Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat

Purpose: The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction. Methods and Materials: Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. L eukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irra diation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expressi on were measured using radiolabeled monoclonal antibodies. Results: Low dose-rate (LDR) abdominal irradiation increased leukocyte adhe sion compared with sham-irradiated animals, whereas high dose-rate (HDR) ir radiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increa sed microvascular permeability, although this effect was significantly grea ter after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expres sion in splanchnic organs than LDR, whereas in most organs ICAM-1 expressio n was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates. Conclusions: The magnitude of upregulation of endothelial adhesion molecule s, leukocyte recruitment, and endothelial barrier dysfunction elicited by r adiation therapy is dependent on the dose-rate at which the radiation is de livered. (C) 1999 Elsevier Science Inc.