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

Maithili Sashindranath, Sharelle Sturgeon, Shauna Louise French, Daphne D. D. Craenmehr, Carly Selan, Susanna Freddi, Chad Johnson, Stephen Cody, Warwick Nesbitt, Justin Hamilton, Stephen H. Cody, Warwick Nesbitt, Justin Hamilton, Harshal Nandurkar

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalThrombosis and Haemostasis
Volume3
Issue number2
DOIs
Publication statusPublished - Apr 2019

Cite this

Sashindranath, Maithili ; Sturgeon, Sharelle ; French, Shauna Louise ; Craenmehr, Daphne D. D. ; Selan, Carly ; Freddi, Susanna ; Johnson, Chad ; Cody, Stephen ; Nesbitt, Warwick ; Hamilton, Justin ; Cody, Stephen H. ; Nesbitt, Warwick ; Hamilton, Justin ; Nandurkar, Harshal. / The mode of anesthesia influences outcome in mouse models of arterial thrombosis. In: Thrombosis and Haemostasis. 2019 ; Vol. 3, No. 2. pp. 197-206.
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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.",
author = "Maithili Sashindranath and Sharelle Sturgeon and French, {Shauna Louise} and Craenmehr, {Daphne D. D.} and Carly Selan and Susanna Freddi and Chad Johnson and Stephen Cody and Warwick Nesbitt and Justin Hamilton and Cody, {Stephen H.} and Warwick Nesbitt and Justin Hamilton and Harshal Nandurkar",
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The mode of anesthesia influences outcome in mouse models of arterial thrombosis. / Sashindranath, Maithili; Sturgeon, Sharelle; French, Shauna Louise; Craenmehr, Daphne D. D.; Selan, Carly; Freddi, Susanna; Johnson, Chad; Cody, Stephen; Nesbitt, Warwick; Hamilton, Justin; Cody, Stephen H.; Nesbitt, Warwick; Hamilton, Justin; Nandurkar, Harshal.

In: Thrombosis and Haemostasis, Vol. 3, No. 2, 04.2019, p. 197-206.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The mode of anesthesia influences outcome in mouse models of arterial thrombosis

AU - Sashindranath, Maithili

AU - Sturgeon, Sharelle

AU - French, Shauna Louise

AU - Craenmehr, Daphne D. D.

AU - Selan, Carly

AU - Freddi, Susanna

AU - Johnson, Chad

AU - Cody, Stephen

AU - Nesbitt, Warwick

AU - Hamilton, Justin

AU - Cody, Stephen H.

AU - Nesbitt, Warwick

AU - Hamilton, Justin

AU - Nandurkar, Harshal

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

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DO - 10.1002/rth2.12184

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JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

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ER -