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High Shear Conditions Takes Place at the Edge of the Wound after Human and Mouse Vessel Injury

A. Yakusheva1,2,3, K. Butov2,3,4, F. Ataullakhanov2,3,5, C. Gachet1, M. Panteleev2,3,5, P. Mangin1

1Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S 1255, FMTS, Strasbourg, France, 2Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russian Federation, 3Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation, 4Histology Department, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation, 5Faculty of Physics, Moscow State University, Moscow, Russian Federation

Abstract Number: PB0030

Meeting: ISTH 2021 Congress

Theme: Coagulation and Natural Anticoagulants » Animal Models in Thrombosis and Hemostasis

Background: The importance of blood flow in regulating hemostasis is well known. The current view is that low flow (100 s-1 up to 2,000 s-1) occurs in healthy vessels, while high shear (> 2,000 s-1) is relevant to arterial thrombosis, notably around stenosed vessels. Targeting high shear has been proposed as an innovative strategy to selectively block thrombosis with a minor impact on hemostasis. However, the rheology occurring after vessel wall injury has never been measured experimentally.

Aims: To evaluate the shear rates at the edges of different wounds in mice and humans.

Methods: Intravital and electron microscopy was used to image thrombus formation in several novel models of hemostasis following needle-induced puncture or scissors-induced disruption of various vessels. Two laser doppler probes on both sides of the injury measured blood flow in the vessels throughout the hemostatic process, and ComSol software allowed to recalculate shear rates in the wound. In human the shear rate was calculated by applying Poiseuille’s equation with volumetric rates of blood loss after catheter placement.

Results:

Vessel Species Type of vessel injury Diameter of the injury, μm Shear rate at the wound, s-1 Shear rate in the intact vessel, s-1
Median 25-75% percentile
Carotid artery mouse puncture 125-140 11,600 6,700-30,400 950
Aorta mouse puncture 40-300 29,000 4,700-680,000 900
Femoral vein mouse puncture 80-165 22,200 7,100-50,000 1,000
Vena cava mouse puncture 70-280 40,500 24,100-2,7*106 200
Spermatic artery mouse disruption 215 2,500 1,800-3,300 900
Median cubital vein human puncture 310 7,400 5,400-27,300 250
410 3,500 2,300-5,400 250

The shear rates calculated for different scenarios
The shear rate at the edge of the wound induced with a needle was 80-, 10-, 33- and 100-times higher in mouse artery, aorta, vein and vena cava than the values in the same uninjured vessels (Table1). In the scissors-disruption model of the spermatic artery, a 3-fold increase at the lesion site was obtained when compared to homeostatic conditions. In humans, the shear rate upon the wound of cubital vein was 14,500 ± 5,000 s-1 and 3,700 ± 800 s-1 for 310 and 410 um of injury diameter (Table1), indicating that the shear reaches high levels following vessel damage.

Conclusions: Our results indicate that various types of injuries in small and large mouse and human vessels result in high shear rates. Elevated shear rate is not specific to arterial thrombosis, but also relevant to hemostasis.

To cite this abstract in AMA style:

Yakusheva A, Butov K, Ataullakhanov F, Gachet C, Panteleev M, Mangin P. High Shear Conditions Takes Place at the Edge of the Wound after Human and Mouse Vessel Injury [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/high-shear-conditions-takes-place-at-the-edge-of-the-wound-after-human-and-mouse-vessel-injury/. Accessed May 16, 2022.

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