In Vivo Models of Thrombosis

Chi, Liguo; Rebello, Sam; Lucchesi, Benedict R.

doi:10.1007/978-3-642-59942-2_4

Cited by 8 publications

(3 citation statements)

References 96 publications

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“…Carotid artery injury models have regular variations in severity, clot composition, and clot size and it is widely accepted that the results of a particular anti-thrombotic drug being developed are model dependent. 17 But here we show that the choice of anesthesia also needs to be carefully considered when testing new compounds for treatment of atherothrombosis.…”

Section: Discussionmentioning

confidence: 90%

The mode of anesthesia influences outcome in mouse models of arterial thrombosis

Sashindranath

Sturgeon

French

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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Background Arterial thrombosis models are important for preclinical evaluation of antithrombotics but how anesthetic protocol can influence experimental results is not studied. Objectives We studied how three most commonly used rodent anesthetics affect the induction of thrombosis and thrombus resolution with antiplatelet agent integrilin (Eptifibatide). Methods The Folts, electrolytic, and FeCl 3 models of carotid artery thrombosis were evaluated. The extent of blood flow reduction required to elicit cyclic flow reductions ( CFR ) was examined in the Folts model. The occlusion time and stability following electrolytic or FeCl 3 injury was assessed. The efficacy of Eptifibatide was studied in each cohort and clot composition following FeCl 3 application was assessed histologically. Results Isoflurane and ketamine‐xylazine (ket‐x) elicited higher basal blood flow velocities. For reliable CFR in the Folts model, a higher degree of blood flow reduction was required under ket‐x and isoflurane. For the FeCl 3 and electrolytic models, injury severity had to be increased in mice under ket‐x anesthesia to achieve rapid occlusion. FeCl 3 ‐injured artery sections from ket‐x and isoflurane‐treated mice showed vessel dilatation and clots that were more fibrin/red‐cell rich compared to pentobarbitone. Integrilin led to cycle abolishment for all three Folts‐injury cohorts but for the electrolytic model a 2.5‐fold higher dose was required to restore blood flow under pentobarbitone. Integrilin after FeCl 3 arterial injury was partially ineffective in isoflurane‐treated mice. Conclusions Anesthesia impacts rodent carotid artery occlusion experiments and alters integrilin efficacy. It is important to consider anesthetic protocols in animal experiments involving pharmacological agents for treatment of atherothrombosis.

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Section: Discussionmentioning

confidence: 90%

The mode of anesthesia influences outcome in mouse models of arterial thrombosis

Sashindranath

Sturgeon

French

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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“…In our patient, potential underlying myocardial ischemia caused subendothelial injury with inflammatory changes, and left ventricle regional wall akinesia resulted in blood stasis. This combination contributed to the in vivo thrombus formation [9]. …”

Section: Discussionmentioning

confidence: 99%

Giant Left Ventricular Thrombus in a Patient with Acute Ischemic Stroke: A Case Report and Minireview

Fan

Silverstein

Khuddus

et al. 2018

Case Reports in Cardiology

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A 56-year-old healthy male with no obvious risk factors or significant past medical history was admitted to the emergency room with acute ischemic stroke. On his transthoracic echocardiography (TTE), an extremely large thrombus was detected at the apex involving the distal anterior wall. The thrombus was predominantly adherent but with a mobile tip. The patient was subsequently managed with dual antiplatelet therapy. In this report, we present an interesting case of an acute ischemic stroke secondary to a giant left ventricular thrombus in a patient with no past significant cardiac or neurologic medical history.

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“…This might be due to the high pressure and shear rate inside the shunts, causing thrombi to be more arterial in character (14). Compared to the arterial system, the development of thrombosis models in venous blood vessels tends to be more difficult in terms of reproducibility and variability (14). Complete stasis together with a thrombogenic stimulus (Wessler-type) has been used by a number of investigators to evaluate the effects of test compounds on venous thrombosis.…”

Section: Critical Assessment Of the Methodsmentioning

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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In Vivo Models of Thrombosis

Cited by 8 publications

References 96 publications

The mode of anesthesia influences outcome in mouse models of arterial thrombosis

The mode of anesthesia influences outcome in mouse models of arterial thrombosis

Giant Left Ventricular Thrombus in a Patient with Acute Ischemic Stroke: A Case Report and Minireview

In Vivo Models for the Evaluation of Antithrombotics and Thrombolytics

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