Simulation of Plasmatic Enzyme Reactions During Thrombolytic Therapy With Recombinant Tissue-Type Plasminogen Activator: from In Vitro Knowledge To New Assumptions In Vivo

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Abstract
Therapy of occlusive pathologies of blood vessels, like acute myocardial infarction, is commonly based on administration of thrombolytic enzymes that accelerate the dissolution of thrombi, but that increase also the risk of bleeding through their activity on specific plasma substances. In order to gain insight regarding the relative importance of various processes on the dynamics of these plasma substances we developed a math ematical model of biochemical reactions occurring in plasma during therapy with the thrombolytic agent rt-PA ( recombinant tissue-type Plasminogen Activator). On the basis of in vitro knowledge a preliminary model was formulated and simulation studies were performed to analyze in detail the various processes. During the validation of the model some novel hypotheses emerged regarding the importance of specific biochemical reactions in vivo. A revised model was then formulated which well describes experimental observations reported in literature.