Microvascular hyperpermeability and thrombosis induced by light/dye treatment

Abstract

To investigate microvascular hyperpermeability and thrombosis induced by photodynamic therapy or light/dye treatment, we quantified the initiation time for thrombus formation, thrombus growth rate, and the time for the microvessel occlusion in post-capillary venules of rat mesenteries. Under similar light/dye treatments, we also measured the microvessel hydraulic conductivity (Lp) and solute permeability (P) to TRITC-BSA (bovine serum albumin), respectively, in the same type of microvessels as for thrombosis. Under an irradiation power of 0.37mW/mm(2), thrombus was initiated in 3.8 ± 0.4min, its growth rate was 3.9 ± 0.3% of the vessel mid-plane area/min, and the microvessels were completely occluded in 29.3 ± 2.2min (SE, n=8). Under the same irradiation power, Lp and P increased gradually, reaching a plateau in 3-5min. At the plateau, Lp had increased to 2.2 ± 0.2times (n= 11), while P had increased to 4.1 ± 0.7 (n=7) times their baseline values, respectively. Neither Lp nor P increased further after longer time exposure (up to 30min). Comparison of the measured Lp and P 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 might be one of the structural mechanisms by which the light/dye increases microvascular permeability and induces thrombosis.