Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients

被引:22
作者
Marfella, Raffaele [1 ]
Luongo, Carlo [2 ]
Coppola, Antonino [3 ]
Luongo, Margherita [2 ]
Capodanno, Paola [2 ]
Ruggiero, Roberto [1 ]
Mascolo, Luigi [2 ]
Ambrosino, Immacolata [1 ]
Sardu, Celestino [1 ]
Boccardi, Virginia [1 ]
Lettieri, Biagio [2 ]
Paolisso, Giuseppe [1 ]
机构
[1] Univ Naples 2, Dept Geriatr & Metab Dis, I-80138 Naples, Italy
[2] Univ Naples 2, Dept Anesthesiol & Emergency, I-80138 Naples, Italy
[3] Osped S Maria Misericordia, Operat Unit Cardiol, Sorrento, Italy
关键词
Oxygen/ozone therapy; Limb ischemia; Inflammation; Endothelial cells; ENDOTHELIAL PROGENITOR CELLS; TUMOR-NECROSIS-FACTOR; KAPPA-B; ANGIOGENESIS; MOBILIZATION; DISEASE; TCPO2;
D O I
10.1016/j.atherosclerosis.2009.08.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/aims: 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 (TcPO2) <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 TcPO2, levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-alpha-TNF-alpha). Results: TcPO2 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 TcPO2 (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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:473 / 479
页数:7
相关论文
共 24 条
[21]  
TASC Working Group, 2000, EUR J VASC ENDOVASC, V19, pS1
[22]   Results of a non-specific immunomodulation therapy on chronic heart failure (ACCLAIM trial):: a placebo-controlled randomised trial [J].
Torre-Amione, Guillermo ;
Anker, Stefan D. ;
Bourge, Robert C. ;
Colucci, Wilson S. ;
Greenberg, Barry H. ;
Hildebrandt, Per ;
Keren, Andre ;
Motro, Michael ;
Moye, Lemuel A. ;
Otterstad, Jan Erik ;
Pratt, Craig M. ;
Ponikowski, Piotr ;
Rouleau, Jean Lucien ;
Sestier, Francois ;
Winkelmann, Bernhard R. ;
Young, James B. .
LANCET, 2008, 371 (9608) :228-236
[23]   Evidence for ozone formation in human atherosclerotic arteries [J].
Wentworth, P ;
Nieva, J ;
Takeuchi, C ;
Galve, R ;
Wentworth, AD ;
Dilley, RB ;
DeLaria, GA ;
Saven, A ;
Babior, BM ;
Janda, KD ;
Eschenmoser, A ;
Lerner, RA .
SCIENCE, 2003, 302 (5647) :1053-1056
[24]  
Yamahara Kenichi, 2009, Ther Adv Cardiovasc Dis, V3, P17, DOI 10.1177/1753944708097728