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Changed microvascular adaptation characteristics may explain heterogeneity and hypoxia of tumor perfusion
Author(s) -
Pries Axel R,
Cornelissen Annemiek JM,
Sloot Anouk A,
Dreher Matthew,
Hinkeldey Marlene,
Höpfner Michael,
Dewhirst Mark W,
Secomb Timothy W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.925.6
Subject(s) - microcirculation , hemodynamics , hypoxia (environmental) , perfusion , adaptation (eye) , intravital microscopy , metabolic adaptation , biology , chemistry , biophysics , medicine , neuroscience , oxygen , metabolism , organic chemistry
Tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxia and impairing treatment efficacy. Structural properties of normal vascular beds are controlled by continuous adaptation to local hemodynamic and metabolic stimuli. Here, we tested the hypothesis that tumor microvascular properties are due to changed vascular adaptation characteristics. Control and tumor vascular networks were recorded by intravital microscopy. Hemodynamics and oxygen distribution in these networks were assessed by computer modeling. Vascular diameter adaptation in response to hemodynamic, metabolic and conducted stimuli was simulated. Results were analyzed with respect to diameter heterogeneity at individual bifurcations (A D ) and deficit of oxygen delivery relative to demand (O def ). Tumor networks (T) exhibit high A D (0.40) and O def (0.17) as compared to control networks (C) (A D 0.28; O def 0.10). Simulated adaptation of T with previously established vascular reaction characteristics of normal tissues led to normalized values for T (A D 0.32; O def 0.11). In turn, C could be made to mimic T characteristics by assuming increased randomness of vascular growth tendency and by reducing sensitivity to conducted stimuli (A D 0.41; O def 0.17). Thus, aberrant properties of tumor microvasculature can be explained by changed vascular adaptation characteristics.