Photobiomodulation Therapy to Promote Angiogenesis in Diabetic Mice with Hindlimb Ischemia.

Objective: To assess whether photobiomodulation therapy (PBMT) induces angiogenesis in diabetic mice with hindlimb ischemia (HLI). Background: Patients with diabetes mellitus (DM) are at high risk of developing peripheral arterial disease (PAD) in the lower extremities. PBMT has been shown to promote angiogenesis both in vitro and in vivo and could be a treatment for DM patients with PAD. Methods: Femoral artery ligation/excision in mice was performed to induce HLI as an animal model of PAD. PBMT at a dose of 660 nm and 1.91 J/cm2 was delivered for 10 min on 5 consecutive days after the HLI surgery. Control mice received HLI only. Mice in the DM group were injected with streptozocin to induce diabetes before HLI surgery. Mice in the laser and DM+ laser groups received both HLI and PBMT, and the latter group had induced DM. After the laser treatment, lower limb blood flow was evaluated by laser Doppler. The capillary density and CD31 were analyzed by immunofluorescence staining, and protein levels of vascular endothelial growth factor (VEGF)-A, hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinases (ERK) were measured by Western blotting of tissue samples. Results: Compared with the control and DM mice, the laser and DM+ laser groups had more than double the capillary density and blood perfusion rate. Levels of CD31 and VEGF-A proteins in groups that received laser were increased by 1.9- to 3.2-fold compared with groups that did not undergo laser treatment. Animals treated with PBMT exhibited significantly increased HIF-1α expression and ERK phosphorylation compared with animals that did not receive this treatment, and the amount of phospho-eNOS and iNOS increased and decreased, respectively. Conclusions: PBMT can induce therapeutic angiogenesis, indicating that low intensity laser could be a novel treatment for PAD patients.

Effects of prenatal photobiomodulation treatment on neonatal hypoxic ischemia in rat offspring.

Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Effects of Photobiomodulation on Degranulation and Number of Mast Cells and Wound Strength in Skin Wound Healing of Streptozotocin-Induced Diabetic Rats.

BACKGROUND: A lack of effective treatments still exists for patients suffering from diabetes mellitus. Photobiomodulation is proved as a beneficial therapeutic modality for wounds. OBJECTIVE: The aim of this study is to examine the effect of degranulation of mast cells and total number of mast cells in the remodeling step of an ischemic model of wound healing under the influence of photobiomodulation and conditioned medium (CM) from human bone marrow-derived mesenchymal stem cells (hBM-MSCs-CM), or CM, administered alone and or in combination. MATERIALS AND METHODS: Initially, type 1 diabetes mellitus was induced in 72 male adult rats. Then, after a month, one incision was made on the back of each rat. Subsequently, the rats were divided into four groups. The first group was considered as the control (placebo) group, the second group received CM, the third group received photobiomodulation, and the fourth group received photobiomodulation+CM. On days 4, 7, and 15, samples were extracted from the wound for histological and tensiometric examinations. The total number of mast cells, including the three types of mast cells, was counted by the stereological methods. The tensiometric properties of the repairing tissue were examined. RESULTS: The administration of photobiomodulation and CM, alone or in combination, significantly increased the tensiometric properties within the healing wounds. Histologically, photobiomodulation+CM, CM, and photobiomodulation groups showed a significant decrease in the three types of mast cells and in the total number of mast cells compared with the control group on day 15. CONCLUSIONS: We conclude that photobiomodulation and CM alone and or in combination significantly accelerated the healing process in a rat with a diabetic and ischemic wound, and significantly decreased the total number of mast cells and degranulation of mast cells. We suggest that the increased number of type 2 mast cells in the control group adversely affected the tensiometric properties of wounds in this group.

Effect of 810 nm Near-Infrared Laser on Revascularization of Ischemic Flaps in Rats.

OBJECTIVE: To investigate the effect of 810 nm near-infrared (NIR) laser on the revascularization of ischemic flaps. BACKGROUND: It has long been proved that photobiomodulation therapy (PBMT) improves the blood supply of flaps. NIR laser improves the treatment of hypodermis-located lesions and of flap survival, but basic research on the use of 810 nm NIR laser for ischemic flap revascularization is still lacking. MATERIALS AND METHODS: We prepared two symmetrical long random-pattern flaps on the backs of 60 rats. Each flap was 6 cm long, 1 cm wide, and 1 cm to the middle line. The flaps were divided into an irradiated flap group and an internal control group. The irradiated flaps underwent postoperative 810 nm laser therapy with the energy density of 11.30 J/cm2 daily. The control flaps were covered by stainless steel to avoid laser irradiation. We observed the viability of the flaps. The flaps underwent Hematoxylin and Eosin (H&E) staining for the observation of histomorphology, immunohistochemical staining of factor VIII for the capillary count, α-smooth muscle actin for the small arterial count, and vascular endothelial growth factor for the integrated optical density (OD) of the positive stained color. RESULTS: The irradiated flaps showed significantly better flap survival than the control flaps. H&E staining showed that the irradiated flaps had clear tissue structure and little inflammatory cell infiltration. The control flaps demonstrated comparatively worse results. Vascular endothelial growth factor staining showed that the difference in integrated OD between the irradiated flaps and the control flaps was not statistically significant. α-smooth muscle actin and factor VIII staining showed significantly greater numbers of arterioles and capillaries in the irradiated flaps than the control flaps after 4 days of irradiation. CONCLUSIONS: PBMT with 810 nm NIR laser could enhance ischemic flap revascularization and increase flap viability.

Enhanced survival of ischemic skin flap by combined treatment with bone marrow-derived stem cells and low-level light irradiation.

The aim of this study is to examine the enhanced survival effect of ischemic skin flap by combined treatment with bone marrow-derived stem cells (BMSCs) and low-level light irradiation (LLLI). The neovasculogenic effect of BMSCs induced by LLLI was detected using a wound healing and tube formation assay. ICR mice were divided into four groups: control group, LLLI group, BMSCs group, and combine-treated group. The percentage of skin flap necrosis area was calculated on the seventh post-operative day. Specimens were harvested for histologic analyses. LLLI promoted BMSC migration and tube formation. The flap survival rate of combined treated group was significantly higher than that of the control group. Histologic results demonstrated a significant increase in neovascularization in the combined treatment group. This study demonstrates that combination treatment of BMSCs and LLLI could enhance the survival of ischemic skin flap in a mouse model.

Low-dose ionizing radiation induces therapeutic neovascularization in a pre-clinical model of hindlimb ischemia.

AIMS: We have previously shown that low-dose ionizing radiation (LDIR) induces angiogenesis but there is no evidence that it induces neovascularization in the setting of peripheral arterial disease. Here, we investigated the use of LDIR as an innovative and non-invasive strategy to stimulate therapeutic neovascularization using a model of experimentally induced hindlimb ischemia (HLI). METHODS AND RESULTS: After surgical induction of unilateral HLI, both hindlimbs of female C57BL/6 mice were sham-irradiated or irradiated with four daily fractions of 0.3 Gy, in consecutive days and allowed to recover. We demonstrate that LDIR, significantly improved blood perfusion in the murine ischemic limb by stimulating neovascularization, as assessed by laser Doppler flow, capillary density, and collateral vessel formation. LDIR significantly increased the circulating levels of VEGF, PlGF, and G-CSF, as well as the number of circulating endothelial progenitor cells (EPCs) mediating their incorporation to ischemic muscles. These effects were dependent upon LDIR exposition on the ischemic niche (thigh and shank regions). In irradiated ischemic muscles, these effects were independent of the recruitment of monocytes and macrophages. Importantly, LDIR induced a durable and simultaneous up-regulation of a repertoire of pro-angiogenic factors and their receptors in endothelial cells (ECs), as evident in ECs isolated from the irradiated gastrocnemius muscles by laser capture microdissection. This specific mechanism was mediated via vascular endothelial growth factor (VEGF) receptor signaling, since VEGF receptor inhibition abrogated the LDIR-mediated gene up-regulation and impeded the increase in capillary density. Finally, the vasculature in an irradiated non-ischemic bed was not affected and after 52 week of LDIR exposure no differences in the incidence of morbidity and mortality were seen. CONCLUSIONS: These findings disclose an innovative, non-invasive strategy to induce therapeutic neovascularization in a mouse model of HLI, emerging as a novel approach in the treatment of critical limb ischemia patients.

Angiogenic Synergistic Effect of Adipose-Derived Stromal Cell Spheroids with Low-Level Light Therapy in a Model of Acute Skin Flap Ischemia.

Human adipose-derived mesenchymal stem cells (hASCs) are an attractive cell source for tissue engineering. However, one obstacle to this approach is that the transplanted hASC population can decline rapidly in the recipient tissue. The aim of this study was to investigate the effects of low-level light therapy (LLLT) on transplanted spheroid hASCs in skin flaps of mice. hASCs were cultured in monolayers or spheroids. LLLT, hASCs, spheroids and spheroids transplanted with LLLT were applied to the skin flaps. Healing of the skin flaps was assessed by gross evaluation and by hematoxylin and eosin staining and elastin van Gieson staining. Compared with the spheroid group, skin flap healing was enhanced in the spheroid + LLLT group, including the neovascularization and regeneration of skin appendages. The survival of hASCs was enhanced by decreased apoptosis of hASCs in the skin flaps of the spheroid + LLLT group. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASC and spheroid groups. These data suggest that LLLT was an effective biostimulator of spheroid hASCs in the skin flaps, enhancing the survival of hASCs and stimulating the secretion of growth factors.

Low level light therapy by LED of different wavelength induces angiogenesis and improves ischemic wound healing.

BACKGROUND AND OBJECTIVE: Low-level light therapy (LLLT) has been revealed as a potential means to improve wound healing. So far, most studies are being performed with irradiation in the red to near-infrared spectra. Recently, we showed that blue light (470 nm) can significantly influence biological systems such as nitric oxide (NO) metabolism and is able to release NO from nitrosyl-hemoglobin or mitochondrial protein complexes. Therefore, the aim of this study was to evaluate and compare the therapeutic value of blue or red light emitting diodes (LEDs) on wound healing in an ischemia disturbed rodent flap model. STUDY DESIGN/MATERIALS AND METHODS: An abdominal flap was rendered ischemic by ligation of one epigastric bundle and subjected to LED illumination with a wavelength of 470 nm (blue, n = 8) or 629 nm (red, n = 8) each at 50 mW/cm(2) and compared to a non-treated control group (n = 8). Illumination was performed for 10 minutes on five consecutive days. RESULTS: LED therapy with both wavelengths significantly increased angiogenesis in the sub-epidermal layer and intramuscularly (panniculus carnosus muscle) which was associated with significantly improved tissue perfusion 7 days after the ischemic insult. Accordingly, tissue necrosis was significantly reduced and shrinkage significantly less pronounced in the LED-treated groups of both wavelengths. CONCLUSIONS: LED treatment of ischemia challenged tissue improved early wound healing by enhancing angiogenesis irrespective of the wavelength thus delineating this noninvasive means as a potential, cost effective tool in complicated wounds.

Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1α and MMP-2.

It is known that low level laser therapy is able to improve skin flap viability by increasing angiogenesis. However, the mechanism for new blood vessel formation is not completely understood. Here, we investigated the effects of 660 nm and 780 nm lasers at fluences of 30 and 40 J/cm(2) on three important mediators activated during angiogenesis. Sixty male Wistar rats were used and randomly divided into five groups with twelve animals each. Groups were distributed as follows: skin flap surgery non-irradiated group as a control; skin flap surgery irradiated with 660 nm laser at a fluence of 30 or 40 J/cm(2) and skin flap surgery irradiated with 780 nm laser at a fluence of 30 or 40 J/cm(2). The random skin flap was performed measuring 10×4 cm, with a plastic sheet interposed between the flap and the donor site. Laser irradiation was performed on 24 points covering the flap and surrounding skin immediately after the surgery and for 7 consecutive days thereafter. Tissues were collected, and the number of vessels, angiogenesis markers (vascular endothelial growth factor, VEGF and hypoxia inducible factor, HIF-1α) and a tissue remodeling marker (matrix metalloproteinase, MMP-2) were analyzed. LLLT increased an angiogenesis, HIF-1α and VEGF expression and decrease MMP-2 activity. These phenomena were dependent on the fluences, and wavelengths used. In this study we showed that LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1α expression in a dose dependent manner.

[Endovascular brachytherapy (EVBT) with Rhenium-188 for restenosis prophylaxis after angioplasty of infrainguinal lesions: early experience]. / Endovaskuläre Brachytherapie (EVBT) mit Rhenium-188 zur Restenoseprophylaxe nach Angioplastie infrainguinaler Läsionen: Erste Erfahrungen.

PURPOSE: Restenosis remains a major problem in percutaneous transluminal angioplasty (PTA) of peripheral arteries. The aim of this feasibility study was to evaluate the technical feasibility and safety of a new endovascular brachytherapy (EVBT) device with Rhenium-188 in restenosis prophylaxis of infrainguinal arteries. MATERIALS AND METHODS: From March 2006 to April 2009, 52 patients with 71 infrainguinal arterial lesions were treated with Re-188 to prevent restenosis after PTA. 40 patients with 53 lesions (24 de-novo lesions and 29 restenoses) were reexamined (clinic, color-coded duplex ultrasound) after a mean follow-up period of 12.7 months (2.6 to 25.1 months). The liquid beta-emitter Re-188 was introduced to the target lesion via an EVBT certified PTA balloon and a tungsten applicator. After the calculated irradiation time, Re-188 was aspirated back into the tungsten applicator. A dose of 13 Gy was applied at a depth of 2 mm into the vessel wall. RESULTS: After a mean follow-up of 12.7 months, the overall restenosis rate after Re-PTA was 15.1 % (8 / 53 lesions). The restenosis rate for de-novo lesions was 20.8 % (5 / 24) and 10.3 % for restenoses (3 / 29). In 4 patients reintervention was necessary (3 PTAs and 2 major amputations). No periprocedural complications were observed. No elevated radiation dose for the patient or the interventionalist was measured. CONCLUSION: EVBT with a Re-188 filled balloon catheter was technically feasible and safe after PTA of infrainguinal arterial lesions with restenosis rates lower than expected compared to published results. Treatment of restenoses seems to be more effective than de-novo lesions.

Cutaneous low-dose radiation increases tissue vascularity through upregulation of angiogenic and vasculogenic pathways.

BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally.

[Cytological study of the kidney ischemic lesions in rats].

The course of reparative regeneration after 5/6 nephrectomy and use of low-dose radiation has been studied by means of light and electron microscopy. The experiments were performed on 30 male Wistar rats. All animal procedures were conducted after approval of the protocol by the animal Studies Ethics Committee of the University of Tartu. Renal ablation was then accomplished by right nephrectomy and selective ligation of extrarenal branches of the left renal artery such that approximately 2/3 of the left kidney was infracted. All together 30 rats were randomised after the surgery and divided into two groups matched for age and body weight at week 0 and studied during 2, 4 and 8 weeks: groups I (nephrectomized, n = 15), groups II (nephrectomized and irradiated, n = 15). Left kidney of II groups rats was irradiated (60Co) 24 h after surgery in anaesthetized (Brietal) animals with 3 Gy in a single dose. As a result of experimentally induced ischemia destruction of renal corpuscles, perishing of tubular epithelial cells and and proliferation of connective tissue is followed. Reparative regeneration is based on aseptic inflammation, duration of its phases depends on the extent of organ impairment. In nephrectomized rats parallel to reparative regeneration, necrosis and deposition of calcium is found in the cortical substance. Calcium plays important role in kidney metabolism and its increased content is characteristic to degenerative changes. The experiments reveal that use of low-dose radiation does not accelerate process of reparative regeneration in rat kidney.

Experimental model for low level laser therapy on ischemic random skin flap in rats

OBJETIVO: Propor o desenvolvimento de um modelo experimental para verificar o efeito da laserterapia de baixa intensidade na viabilidade do retalho cutâneo randômico em ratos. MÉTODOS: A amostra constituiu-se de 24 ratos, da linhagem Wistar-EPM. O retalho cutâneo randômico foi realizado com dimensões de 10x4 cm e uma barreira plástica foi interposta entre o mesmo e o leito doador. O Grupo 1 (controle), foi submetido a uma simulação de tratamento com a irradiação laser de diodo (830 nm). O Grupo 2 foi submetido à irradiação laser de diodo (830 nm). Os animais foram submetidos a terapia a laser com densidade de energia de 36 J/cm2 (72 segundos) imediatamente após a operação e nos outros quatros dias subseqüentes. A caneta do laser foi posicionada a 90 graus em contato com o retalho cutâneo em um ponto a 2,5 cm da base cranial do retalho. No sétimo dia pós-operatório foram calculadas as porcentagens da área de necrose. RESULTADOS: O Grupo 1 apresentou média da área de necrose de 48,86% e o Grupo 2 – 23,14%. Após a análise estatística, os resultados mostraram que o Grupo 2 foi mais eficaz, quando comparado ao controle (p<0,001).CONCLUSÃO: O modelo experimental mostrou-se factível para estudos dos efeitos da terapia a laser de baixa intensidade em retalho cutâneo randômico em ratos.

Experimental model for low level laser therapy on ischemic random skin flap in rats.

PURPOSE: To develop an experimental model to be used in the study of low level Laser therapy on viability of random skin flap in rats. METHODS: The sample was 24 Wistar-EPM rats. The random skin flap measured 10 x 4 cm and a plastic sheet was interposed between the flap and donor site. Group 1 (control) underwent sham irradiation with diode laser (830 nm). Group 2 was submitted to laser irradiation with diode laser (830 nm). The animals were submitted to Laser therapy with 36 J/cm(2) energy density (72 seconds) immediately after the surgery and on the four subsequent days. The probe was usually held in contact with the skin flap surface on a point at 2.5 cm cranial from the flap base. On the seventh postoperative day, the percentage of necrotic area was measured and calculated. RESULTS: Group 1 reached an average necrotic area of 48.86%, Group 2 - 23.14%. After the statistic analysis, compared with the control group, Group 2 showed a statistically significant increase in survival area (p<0.001). CONCLUSION: The experimental model proved to be reliable to be used in the study of effects of low level laser therapy in random skin flap in rats.

Endovascular gamma irradiation for the prevention restenosis after angioplasty of femoropopliteal de novo stenoses.

The purpose of this study was to investigate the effectiveness and detect side effects of centered, overlapped endovascular gamma irradiation after angioplasty of de novo femoropopliteal stenoses. Thirty patients (age 65.3+/-9.2 years) with arterial occlusive disease were prospectively enrolled to receive endovascular gamma irradiation (192-iridium, 14 Gy centered at 2 mm vessel wall) immediately after percutaneous transluminal angioplasty (PTA) of femoropopliteal stenoses. Irradiation overlapped dilatation by 1-2 cm at each end. Follow-up involved angiography after 12 months; duplex sonography; and interviews before and after PTA and at 1, 6, and 12 months follow-up. PTA and centered endovascular irradiation were performed successfully in all patients. Three thromboembolic complications occurred during irradiation. Angiographic and clinical follow-up was possible in 28 patients. The angiographic degree of stenosis was 73.8%+/-16.3% before and 3.6%+/-23.5% after PTA and was 3.5%+/-43.7% at the 1-year follow-up. Restenosis (>50%) of the target lesion developed in three patients (10.7%) and edge stenoses (>30%) in nine patients (32.1%). An aneurysm of the irradiated segment in one patient was treated by stenting. The rate of retreatment was 17.9%. The vessel diameter after endovascular gamma irradiation and PTA of femoropopliteal stenoses remained stable. Restenosis, induction of edge stenoses, and aneurysm were reasons for reinterventions.

Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization.

Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell-dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)-dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9-deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sl(d) mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sl(d) mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues.

Endovascular brachytherapy: effect on acute inflammatory response after percutaneous femoropopliteal arterial interventions.

PURPOSE: To investigate whether endovascular brachytherapy diminishes vascular inflammation in response to femoropopliteal percutaneous transluminal angioplasty (PTA) or stent implantation in two double-blind randomized-controlled trials. MATERIALS AND METHODS: Forty-seven consecutive patients from two double-blind randomized-controlled trials were studied. Patients either underwent femoropopliteal PTA with endovascular gamma irradiation (n = 8) or placebo irradiation (n = 7) or underwent PTA and stent implantation with brachytherapy (n = 15) or placebo irradiation (n = 17). High-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen levels were measured at baseline and 8, 24, and 48 hours after the intervention. The change of acute phase parameters from baseline to 48 hours after intervention indicated the extent of the inflammatory response and was compared between patients undergoing brachytherapy and those undergoing placebo irradiation. Fisher exact test was used for comparison of categorical data, and nonparametric statistical methods were applied for analysis of continuous data (Mann-Whitney U tests for unpaired data and Friedman analysis for repetitive measurements). RESULTS: Median patient age was 70 years (interquartile range, 56-74 years); 33 (70%) patients were men and 14 (30%) were women. Clinical characteristics and baseline values of acute phase parameters were similar between groups. A statistically significant increase in CRP, SAA, and fibrinogen values was observed after PTA and stent implantation, both in the patients who underwent brachytherapy and in those who underwent placebo irradiation. Compared with placebo irradiation, however, brachytherapy did not significantly reduce any acute phase parameter from baseline to 8, 24, or 48 hours after the intervention (P >.05 for all comparisons). CONCLUSION: Endovascular brachytherapy did not diminish early vascular inflammation in response to PTA or stent implantation and even induced a trend toward an increased inflammatory response.

Effects of diode laser therapy on blood flow in axial pattern flaps in the rat model.

Axial pattern skin flaps are a very important reparative tool for the plastic and reconstructive surgeon in the reconstruction of tissue defects. From whatever unfortunate reason, part or all of such flaps occasionally suffers from irreversible ischaemia with loss of the flap. Infrared diode laser therapy has been shown to improve local and systemic circulation. The present study was designed to assess the effect of an 830 nm diode laser (power density, 18.5 W/cm(2), energy density 185 J/cm(2)) on the blood flow of axial pattern flaps in the rat model and their survival, compared with unirradiated controls. The flaps were raised in all animals ( n=40), and blood flow assessed with laser speckle flowmetry (LSF). In the experimental groups (3 groups, n=10 per group), the flaps were irradiated either directly over the dominant feeder vessel (iliolumbar artery), at the proximal end or at the distal end of the flap itself and blood flow assessed during irradiation. Flowmetry was performed again in all animals at 5 and 10 min postirradiation, and the flaps sutured back in position. The unirradiated controls were handled in exactly the same way, but the laser was not activated. The survival rate of the flaps was assessed on the fifth postoperative day. LSF demonstrated significant increased blood flow in the flaps at 5 and 10 min postirradiation in all experimental groups compared with the control animals. At five days postirradiation, there was significantly better survival of the flaps in all the experimental groups compared with the controls ( p<0.01), but no significant difference was seen between any of the experimental groups. We conclude that laser therapy increases the blood flow and perfusion of transferred flaps, and that this has significant effects on the survival of the flaps. One possible mechanism of modulation of the autonomic nervous system is discussed.