A Concept of Thrombolysis as a Corrosion–Erosion Process Verified by Optical Microscopy FRANCI BAJD,* AND IGOR SERS ˇ A *,  * Joz ˇef Stefan Institute, Ljubljana, Slovenia;   EN-FIST Centre of Excellence, Ljubljana, Slovenia Address for correspondence: Igor Sers ˇa, Ph.D., Joz ˇef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia. E-mail: igor.sersa@ijs.si Received 2 April 2012; accepted 15 May 2012. ABSTRACT Objective: Outcome of the thrombolytic treatment is dependent on biochemical reactions of the fibrinolytic system as well as on hemodynamic conditions. However, understanding of the interaction between these two processes is still deficient. Methods: Model blood clot thrombolysis in an artificial perfusion system was studied by stroboscopic optical microscopy. The obtained images were analyzed by particle-tracking software for clot size distributions of removed clot fragments, and for non-lysed blood clot areas as function of time. Based on the experimental results, a probabilistic phenomenological model of blood clot dissolution was developed, in which mechanical forces of streaming plasma are in balance with binding forces of blood cells to the remaining clot. Results: The clot dissolution rate and maximum size of removed clot fragments were increased with greater flow rate. A 3.3-fold flow rate increase resulted in a two-fold clot dissolution rate increase, while sizes of the removed fragments were in the range of single blood cells, up to thousand-cell clusters. Our phenomenological microscale model of clot dissolution suggests that thrombolysis is a corrosion–erosion-like process. Conclusions: The findings of this study provide a possible explanation for the origin of clot fragment formation in the blood clot dissolution process. Key words: blood clot, microcirculation, probabilistic modeling, stroboscopic optical microscopy, thrombolysis Abbreviations used: CCD, charge-coupled device; FOV, field of view; NCD, normalized clot dissolution curve; NCFS, normalized clot fragment size distribution; NIH unit, National Institutes of Health unit (1 NIH unit = 0.324 ± 0.073 lg); rt-PA, recombinant tissue plasminogen activator. Please cite this paper as: Bajd F, Sers ˇa I. A concept of thrombolysis as a corrosion–erosion process verified by optical microscopy. Microcirculation 19: 632–641, 2012. INTRODUCTION The aim of thrombolytic therapy is the efficient dissolution of obstructing blood clots, and thus the restoration of ves- sel patency. Thrombolysis is widely used in treatment of ischemic cerebrovascular stroke [14,30], critical limb ische- mia [9], pulmonary embolism [13], and acute arterial thrombosis [12]. The biochemical basis of thrombolysis is proteolysis of the fibrin network that entraps blood cells [8]. Thrombolysis is triggered by conversion of the inactive proenzyme plasminogen into the active serine protease plasmin by plasminogen activators, e.g., rt-PA. Plasmin acts locally on the fibrin polymer, whereas in circulating plasma, it is rapidly inactivated by its specific inhibitor antiplasmin [8]. Several mathematical models [18,31] and experiments [20,21,23,26] on dissolution of non-occlusive blood clots in model perfusion systems as well as clinical results [4] indicate that the rate of thrombolysis significantly depends on blood flow streaming axially along the clot. The effect of blood flow is not only a better permeation of a blood clot with the thrombolytic agent but also an emergence of shear forces that mechanically degrade and erode the clot surface. We have proposed earlier that higher mechanical forces of rapidly streaming plasma remove bigger and only partially chemically degraded fragments from the clot sur- face, while lower forces of slowly flowing plasma remove considerably smaller clot fragments that may be chemically degraded down to single blood cells [24]. However, analysis of fibrin degradation products by gel electrophoresis [15] in relation to the rate of axially directed plasma flow did not prove suitable, as the abundance of plasma proteins dwarfed the minute quantities of fibrin degradation prod- ucts and prevented their detection by biochemical methods. An interesting alternative to the study of thrombolysis by analysis of fibrin degradation products on the molecular DOI:10.1111/j.1549-8719.2012.00198.x Original Article 632 ª 2012 John Wiley & Sons Ltd The Official Journal of the Microcirculatory Society, Inc. and the British Microcirculation Society