Skin capillary permeability in the diabetic foot with critical limb ischaemia: the effects of a phVEGF165 gene product.
OBJECTIVE
To measure capillary permeability, assessed by skin capillary sodium fluorescein (NaF) leakage, in patients with diabetes mellitus with critical limb ischaemia (DM-CLI) and to compare the effects of vascular endothelial growth factor (VEGF) with those of placebo.


METHODS
NaF leakage was assessed in 17 patients with DM-CLI, in 24 diabetes mellitus (DM) patients without clinical signs of macrovascular disease or neuropathy (DM-C) and in 22 healthy control subjects. The 17 DM-CLI patients were randomized to receive phVEGF165 gene product (n = 11) or placebo (n = 6). Measurements were repeated after 28 days.


RESULTS
DM-CLI patients had a longer dye arrival time (DAT), but NaF leakage was similar to control subjects, while capillary permeability was increased in DM-C compared with control subjects. Leakage curve rose in patients receiving VEGF and fell in those receiving placebo, 28 days after administration. The decrease in DAT in the VEGF group was not significant, whilst DAT rose in the placebo group. Perfusion pressures were similar in the two groups.


CONCLUSIONS
No increase in capillary leakage in DM-CLI was found, probably because an increased capillary filtration coefficient is counterbalanced by a marked fall in perfusion pressures. Increased capillary leakage may be one explanation for oedema formation after VEGF treatment.
de Leeuw
K
K
Department of Internal Medicine, Divisions of Rheumatology and Clinical Immunology, University Medical Center, Groningen, Groningen, The Netherlands. k.de.leeuw@int.umcg.nl
Kusumanto
Y
Y
Smit
A J
AJ
Oomen
P
P
van der Hoeven
J H
JH
Mulder
N H
NH
Hospers
G A P
GA
D000368:Aged; D002196:Capillaries / Q000503:physiopathology; D002199:Capillary Permeability; D016022:Case-Control Studies; D017719:Diabetic Foot / Q000188:drug therapy / Q000503:physiopathology*; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000627:therapeutic use; D005260:Female; D019793:Fluorescein; D005456:Fluorescent Dyes; D005528:Foot; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use
D016228:Endothelial Growth Factors; D005456:Fluorescent Dyes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019793:Fluorescein