Normoxic Wound Fluid Contains High Levels of Vascular Endothelial Growth Factor

Howdieshell, Thomas R.; Riegner, Charlton; Gupta, V. K.; Callaway, Dianne; Grembowicz, Ken; Sathyanarayana,; McNeil, Paul L.

doi:10.1097/00000658-199811000-00011

Cited by 62 publications

(48 citation statements)

References 27 publications

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“…The initially increased permeability as well as LEIs after bone chamber implantation are likely due to the surgical manipulation at the cortical bone with cell injuries and consecutive aseptic inflammatory reaction [ 1 1,16, 24,33,57,63]. The decrease in these parameters to a steady state reflects therefore the return to the normal microcirculatory environment, which was reached 12 days after femur window implantation and should be considered using a chamber implantation for longterm observations.…”

Section: Discussionmentioning

confidence: 99%

Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt

Schaefer

Wolfram

et al. 2005

Journal Orthopaedic Research

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Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis.Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIS) in femoral bone tissue of c57-black mice ( n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested.Results: Microvascular permeability and LEIS showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion:The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis.

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Section: Discussionmentioning

confidence: 99%

Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt

Schaefer

Wolfram

et al. 2005

Journal Orthopaedic Research

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“…Based on this evidence, we conclude that hypoxia is not responsible for the initial triggering of the repair and angiogenesis cascade. Recently, Howdieshell et al 38 have shown that wound fluid obtained from abdominal wounds was normoxic, although they detected high levels of cytokine (VEGF and TGF␤) expression.…”

Section: Discussionmentioning

confidence: 99%

Early Wound Healing Exhibits Cytokine Surge Without Evidence of Hypoxia

Haroon¹,

Raleigh²,

Greenberg³

et al. 2000

Annals of Surgery

108

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ObjectiveTo ascertain the spatial and temporal relation of wound hypoxia to the cell types involved, expression of selected angiogenic cytokines, the proliferative status of cells in the wound site, and angiogenesis. Summary Background DataHypoxia is considered to drive the angiogenic response by upregulating angiogenic cytokines observed during wound healing. But this correlation has not been shown on a cell-tocell basis in vivo because of limitations in measuring tissue PO 2 at the cellular level. MethodsUsing punch biopsy wounds in rats as a wound healing model, the distributions of vascular endothelial growth factor, transforming growth factor-beta, tumor necrosis factor-alpha, and pimonidazole adducts (as a hypoxia marker) were followed immunohistochemically during the healing process.

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“…It is present in wound fluid in high concentrations (Howdieshell et al 1998), and it is secreted by different cell types in response to keratinocyte growth factor (KGF), TGF-␤ Ferrara 1995), hypoxia (Shweiki et al 1992), bFGF (Stavri et al 1995) and PDGF (Frank et al 1995). Platelets are one of the first cells to appear in the wound site followed by neutrophils and macrophages.…”

Section: Phase Iiia: Angiogenesismentioning

confidence: 99%