The impact of hyperbaric oxygen therapy on late irradiation injury in oral microcirculation.

BACKGROUND: Late side effects of radiotherapy in patients with head and neck cancer (HNCPs) result in decreased tissue vascularity, a compromised healing capacity and spontaneous breakdown of tissue. The aim of this study was to examine the in vivo effect of hyperbaric oxygen therapy (HBOT) on the microcirculation in irradiated oral tissue. METHODS: Using a handheld microscope, the effect of HBOT on oral mucosal microcirculation parameters was measured in 34 previously irradiated HNCPs prior to HBOT and at 4 weeks and 6 months posttreatment. RESULTS: A significant increase in mean buccal vessel density and decrease in buccal vessel diameter was found 6 months after HBOT compared to baseline, 22 ± 11 versus 25 ± 7 cpll/mm2 (p < 0.05) and 20 ± 4 versus 16 ± 5 µm (p < 0.05), respectively. CONCLUSION: Our results indicate that oral microcirculation histopathology associated with irradiation is able to respond to HBOT by redirecting oral microcirculation parameters towards values consistent with healthy tissue.

Ultrasound-Mediated Microbubble Cavitation Transiently Reverses Acute Hindlimb Tissue Ischemia through Augmentation of Microcirculation Perfusion via the eNOS/NO Pathway.

Ultrasound-mediated microbubble cavitation improves perfusion in chronic limb and myocardial ischemia. The purpose of this study was to determine the effects of ultrasound-mediated microbubble cavitation in acute limb ischemia and investigate the mechanism of action. The animal with acute hindlimb ischemia was established using male Sprague-Dawley rats. The rats were randomly divided into three groups: intermittent high-mechanical-index ultrasound pulses combined with microbubbles (ultrasound [US] + MB group), US alone (US group) and MB alone (MB group). Both hindlimbs were treated for 10 min. Contrast ultrasound perfusion imaging of both hindlimbs was performed immediately and 5, 10, 15, 20 and 25 min after treatment. The role of the nitric oxide (NO) pathway in increasing blood flow in acutely ischemic tissue was evaluated by inhibiting endothelial nitric oxide synthase (eNOS) with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). In the US + MB group, microvascular blood volume and microvascular blood flow of the ischemic hindlimb were significantly increased after treatment (both p values <0.05), while the microvascular flux rate (ß) increased, but not significantly (p > 0.05). The increases were observed immediately after treatment, and had dissipated by 25 min. Changes in the US and MB groups were minimal. Inhibitory studies indicated cavitation increased phospho-eNOS concentration in ischemic hindlimb muscle tissue, and the increase was significantly inhibited by L-NAME (p < 0.05). Ultrasound-mediated microbubble cavitation transiently increases local perfusion in acutely ischemic tissue, mainly by improving microcirculatory perfusion. The eNOS/NO signaling pathway appears to be an important mediator of the effect.

In silico model of the early effects of radiation therapy on the microcirculation and the surrounding tissues.

BACKGROUND: Radiation-induced organ dysfunction are frequently described by Normal Tissue Complication Probability models. The approximations of this radiobiological approach do not allow to consider the important role played by the microvasculature not only in the dose-response of the blood vessels but also of the organs where it is located. To this purpose, we presented a computational model that describes the fluid dynamics of microcirculation when the parameters of the network and the surrounding tissues are affected by radio-induced changes. MATERIALS AND METHODS: The effects of the ionizing radiation on the capillary bed are mediated by the inflammatory response. We derived from a literature search the possible morphological and functional variations of the network due to the process of the acute inflammation. Specifically, we considered vasodilation, increased membrane permeability with consequent fluid extravasation and increased wall elasticity. These perturbations to the system were included in a computational model, already able to describe the physics of the microcirculation and its exchanges with the surrounding tissues. RESULTS: Two computational descriptions were considered. In the first one, we changed a set of 4 parameters associated with the increased fluid exchange from the health scenario at the baseline to a seriously compromised scenario with the edema formation. The second study investigated the effect of a perturbation to the vessel wall elasticity. CONCLUSIONS: These simulations represent a first step towards the challenging objective of understanding and describing in a mechanistic way the effects of radiation on the vascular microenvironment.

Adjunctive mesenchymal stem/stromal cells augment microvascular function in poststenotic kidneys treated with low-energy shockwave therapy.

Effective therapeutic strategies are needed to preserve renal function in patients with atherosclerotic renal artery stenosis (ARAS). Low-energy shockwave therapy (SW) and adipose tissue-derived mesenchymal stem/stromal cells (MSCs) both stimulate angiogenesis repair of stenotic kidney injury. This study tested the hypothesis that intrarenal delivery of adipose tissue-derived MSCs would enhance the capability of SW to preserve stenotic kidney function and structure. Twenty-two pigs were studied after 16 weeks of ARAS, ARAS treated with a SW regimen (bi-weekly for 3 weeks) with or without subsequent intrarenal delivery of adipose tissue-derived MSCs and controls. Four weeks after treatment, single-kidney renal blood flow (RBF) before and after infusion of acetylcholine, glomerular filtration rate (GFR), and oxygenation were assessed in vivo and the renal microcirculation, fibrosis, and oxidative stress ex vivo. Mean arterial pressure remained higher in ARAS, ARAS + SW, and ARAS + SW + MSC compared with normal. Both SW and SW + MSC similarly elevated the decreased stenotic kidney GFR and RBF observed in ARAS to normal levels. Yet, SW + MSC significantly improved RBF response to acetylcholine in ARAS, and attenuated capillary loss and oxidative stress more than SW alone. Density of larger microvessels was similarly increased by both interventions. Therefore, although significant changes in functional outcomes were not observed in a short period of time, adjunct MSCs enhanced pro-angiogenic effect of SW to improve renal microvascular outcomes, suggesting this as an effective stratege for long-term management of renovascular disease.

Evaluating the Far-Infrared Radiation Bioeffects on Micro Vascular Dysfunction, Nervous System, and Plantar Pressure in Diabetes Mellitus.

The most frequent clinical complication is diabetes. Diabetes is characterized by elevated blood glucose levels resulting in sensory nerve damage or lesions. Diabetic foot wounds are often slow to heal and require medical attention and monitoring. This study evaluates the effect of far-infrared radiation on the microcirculation and plantar pressure in the diabetic foot. Ten diabetics and 4 nondiabetics were recruited in this study. The diabetic group was examined before and after the intervention in each month for 3 consecutive months. Four nondiabetic groups were also measured before and after the intervention for 2 weeks in each month. The surface temperature and blood flow in the diabetic foot was significantly improved (temperature: 32.1 ± 2.3°C vs 33.5 ± 2.2°C, P < .05; blood flow image: 118.3 ± 58.1 PU [perfusion unit] vs 50.4 ± 4.3 PU, P < .05). The sympathetic nerve activity index LF also increased from 40.8 ± 18.6% to 61.8 ± 13.5% (P = .07) in the second month. Plantar pressure tended to increase in the third month. This might indicate that far-infrared radiation could affect the mechanical properties of the plantar foot soft tissue. These results indicated that the effects of far-infrared radiation would improve blood circulation and change the soft tissue properties in the diabetic foot.

Microvascular Effects of Pulsed Dye Laser in Combination With Oxymetazoline.

BACKGROUND AND OBJECTIVE: Oxymetazoline, an α-1A agonist, is approved by the United States Food and Drug Administration (FDA) for treatment of persistent facial erythema associated with rosacea and induces vasoconstriction by interacting with α receptors. The objective of our study was to study the microvascular effects of oxymetazoline and pulsed dye laser (PDL). MATERIALS AND METHODS: A dorsal window chamber was surgically installed on 20 mice. Each animal was assigned to one of four experimental groups: saline alone, oxymetazoline alone (10 µl applied once daily × 7 days), saline + PDL (saline applied 5 minutes before PDL irradiation [10 mm spot, 1.5 ms pulse duration, 7 J/cm2 delivered to epidermis]), or oxymetazoline + PDL (10 µl oxymetazoline applied 5 minutes before PDL and then once daily × 7 days). Brightfield and laser speckle imaging were performed for 7 days to monitor vascular architectural and functional changes. RESULTS: We observed persistent blood flow in all of the saline-only and oxymetazoline-only experiments. A higher rate of vascular shutdown was observed with oxymetazoline + PDL (66.7%) compared with saline + PDL alone (16.7%). Oxymetazoline application increased venule diameter at 5 minutes post-application and decreased both arteriole and venule diameters at 60 minutes post-application. CONCLUSION: The combination protocol of oxymetazoline + PDL induces persistent vascular shutdown observed 7 days after irradiation. This result may be associated with the acute vascular effects of oxymetazoline. Oxymetazoline + PDL should be evaluated as a treatment for cutaneous vascular disease, including rosacea and port wine birthmarks. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Besides Photothermal Effects, Low-Level CO2 Laser Irradiation Can Potentiate Skin Microcirculation Through Photobiomodulation Mechanisms.

Background: Improvement of microcirculation is one of the important mechanisms of low-level laser therapy (LLLT) to treat some diseases such as wound healing. Most previous studies have been carried out with multiple lasers other than the 10,600-nm CO2 laser. Recently, the CO2 laser has been used not only as a tool for excision of soft tissues but also for therapeutic applications. Objective: To study whether low-level CO2 laser irradiation can influence microcirculation and further explore the underlying mechanisms. Methods: Seventy-milliwatt (70-mW) CO2 lasers irradiated the forearms of 12 participants and skin blood perfusion (SkBP) was measured with a laser speckle imager. The thermal effect of irradiation was evaluated by measuring the irradiated skin in vivo and the exposed cell suspensions in vitro. Extracellular adenosine triphosphate (eATP) of the human mast cell line (HMC-1) is assessed by luciferin-luciferase assay to explore the potential mechanisms. Results: Irradiation caused dose-dependent increase in SkBP. At a medium dose of 262 J/cm2, SkBP reached its maximum value at 195.8% ± 18.6% of the baseline (n = 12, p < 0.01). Such laser irradiation had a mild thermal effect, heating local skin temperature (SkT) by 6.1°C ± 0.3°C (n = 10) and warming cell suspensions by 4.5°C ± 0.8°C (n = 6). Irradiation dose-dependently lowered eATP levels of HMC-1 cells in vitro. At a medium dose of 262 J/cm2, eATP levels declined to the minimum at 74.8% ± 5.5% of the baseline (n = 12, p < 0.01). This downregulation effect could be significantly inhibited by 100-µM ARL67156, a nonspecific ecto-ATPase inhibitor. On the contrary, heating itself slightly raised the level of eATP. Conclusions: Low-level CO2 laser irradiation can improve microcirculation. Besides the thermal effect, regulation of extravascular eATP by the photobiomodulation mechanism may be involved. This implies that CO2 lasers might be used in LLLT.

[Effects of high-dose irradiation on vascularization: Physiopathology and clinical consequences]. / Effets de l'irradiation à haute dose sur la vascularisation : physiopathologie et conséquences cliniques.

A review of the literature has been conducted to better understand the effect of stereotactic radiotherapy on tumour vascularization and their consequences. High irradiation doses cause the death of endothelial cells by apoptosis through the ceramide pathway. Vascular consequences are multiple: increased permeability, decreased blood flow, increased hypoxia and tumoral necrosis. This necrosis causes an indirect death of the cancer cells in the days following the irradiation. The importance of indirect cell death in tumour control remains controversial, but it can explain the good clinical results of stereotactic radiotherapy. Stereotactic radiotherapy is a treatment of the tumour microenvironment. Tumour recurrence in this hypoxic environment is slower through disturbance of revascularization mechanisms but also more aggressive, with increased resistance to treatment and a higher risk of metastasis. In a longer time, vascular damage leads to chronic inflammation and a dysfunctional healing process resulting in vascular occlusion. This phenomenon is used in the treatment of arteriovenous malformations but is also responsible for damage to healthy tissues responsible for chronic complications. This is why high-dose irradiation can only be delivered using stereotactic radiotherapy, which reduces the irradiated volume.

Preclinical quantitative in-vivo assessment of skin tissue vascularity in radiation-induced fibrosis with optical coherence tomography.

Radiation therapy (RT) is widely and effectively used for cancer treatment but can also cause deleterious side effects, such as a late-toxicity complication called radiation-induced fibrosis (RIF). Accurate diagnosis of RIF requires analysis of histological sections to assess extracellular matrix infiltration. This is invasive, prone to sampling limitations, and thus rarely used; instead, current practice relies on subjective clinical surrogates, including visual observation, palpation, and patient symptomatology questionnaires. This preclinical study demonstrates that functional optical coherence tomography (OCT) is a useful tool for objective noninvasive in-vivo assessment and quantification of fibrosis-associated microvascular changes in tissue. Data were collected from murine hind limbs 6 months after 40-Gy single-dose irradiation and compared with nonirradiated contralateral tissues of the same animals. OCT-derived vascular density and average vessel diameter metrics were compared to quantitative vascular analysis of stained histological slides. Results indicate that RIF manifests significant microvascular changes at this time point posttreatment. Abnormal microvascular changes visualized by OCT in this preclinical setting suggest the potential of this label-free high-resolution noninvasive functional imaging methodology for RIF diagnosis and assessment in the context of clinical RT.

Peculiar Effects of Electromagnetic Millimeter Waves on Tumor Development in BALB/c Mice.

The study examined the effects of millimeter electromagnetic waves at a frequency of 130 GHz corresponding to the molecular absorption and radiation spectra of NO and O2 with the total exposition time of 6 h on tumor morphogenesis in 3- and 6-month-old tumor-prone BALB/c mice of both sexes. In experimental mice exposed to electromagnetic radiation, the development of cancer process was slowed down throughout the observation period; moreover, no macroscopic signs of the tumors were revealed. However, in contrast to control mice, experimental animals demonstrated the formation of pathological reactions reflected by hepatic biochemical indices accompanied by the development of dystrophic and microcirculatory alterations in the liver tissue.

Patient-Side Appraisal of Late Radiation-Induced Oral Microvascular Changes.

PURPOSE: To determine the clinical feasibility of examining and measuring late irradiation changes in the oral microcirculation of head and neck (HN) cancer patients using the novel CytoCam video microscope system. METHODS AND MATERIALS: In 30 HN cancer patients and 30 age-matched controls, bilateral video images were recorded noninvasively of the oral microcirculation of the buccal mucosa and mandibular gingiva. Tissue perfusion parameters, such as functional capillary density (FCD), buccal blood vessel diameter, and microcirculatory flow index, were analyzed. RESULTS: No difference was observed for mean buccal mucosa FCD in irradiated versus healthy tissue, whereas a lower mean gingival FCD in irradiated versus healthy tissue was observed (34 ± 17 capillaries per millimeter squared [cpll/mm2] vs 68 ± 19 cpll/mm2; P < .001). A significant difference in mean buccal blood vessel diameter of 16 ± 3 µm was measured, compared with 14 ± 1 µm in control buccal mucosa (P < .001). No significant difference in microcirculatory flow index was observed between the 2 groups. CONCLUSIONS: Quantifying oral microcirculatory injury associated with late irradiation effects using the CytoCam was feasible in HN cancer patients. Results indicate that marked differences in tissue-specific microcirculatory measurements of angioarchitecture, diminished capillary density, and extensively dilated blood vessel diameters are associated with late irradiation effects in HN cancer patients.

Correlation between Flicker-Induced Retinal Vessel Vasodilatation and Plasma Biomarkers of Endothelial Dysfunction in Hypertensive Patients.

PURPOSE: Hypertension (HT) strongly affects the vascular endothelium, resulting in chronic inflammatory disease. Dynamic vessel analysis (DVA) is a modern methodological approach to analyze vascular function in the retinal microcirculation. The aim of this study was to examine whether a defective retinal vessels response is associated with HT-induced endothelial dysfunction. MATERIALS AND METHODS: Retinal vessel reactions to flicker stimulation were examined by DVA in both eyes of 37 hypertensive and 41 healthy control subjects. Plasma concentrations of C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNFɑ) were measured using the enzyme-linked immunosorbent assay. RESULTS: Both arterial and vein responses to flicker stimulation were significantly decreased in patients with HT compared with the healthy controls (dilatation of the arteries was lower in the HT group by, on average, 1.31, p = 0.001 and dilatation of the veins was lower in the HT group by, on average, 1.32, p = 0.002) after independent adjustment for age, sex, body mass index, and pressure values. In the hypertensive group, there was a negative correlation between the arterial response to flicker stimulation and the plasma CRP concentration (Spearman's Rank-order Coefficient (Rs) = -0.29, p = 0.07). Similarly, the plasma TNFα concentrations negatively correlated with the arterial response to flicker stimulation (Rs = -0.39, p = 0.02). CONCLUSIONS: Our results indicate that DVA directly reflects the actual metabolic status of the retinal endothelium. DVA might be used as an early noninvasive screening tool to detect vascular dysregulation and pan-endothelial dysfunction in patients with HT.

In-vivo longitudinal imaging of microvascular changes in irradiated oral mucosa of radiotherapy cancer patients using optical coherence tomography.

Mucositis is the limiting toxicity of radio(chemo)therapy of head and neck cancer. Diagnostics, prophylaxis and correction of this condition demand new accurate and objective approaches. Here we report on an in vivo longitudinal monitoring of the oral mucosa dynamics in 25 patients during the course of radiotherapy of oropharyngeal and nasopharyngeal cancer using multifunctional optical coherence tomography (OCT). A spectral domain OCT system with a specially-designed oral imaging probe was used. Microvasculature visualization was based on temporal speckle variations of the full complex signal evaluated by high-pass filtering of 3D data along the slow scan axis. Angiographic image quantification demonstrated an increase of the vascular density and total length of capillary-like-vessels before visual signs or clinical symptoms of mucositis occur. Especially significant microvascular changes compared to their initial levels occurred when grade two and three mucositis developed. Further, microvascular reaction was seen to be dose-level dependent. OCT monitoring in radiotherapy offers a non-invasive, convenient, label-free quantifiable structural and functional volumetric imaging method suitable for longitudinal human patient studies, furnishing fundamental radiobiological insights and potentially providing useful feedback data to enable adaptive radiotherapy (ART).

[The application of low-frequency ultrasound for the comprehensive treatment and rehabilitation of the patients presenting with chronic endometritis]. / Primenenie nizkochastotnogo ul'trazvuka v kompleksnoi terapii i reabilitatsii patsientok s khronicheskim éndometritom.

The incidence of chronic endometritis remains rather high despite considerable progress in reproductive medicine including the advent of the new methods for assisted reproduction; the pregnancy rate after the treatment of this condition is still unacceptably low. It implies the necessity of the careful preparation of endometrium for the implantation of the embryo especially in women with a history of unsuccessful outcomes of the IVF treatment. It calls for the development of the efficient therapeutic modalities for the management of chronic endometritis and restoration of the normal reproductive function; their introduction into the therapeutic algorithm remains equally relevant. The characteristic features of chronic endometritis include blood circulatory disorders in the vessels of the uterus and in the pelvic vascular basin, changes of local immunity in the endometrium concomitant with the activation of cellular and humoral responses of inflammation in the form of enhanced leukocyte infiltration and increased production of cytokines. The long duration of such a process results in the development of fibrosis that, in its turn, leads to chronic tissue hypoxia, potentiation of inflammation, and disruption of decidualization that hampers successful implantation. The article shows the possibility of using low-intensity ultrasound for the treatment and rehabilitation of the patients presenting with chronic endometritis. The data concerning the primary biophysical processes developing in the tissues under the influence of ultrasound are discussed. The therapeutic effects and their underlying mechanisms and described. The physiotherapeutic treatment considerably improved vascular hemodynamics in the pelvic basin and produced trophotropic, defibrosing, and anti-inflammatory effects. The clinical data giving evidence of the high effectiveness of the application of intrauterine ultrasound cavitation provide a basis for the recommendation to include this physical factor in the existing algorithms for the pre-gravid preparation of the women presenting with disorders of the reproductive function and chronic endometritis.

The effect of LED on blood microcirculation during chronic wound healing in diabetic and non-diabetic patients-a prospective, double-blind randomized study.

Chronic wounds, especially in diabetic patients, represent a challenging health issue. Since standard treatment protocols often do not provide satisfactory results, additional treatment methods-like phototherapy using low-level light therapy-are being investigated. The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients. Since a sufficient blood supply is mandatory for wound healing, the evaluation of microcirculation in the healthy skin at a wound's edge was the main outcome measure. Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were randomized to the treated and control groups. The treated group received phototherapy with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks, and the control group received phototherapy with broadband 580-900 nm and power density 0.72 J/cm2. Microcirculation was measured using laser Doppler. A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients (p = 0.040 and p = 0.033), while there was no difference in the control groups. Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group. According to our results, phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients.

Flow Induced Microvascular Network Formation of Therapeutic Relevant Arteriovenous (AV) Loop-Based Constructs in Response to Ionizing Radiation.

BACKGROUND The arteriovenous (AV) loop model enables axial vascularization to gain a functional microcirculatory system in tissue engineering constructs in vivo. These constructs might replace surgical flaps for the treatment of complex wounds in the future. Today, free flaps are often exposed to high-dose radiation after defect coverage, according to guideline-oriented treatment plans. Vascular response of AV loop-based constructs has not been evaluated after radiation, although it is of particular importance. It is further unclear whether the interposed venous AV loop graft is crucial for the induction of angiogenesis. MATERIAL AND METHODS We exposed the grafted vein to a single radiation dose of 2 Gy prior to loop construction to alter intrinsic and angio-inductive properties specifically within the graft. Vessel loops were embedded in a fibrin-filled chamber for 15 days and radiation-induced effects on flow-mediated vascularization were assessed by micro-CT and two-dimensional histological analysis. RESULTS Vessel amount was significantly impaired when an irradiated vein graft was used for AV loop construction. However, vessel growth and differentiation were still present. In contrast to vessel density, which was homogeneously diminished in constructs containing irradiated veins, vessel diameter was primarily decreased in the more peripheral regions. CONCLUSIONS Vascular luminal sprouts were significantly diminished in irradiated venous grafts, suggesting that the interposing vein constitutes a vital part of the AV loop model and is essential to initiate flow-mediate angiogenesis. These results add to the current understanding of AV loop-based neovascularization and suggest clinical implications for patients requiring combined AV loop-based tissue transfer and adjuvant radiotherapy.

Intraglandular Transplantation of Adipose-Derived Stem Cells for the Alleviation of Irradiation-Induced Parotid Gland Damage in Miniature Pigs.

PURPOSE: In a previous study, the authors verified the protective efficacy of adipose-derived stem cells (ADSCs) on the prevention of salivary gland (SG) damage induced by irradiation in mice. As a critical step before implementation in clinical practice, the present study investigated the protective effect of ADSCs in a miniature pig SG model, because miniature pigs share many characteristics with humans. MATERIALS AND METHODS: Third-passage autologous ADSCs at a concentration of 4 × 106 cells/mL were transplanted by intraglandular injection into parotid glands (PGs) immediately after local irradiation at a single dose of 20 Gy. The injection process was repeated twice a week for 6 consecutive weeks. At 12 weeks after irradiation, functional and histologic evaluations were performed by measuring salivary flow rate (SFR) and hematoxylin and eosin and periodic acid-Schiff staining. Immunohistochemical and transmission electron microscopic examinations also were conducted to evaluate amylase (AMY) production, microvessel density (MVD), and microstructural changes. RESULTS: The irradiated PGs showed remarkable decreases in SFR, AMY production, and MVD. However, transplantation of ADSCs alleviated irradiated PG morphology and function by preserving more functional acinar cells and increasing SFR and AMY production. In addition, greater MVD was observed in the ADSC-treated group than in the irradiated group. CONCLUSIONS: These results indicated that intraglandular transplantation of autologous ADSCs is an effective method to protect PGs against damage from irradiation in miniature pigs, which might have clinic application in the future.

Evaluation of acute skin toxicity in breast radiotherapy with a new quantitative approach.

BACKGROUND AND PURPOSE: Current criteria to evaluate acute radiodermatitis are highly subjective so quantification of physiological parameters is needed. We describe a non-invasive method of assessing skin microcirculation in breast cancer patients treated with hypofractionated radiotherapy and correlate them with the CTCAE scale. METHODS: Prospective study of 63 patients where blood flow was measured with real-time laser Doppler flowmetry (LDF) at baseline, weekly, and 3-months post-radiotherapy. Skin toxicity was assessed with the microcirculation index (MCI), a novel index based on blood flow parameters obtained via LDF. RESULTS: MCI was positively correlated (R=0.647; p<0.001) with the dose. Changes in MCI from baseline to the end of radiotherapy and at 3-months post-radiotherapy were significant (p<0.001). All CTCAE groups experienced a significant increase in MCI values from baseline to end of radiotherapy (p<0.001 for CTCAE grades 0 and 1; and p=0.028 for the grade 2 group). Significant differences in MCI values were observed among CTCAE groups at the end of radiotherapy (p=0.016). CONCLUSIONS: LDF is an accurate and objective measure of changes in blood flow. The comparison with the CTCAE shows the limitations of this subjective way of classifying patients. LDF is the first step for future studies of radiodermatitis treatments and prevention.

Effect of Prewarming during Induction of Anesthesia on Microvascular Reactivity in Patients Undergoing Off-Pump Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

BACKGROUND: General anesthesia may induce inadvertent hypothermia and this may be related to perioperative cardiovascular complications. Microvascular reactivity, measured by the recovery slope during a vascular occlusion test, is decreased during surgery and is also related to postoperative clinical outcomes. We hypothesized that microvascular changes during surgery may be related to intraoperative hypothermia. To evaluate this, we conducted a randomized study in patients undergoing off-pump coronary artery bypass surgery, in which the effect of prewarming on microvascular reactivity was evaluated. METHODS: Patients scheduled for off-pump coronary artery bypass surgery were screened. Enrolled patients were randomized to the prewarming group to receive forced-air warming during induction of anesthesia or to the control group. Measurement of core and skin temperatures and vascular occlusion test were conducted before anesthesia induction, 1, 2, and 3 h after induction, and at the end of surgery. RESULTS: In total, 40 patients were enrolled and finished the study (n = 20 in the prewarming group and n = 20 in the control group). During the first 3 h of anesthesia, core temperature was higher in the prewarming group than the control group (p < 0.001). The number of patients developing hypothermia was lower in the prewarming group than the control group (4/20 vs. 13/20, p = 0.004). However, tissue oxygen saturation and changes in recovery slope following a vascular occlusion test at 3 h after anesthesia induction did not differ between the groups. There was no difference in clinical outcome, including perioperative transfusion, wound infection, or hospital stay, between the groups. CONCLUSIONS: Prewarming during induction of anesthesia decreased intraoperative hypothermia, but did not reduce the deterioration in microvascular reactivity in patients undergoing off-pump coronary artery bypass surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02186210.

Effects of pulsed electromagnetic fields on peripheral blood circulation in people with diabetes: A randomized controlled trial.

Cutaneous blood flow provides nourishment that plays an essential role in maintaining skin health. We examined the effects of pulsed electromagnetic fields (PEMFs) on cutaneous circulation of dorsal feet. Twenty-two patients with diabetes mellitus (DM) and 21 healthy control subjects were randomly allocated to receive either PEMFs or sham PEMFs (0.5 mT, 12 Hz, 30 min). Blood flow velocity and diameter of the small vein were examined by using ultrasound biomicroscopy; also, microcirculation at skin over the base of the 1st metatarsal bone (Flux1) and distal 1st phalange (Flux2) was measured by laser Doppler flowmetry before and after intervention. Results indicated that PEMFs produced significantly greater changes in blood flow velocity of the smallest observable vein than did sham PEMFs (both P < 0.05) in both types of subjects. However, no significant difference was found in changes of vein diameter, nor in Flux1 and Flux2, between PEMFs and sham PEMFs groups in subjects with or without DM. We hypothesized that PEMFs would increase blood flow velocity of the smallest observable vein in people with or without DM. Bioelectromagnetics. 37:290-297, 2016. © 2016 Wiley Periodicals, Inc.