Microvascular hyperpermeability and thrombosis induced by light/dye treatment.
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 0.37 mW/mm(2), thrombus was initiated in 3.8 ± 0.4 min, its growth rate was 3.9 ± 0.3% of the vessel mid-plane area/min, and the microvessels were completely occluded in 29.3 ± 2.2 min (SE, n = 8). Under the same irradiation power, Lp and P increased gradually, reaching a plateau in 3-5 min. At the plateau, Lp had increased to 2.2 ± 0.2 times (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 30 min). 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.
Liu
Qin
Q
Department of Biomedical Engineering, The City College of the City University of New York, 140th Street & Convent Ave., New York, NY 10031, USA.
Zeng
Min
M
Fu
Bingmei M
BM
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000528:radiation effects; D002199:Capillary Permeability / Q000187:drug effects* / Q000528:radiation effects*; D004396:Coloring Agents / Q000494:pharmacology*; D005260:Female; D019793:Fluorescein / Q000494:pharmacology; D008027:Light; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000378:metabolism; D013927:Thrombosis / Q000503:physiopathology*; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000503:physiopathology
D000418:Albumins; D004396:Coloring Agents; D012235:Rhodamines; C009434:tetramethylrhodamine isothiocyanate; D019793:Fluorescein