| Objective Photodynamic therapy (PDT) is now becoming a more accepted form of treatment on small superficial tumors and some hyperplasic disease, such as port wine stain (PWS) and age-related macular degeneration (AMD). Damage to microcirculation of target tissue during and after PDT is more and more realized. However, there have been few dynamic measurements of the acute changes in the microcirculation during PDT and few quantitative studies on the type or size of vessels. The objective of this study is to gain an understanding of the changes in the microcirculation during and after photodynamic therapy in detail, to compare the effect of microvasculature with different RBCs Column Diameter and blood flow rate, and to assess the relationship between the dose of photosensitizer and the injury of microcirculation.Methods & Results 1. Study on effect regularity of photodynamic therapy on rats mesenteric microcirculation: (1) Establishment and assessment of microcirculation research methods: The rat mesenteric microcirculation model was used in this study. The classic microcirculation method using intravital microscopy was improved on in order to meet the especial request of this experiment. A 532nm KTP laser with a fiberoptic light delivery system was used to illuminate a 0.6 cm diameter field centered in the rats mesentery and the power density of light was measured by a thermopile. The diameter of the column of RBCs(RBCCD), blood flow velocity(BFV) and blood flow states(BFS) in microvasculature were measured to estimate the stability of the methods. Results showed that the use of the improved intravital microscopy of mesenteric microcirculation allow us to measure in detail the changes in small blood vessel during 2 h and the rats did not show any changes. There were not significant drops in the RBCCD, BFV and BFS(P>0.05). The maximum power output of laser was 112.6mW, the fluctuation was ±0..02 mW. The maximumpower output of the end of the fiber was 81.1mW. (2) Study of photodynamic effect on rats mesenteric microcirculation: intravital microscopy was used to observe the changes in the rats mesenteric microcirculation during photodynamic therapy using three photosensitisers respectively, hematoporphyrin derivative(HpD), hematoporphyrin monometheyl ether (HMME) or hypocrellin B(HB) and to assess the relationship between the dose of PDT and the injuries of microcirculation. Results showed that the mesenteric microcirculation vascular endothelial cells swell, erythrocytes were aggregated, and leucocytes were stuck to vessel wall, mural platelet thrombi formed during PDT. White emboli were observed forming on the inside of the vessel walls within seconds after commencement of light exposure. Emboli adhered to vessel walls and caused vascular obstruction, the diameter of the column of RBCs and blood flow velocity decreased and led to the relative measure of the degree of blood flow stasis. The stasis time was influenced by drug dose and laser dose. With lower drug dose?it took a longer time to injure the microvasculature. The doses of HpD were 0.5, 1.0, 1.5, 2.0mg/kg, the percentages of RBCCD after PDT were 70%, 0, 0, 0 respectively; The doses of HMME were 2.5, 5, 10, 15, 20mg/kg, the percentages of RBCCD after PDT were 42%, 30%, 21%, 0, 0 respectively; The doses of HB were 2,4, 6, 8mg/kg, the percentages of RBCCD after PDT were 88%, 67%, 14%, 0 respectively. There have no significant differences between PDT injuries using three different photosensitizers. (3) Study of microvascular sensibility to PDT: The rats mesenteric microcirculation model was used in this study. The PDT injury effects of different microvasculature were compared by intravital microscopy. Results stated that PDT had the most severe injuries to capillary and the greatest influence on its RBCCD decline speed. And these effects weakened in order of venule, arteriole, small vein and small artery. During HpD-PDT, the stasis times of microvasculature were 6, 16, 18, 22, 26min; During HMME-PDT, the stasis times of microvasculature were 6, 18,...
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