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Computer simulation of systemic circulation and clot lysis dynamics during thrombolytic therapy that accounts for inner clot transport and reaction.

Abstract：

BACKGROUND:We developed a computer model to predict lysis rates of thrombi for intravenous thrombolytic regimens based on the convective/diffusive penetration of reacting and adsorbing fibrinolytic species from the circulation into the proximal face of a dissolving clot. METHODS AND RESULTS:Solution of a one-compartment plasma model provided the dynamic concentrations of fibrinolytic species that served as inlet conditions for stimulation of the one-dimensional spatiodynamics within a dissolving fibrin clot of defined composition. The model predicted the circulating levels of tissue plasminogen activator (TPA) and plasminogen levels found in clinical trials for various intravenous therapies. To test the model predictions under in vitro conditions, plasma clots were perfused with TPA (0.1 mumol/L) and plasminogen (1.0 mumol/L) delivered at constant permeation velocity of 0.1 or 0.2 mm/min. The model provided an accurate prediction of the measured lysis front movement. For TPA administration regimens used clinically, simulations predicted clot dissolution rates that were consistent with observed reperfusion times. For unidirectional permeation, the continual accumulation of adsorbing species at the moving lysis front due to prior rounds of solubilization and rebinding was predicted to provide for a marked concentration of TPA and plasmin and the eventual depletion of antiplasmin and macroglobulin in an advancing (approximately 0.25 mm thick) lysis zone. CONCLUSIONS:Pressure-driven permeation greatly enhances and is a primary determinant of the overall rate of clot lysis and creates a complex local reaction environment at the plasma/clot interface. With simulation of reaction and transport, it becomes possible to quantitatively link the administration regimen, plasminogena activator properties, and thrombolytic outcome.

journal_name

Circulation

journal_title

Circulation

authors

Anand S,Diamond SL

doi

10.1161/01.cir.94.4.763

subject

Has Abstract

pub_date

1996-08-15 00:00:00

pages

763-74

issue

eissn

0009-7322

issn

1524-4539

journal_volume

pub_type

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Computer simulation of systemic circulation and clot lysis dynamics during thrombolytic therapy that accounts for inner clot transport and reaction.