Dataset Information

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

ABSTRACT:

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 FeCl₃ 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 FeCl₃ injury was assessed. The efficacy of Eptifibatide was studied in each cohort and clot composition following FeCl₃ 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 FeCl₃ and electrolytic models, injury severity had to be increased in mice under ket-x anesthesia to achieve rapid occlusion. FeCl₃-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 FeCl₃ 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.

SUBMITTER: Sashindranath M

PROVIDER: S-EPMC6462741 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Sashindranath Maithili M Sturgeon Sharelle A SA French Shauna S Craenmehr Daphne D D DDD Selan Carly C Freddi Susanna S Johnson Chad C Cody Stephen H SH Nesbitt Warwick S WS Hamilton Justin R JR Nandurkar Harshal H HH

Research and practice in thrombosis and haemostasis 20190215 2

<h4>Background</h4>Arterial thrombosis models are important for preclinical evaluation of antithrombotics but how anesthetic protocol can influence experimental results is not studied.<h4>Objectives</h4>We studied how three most commonly used rodent anesthetics affect the induction of thrombosis and thrombus resolution with antiplatelet agent integrilin (Eptifibatide).<h4>Methods</h4>The Folts, electrolytic, and FeCl<sub>3</sub> models of carotid artery thrombosis were evaluated. The extent of b ...[more]

PMID: 31011704

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Project description:BACKGROUND:Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE:To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN:Prospective autopsy study. SETTING:Single pathology department. PARTICIPANTS:11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS:Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS:Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION:The sample was small. CONCLUSION:COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE:None.

Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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