Microthrombosis induced by mechanical factors and light/dye treatment in intact microvessels

Thrombosis is the formation of a blood clot in a blood vessel. When thrombosis happens in the brain, it would cause stroke; when happens in the heart, it would cause heart attack. If a thrombus travels to the lung, it would cause pulmonary embolism and lead to death under certain circumstances. Although both chemical and mechanical factors can induce thrombosis, the quantitative understanding of the contribution from mechanical factors is poor, especially in the microvasculature with non-disturbed laminar flows. The first part of this study thus investigated the relation between localized shear rates/stresses and thrombosis in bent microvessels with low Reynolds number blood flows. In vivo experiments on microvessels in rat mesentery revealed that thrombi were initiated at the inner wall of the bent vessel, while computational results demonstrated that there was a higher shear stress/rate and a higher shear stress/rate gradient at the inner wall of the bent vessel, which could activate endothelial and blood cells for binding. These results suggest that the higher shear stress/rate and the higher shear stress/rate gradient are the mechanical factors inducing thrombi in the microvessels with very low Reynolds number flows.;Photodynamic therapy (PDT) is a treatment that uses a photosensitizer (photosensitizing agent) excited by a specific wavelength light to treat various diseases including tumors. However, PDT also induces thrombosis in the blood vessels of normal tissues adjacent to the tumor. To search for a preventive method for unwanted thrombosis, in the second part of the study, we examined the structural mechanisms by which light/dye treatment induces microvascular hyperpermeability and thrombosis. In vivo experiments showed that under the similar light/dye treatment, microvessel thrombosis and hyperpermeability were highly correlated with each other. Comparison of the measured permeability data with predictions from a mathematical model for the inter-endothelial cleft suggests that an almost complete depletion of the glycocalyx layer at the luminal surface of the endothelium is the most likely structural mechanism by which the light/dye increases microvascular permeability and induces thrombosis. If the light/dye degrades the surface glycocalyx to increase vessel permeability, the increased radial fluid flow across the microvessel wall would bring platelets and leukocytes closer to the proximity of the wall and enhance the opportunity of their binding to endothelium. In addition, removing the surface glycocalyx would expose endothelium for the binding.