Post-occlusive Reactive Hyperemia in Mouse Melanoma

Abstract

Post-occlusive reactive hyperemia (PORH) is a physiological reaction characterizing the vascular reactivity to application and cessation of blood flow occlusion. Increasing evidence indicates that the PORH may reduce tumor hypoxia and could be used as a clinically relevant method to improve the efficiency of conventional anti-cancer therapies. In order to experiment this new concept, we developed a simple and reproducible mouse model of skin PORH using a leg tourniquet to produce temporary vascular occlusion. Footpad superficial perfusion was continuously measured by laser speckle contrast imaging. We then analyzed the incidence of PORH on B16-F10 melanomas cells injected in the footpad skin. The mouse model reproduced the characteristics of the skin PORH in humans, with a close relationship between the duration of the vascular occlusion and the hyperemia amplitude as well as extent. We also unravelled that PORH also occurred in growing melanoma with a significant 48% median hyperemia after three minutes of vascular occlusion. We therefore described for the first time a PORH phenomenon in a locally very advanced and necrotic murine melanoma that may pave the way for the development of complementary therapeutic approaches to dampen the growth of aggressive tumors.