Dataset Information

Simulation of intrathrombus fluid and solute transport using in vivo clot structures with single platelet resolution.

ABSTRACT: The mouse laser injury thrombosis model provides up to 0.22 ?m-resolved voxel information about the pore architecture of the dense inner core and loose outer shell regions of an in vivo arterial thrombus. Computational studies were conducted on this 3D structure to quantify transport within and around the clot: Lattice Boltzmann method defined vessel hemodynamics, while passive Lagrangian Scalar Tracking with Brownian motion contribution simulated diffusive-convective transport of various inert solutes (released from lumen or the injured wall). For an input average lumen blood velocity of 0.478 cm/s (measured by Doppler velocimetry), a 0.2 mm/s mean flow rate was obtained within the thrombus structure, most of which occurred in the 100-fold more permeable outer shell region (calculated permeability of the inner core was 10(-11) cm(2)). Average wall shear stresses were 80-100 dyne/cm(2) (peak values >200 dyne/cm(2)) on the outer rough surface of the thrombus. Within the thrombus, small molecule tracers (0.1 kDa) experienced ~70,000 collisions/s and penetrated/exited it in about 1 s, whereas proteins (~50 kDa) had ~9000 collisions/s and required about 10 s (tortuosity ~2-2.5). These simulations help define physical processes during thrombosis and constraints for drug delivery to the thrombus.

SUBMITTER: Voronov RS

PROVIDER: S-EPMC3640668 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Simulation of intrathrombus fluid and solute transport using in vivo clot structures with single platelet resolution.

Voronov Roman S RS Stalker Timothy J TJ Brass Lawrence F LF Diamond Scott L SL

Annals of biomedical engineering 20130220 6

The mouse laser injury thrombosis model provides up to 0.22 μm-resolved voxel information about the pore architecture of the dense inner core and loose outer shell regions of an in vivo arterial thrombus. Computational studies were conducted on this 3D structure to quantify transport within and around the clot: Lattice Boltzmann method defined vessel hemodynamics, while passive Lagrangian Scalar Tracking with Brownian motion contribution simulated diffusive-convective transport of various inert ...[more]

PMID: 23423707

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Project description:The formation of wall-adherent platelet aggregates is a critical process in arterial thrombosis. A growing aggregate experiences frictional drag forces exerted on it by fluid moving over or through the aggregate. The magnitude of these forces is strongly influenced by the permeability of the developing aggregate; the permeability depends on the aggregate's porosity. Aggregation is mediated by formation of ensembles of molecular bonds; each bond involves a plasma protein bridging the gap between specific receptors on the surfaces of two different platelets. The ability of the bonds existing at any time to sustain the drag forces on the aggregate determines whether it remains intact or sheds individual platelets or larger fragments (emboli). We investigate platelet aggregation in coronary-sized arteries using both computational simulations and in vitro experiments. The computational model tracks the formation and breaking of bonds between platelets and treats the thrombus as an evolving porous, viscoelastic material, which moves differently from the background fluid. This relative motion generates drag forces which the fluid and thrombus exert on one another. These forces are computed from a permeability-porosity relation parameterized from experimental measurements. Basing this relation on measurements from occlusive thrombi formed in our flow chamber experiments, along with other physiological parameter values, the model produced stable dense thrombi on a similar timescale to the experiments. When we parameterized the permeability-porosity relation using lower permeabilities reported by others, bond formation was insufficient to balance drag forces on an early thrombus and keep it intact. Under high shear flow, soluble agonist released by platelets was limited to the thrombus and a boundary layer downstream, thus restricting thrombus growth into the vessel lumen. Adding to the model binding and activation of unactivated platelets through von Willebrand-factor-mediated processes allowed greater growth and made agonist-induced activation more effective.

Dataset Information

Simulation of intrathrombus fluid and solute transport using in vivo clot structures with single platelet resolution.

Publications

Simulation of intrathrombus fluid and solute transport using in vivo clot structures with single platelet resolution.

Similar Datasets

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