Stimulation of Angiogenesis in Rat Ischemic Limb by Intramuscular Implantation of Mononuclear Fraction Cells from Autologous Bone Marrow
ABSTRACT We studied angiogenic effects of two variants of indirect revascularization (transplantation of mononuclear fraction cells
from autologous bone marrow alone or in combination with laser tunneling) after modeled ischemia of the lower limbs in rats.
Doppler sonography and immunofl uorescence studies showed that intramuscular implantation of isolated fraction of autologous
bone marrow mononuclear cells in combination with laser tunneling of the muscles is most effective and can be recommended
as a method of angiogenesis stimulation in nonreconstructable distal vascular pathology of the extremities.
Key Wordsischemia of extremities–revascularization–bone marrow mononuclear fraction–laser tunneling of muscles–immunofluorescence
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ABSTRACT: The purpose of the present study was to compare the effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators on the oscillatory components of the cutaneous blood perfusion signals in humans. The unstimulated basal blood perfusion and the blood perfusion during iontophoretically delivered ACh and SNP were measured using laser Doppler flowmetry (LDF). The wavelet transform was calculated before spectral analysis of the measured signals. In the frequency interval from 0.0095 to 1.6 Hz the LDF signal consists of oscillations with five different characteristic frequencies. In addition to the cardiac (1 Hz) and respiratory (0.3 Hz) rhythms, three other oscillations in the regions around 0.1, 0.04, and 0.01 Hz were detected. The oscillations with the different frequencies were observed in unstimulated blood flow and also during stimulation with ACh and SNP. Compared to the unstimulated blood flow, both ACh and SNP increased the mean amplitude of the total spectrum (P < 0. 005 for both substances). The only significant difference between the effects of ACh and SNP was observed in the amplitude of oscillations with the frequency of around 0.01 Hz. ACh increased the absolute amplitude of this frequency to a greater extent than SNP in athletes (P = 0.03), whereas only a trend was observed in controls (P = 0.2). The relative amplitude, defined as the ratio between the absolute amplitude of a particular frequency interval and the mean amplitude of the total spectrum, was also higher for ACh compared to SNP both in controls (P = 0.008) and in athletes (P = 0.004), only for oscillations with the frequency of around 0.01 Hz. We conclude that ACh selectively influences the oscillatory component of around 0.01 Hz in the cutaneous blood perfusion signal to a greater extent than SNP. This finding indicates that endothelium-mediated vasodilatation is manifested as oscillations with a repetition time of approximately 1 min. The mechanisms for the endothelial dependency of this frequency remain to be elucidated. Our data indicate that spectral analysis based on wavelet transform of the cutaneous perfusion signal can be used clinically to investigate endothelial function. The described noninvasive method might be used to evaluate endothelial function for research, for diagnostic purposes, and maybe also to assess effects of therapy in cardiovascular diseases.Microvascular Research 05/1999; 57(3):298-309. DOI:10.1006/mvre.1998.2139 · 2.43 Impact Factor
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ABSTRACT: Short-term (within 6 weeks follow-up) clinical studies indicate that implantation of bone marrow cells (BMCs) into ischemic limbs may improve peripheral ischemia. Here, the long-term safety and feasibility of intraarterial autologous BMCs with oral treatment with antioxidants and L-arginine were investigated in patients with critical ischemia on account of advanced atherosclerotic peripheral arterial disease (PAD). Eighteen patients with PAD (advanced III/IV Fontaine stages) were enrolled in this study (NCT00306085). An additional group of 18 patients taking maximal drug therapy that refused BMC therapy served as control. The BMC-treated group received two doses of BMCs in the leg arteries (time 0 and 45 days). After 30 days from the first BMC dose, patients received daily antioxidants, and L-arginine. Therapeutic neoangiogenesis was estimated by angiography and laser Doppler\capillaroscopy. Ankle brachial index improvement (DeltaABI: >0.1) was seen in 10 patients at 3 months and in 12 patients at 12-18 months. Ischemic ulcers improved in 13 patients (after 6-12 months). Although two patients underwent amputation, the mean maximum walking distance significantly increased at 3 months and was sustained up to 18 months. Among conservative patients, 10 underwent amputation in comparison with two BMC-treated patients (55.6 vs. 13.3%; P=0.014). This small study shows that intraarterial autologous BMC and antioxidants and L-arginine therapy is safe and effective in patients with advanced atherosclerotic PAD with positive effects until 18 months.European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 01/2009; 15(6):709-18. DOI:10.1097/HJR.0b013e3283193a0f · 3.69 Impact Factor