title: The shunt problem: control of functional shunting in normal and tumour vasculature.
abstract: Networks of blood vessels in normal and tumour tissues have heterogeneous structures, with widely varying blood flow pathway lengths. To achieve efficient blood flow distribution, mechanisms for the structural adaptation of vessel diameters must be able to inhibit the formation of functional shunts (whereby short pathways become enlarged and flow bypasses long pathways). Such adaptation requires information about tissue metabolic status to be communicated upstream to feeding vessels, through conducted responses. We propose that impaired vascular communication in tumour microvascular networks, leading to functional shunting, is a primary cause of dysfunctional microcirculation and local hypoxia in cancer. We suggest that anti-angiogenic treatment of tumours may restore vascular communication and thereby improve or normalize flow distribution in tumour vasculature.
authors.affiliation: Department of Physiology and the Centre for Cardiovascular Research, Charité Berlin, Thielallee 71, D-14195 Berlin, Germany. axel.pries@charite.de
authors.forename: Axel R
authors.initials: AR
authors.lastname: Pries
authors.forename: Michael
authors.initials: M
authors.lastname: Höpfner
authors.forename: Ferdinand
authors.initials: F
authors.lastname: le Noble
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Secomb
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D003198:Computer Simulation; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D055806:Microvessels / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply*; D012039:Regional Blood Flow; D015398:Signal Transduction