Objective To examine the temporal integration of vascular endothelial
growth factor (VEGF), which has been shown to be present in wound flui
d, with the putatively related processes of wound fluid oxygen content
, wound angiogenesis, and granulation tissue formation. Summary Backgr
ound Data During cutaneous wound repair, new tissue formation starts w
ith reepithelialization and is followed by granulation tissue formatio
n, including neutrophil and macrophage accumulation, fibroblast ingrow
th, matrix deposition, and angiogenesis. Because angiogenesis and incr
eased vascular permeability are characteristic features of wound heali
ng, VEGF may play an important role in tissue repair. Methods A ventra
l hernia, surgically created in the abdominal wail of female swine, wa
s repaired using silicone sheeting and skin closure. Over time, a flui
d-filled wound compartment formed, bounded by subcutaneous tissue and
omentum. Ultrasonography was performed serially to examine the anatomy
and dimensions of the subcutaneous tissue and wound compartment. Seri
al wound fluid samples, obtained by percutaneous aspiration, were anal
yzed for Po-2, Pco(2), pH, and growth factor concentrations. Results T
hree independent assays demonstrate that VEGF protein is present at su
bstantially elevated levels in a wound fluid associated with the forma
tion of abdominal granulation tissue. However, the wound fluid is not
hypoxic at any time. Serial sampling reveals that transforming growth
factor beta-1 protein appears in the wound fluid before VEGF. Conclusi
ons The results suggest that VEGF is a prominent regulator of wound an
giogenesis and vessel permeability. A factor other than hypoxia, perha
ps the earlier appearance of another growth factor, transforming growt
h factor beta-1, may positively regulate VEGF appearance in the wound
fluid.