidence: 99%

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

Bonnard

Hagemeyer

2015

JoVE

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Severe thrombosis and its ischemic consequences such as myocardial infarction, pulmonary embolism and stroke are major worldwide health issues. The ferric chloride injury is now a well-established technique to rapidly and accurately induce the formation of thrombi in exposed veins or artery of small and large diameter. This model has played a key role in the study of the pathophysiology of thrombosis, in the discovery and validation of novel antithrombotic drugs and in the understanding of the mechanism of action of these new agents. Here, the implementation of this technique on a mesenteric vessel and carotid artery in mice is presented. The method describes how to label circulating leukocytes and platelets with a fluorescent dye and to observe, by intravital microscopy on the exposed mesentery, their accumulation at the injured vessel wall which leads to the formation of a thrombus. On the carotid artery, the occlusion caused by the clot formation is measured by monitoring the blood flow with a Doppler probe. Video LinkThe video component of this article can be found at

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Contribution of in vivo models of thrombosis to the discovery and development of novel antithrombotic agents

Cited by 85 publications

References 118 publications

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

Novel Porcine Models of Myocardial Ischemia/Infarction – Technical Progress, Modified Electrocardiograms Validating, and Future Application

In Vivo Models for the Evaluation of Antithrombotics and Thrombolytics

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

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