Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients.
OBJECTIVE
Inflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy. We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI).


METHODS
Randomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO(2)) <40 mmHg and/or toe pressure <50 mmHg received placebo (n=74) or a non-specific immunomodulation therapy (IMT) (n=77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO(2), levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-alpha-TNF-alpha).


RESULTS
TcPO(2) and CD34/CD133-positive cells increased at 22 weeks in IMT group (P<0.01) whereas no changes were observed in placebo group. TNF-alpha levels decreased at 6 months in IMT group (P<0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO(2) (r=0.56, P<0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-alpha (r=-0.51, P<0.01).


CONCLUSIONS
Intramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.
Marfella
Raffaele
R
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Piazza Miraglia, 2. 80138 Napoli, Italy. raffaele.marfella@unina2.it
Luongo
Carlo
C
Coppola
Antonino
A
Luongo
Margherita
M
Capodanno
Paola
P
Ruggiero
Roberto
R
Mascolo
Luigi
L
Ambrosino
Immacolata
I
Sardu
Celestino
C
Boccardi
Virginia
V
Lettieri
Biagio
B
Paolisso
Giuseppe
G
D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis; D042783:Endothelial Cells; D005121:Extremities / Q000098:blood supply / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006439:Hemodynamics; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation; D007511:Ischemia / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D010100:Oxygen / Q000737:chemistry*; D010126:Ozone; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014456:Ulcer / Q000473:pathology* / Q000628:therapy; D014945:Wound Healing
D018952:Antigens, CD34; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone; D010100:Oxygen