Laser Doppler Flow Research Articles

Effect of paeoniflorin on distal survival of random flaps

BackgroundDistal ischemic necrosisis a common complication of orthopedic random skin flaps surgery. Paeoniflorin, a natural compound extracted from Paeonia lactiflora, can enhances angiogenesis and alleviates excessive inflammatory response. We investigated the changes of ischemic extra-long flaps with paeoniflorin and its possible mechanism. MethodsWe raised dorsal McFarlane flaps in 54 Sprague-Dawley rats. We designed three groups of rats: high-paeoniflorin group (HP, 50 mg/kg/d), low-paeoniflorin group (LP, 20 mg/kg/d), and control group. The flap survival rate was calculated, seven days after flap construction.Blood perfusion was detected by laser Doppler flow imaging, and angiogenesis wasdetected by Lead oxide/gelatin angiography.Oxidative stress levels of flaps were determined by detecting superoxide dismutase (SOD) and malondialdehyde (MDA). The histopathological status of flap was evaluated by hematoxylin and eosin (H&E) staining.Immunohistochemistry was used to determine the expression of high mobility group protein B1 (HMGB1), nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-18, vascular endothelial growth factor (VEGF), cysteine protease-1 (caspase-1) and NLPR3. ResultsThe flap survival rates and SOD activity in the experimental groups were significantly higher, while MDA activity was lower. Experimental groups showed significantly improved microcirculatory blood flow to the flap and increased angiogenesis. Immunohistochemistry revealed that paeoniflorin was associated with significantly increased VEGF expression, and decreased level of HMGB1, TLR4, TNF-α, NF-κB, IL-6, IL-1β, caspase-1, NLPR3, and IL-18. ConclusionsPaeoniflorin effectively enhanced the survival of rat random skin flaps by promoting vascular hyperplasia, inhibiting pyroptosis, and down-regulating inflammation.

Non-thermal Infrared Light Treatment of Ischemia/Reperfusion Injury and Subsequent Analysis of Macrophage Differentiation.

Tissue damage and necrosis from inflammatory processes are a consequence of ischemia reperfusion injury (IRI). In skeletal muscle, ischemia reduces the aerobic energy capacity of muscle cells, leading to adverse biochemical alterations and inflammation. The goal of this study is to show that exposure to near-infrared light (NIR) during a period of ischemia reduces IRI by decreasing necrosis and inflammation in addition to decreasing proinflammatory M1 and increasing protective M2 macrophages. C57/Bl6 mice underwent unilateral tourniquet-induced hindlimb ischemia for 3 h followed by reperfusion for either 15 or 30 min. Mice were randomly assigned to 3 groups. Group 1 underwent IRI with 30 min reperfusion. Group 2 underwent IRI with a 15 min reperfusion. Each group consisted of 50% no-NIR and 50% NIR-treated mice with exposure of 50 mW/cm2 for 5 min/1 h after tourniquet closure. Group 3 were sham animals anesthetized for 3 h omitting IRI. Laser doppler flow imaging was performed on all mice to confirm ischemia and reperfusion. Flow data were expressed as the ratio of ischemic limb and the contralateral control. The mice were euthanized after reperfusion, and the quadriceps and gastrocnemius were harvested. Immunoprecipitation and western blot of macrophage-markers CD68 (M1) and CD206 (M2) were performed and normalized to CD14 expression. The expression of the inflammatory markers CXCL1 and CXCL5 was significantly reduced by NIR in the IRI group. A significant decrease in CD68 and an increase in CD206 expression was observed in animals receiving IR and NIR. Tissue necrosis was decreased by NIR in the IRI group, as visualized by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The findings demonstrate that exposure to NIR reduced IRI and improved tissue survival. NIR reduced inflammation, decreased proinflammatory M1, and increased protective M2 macrophages. Exposure to NIR reduced inflammation and enhanced regeneration, leading to tissue protection following ischemia.

Relationship of Laser-Doppler-Flow and coronary perfusion and a concise update on the importance of coronary microcirculation in donor heart machine perfusion.

Machine perfusion (MP) is a novel method for donor heart preservation. The coronary microvascular function is important for the transplantation outcome. However, current research on MP in heart transplantation focuses mainly on contractile function. We aim to present the application of Laser-Doppler-Flowmetry to investigate coronary microvascular function during MP. Furthermore, we will discuss the importance of microcirculation monitoring for perfusion-associated studies in HTx research. Porcine hearts were cardioplegically arrested and harvested (Control group, N = 4). In an ischemia group (N = 5), we induced global ischemia of the animal by the termination of mechanical ventilation before harvesting. All hearts were mounted on an MP system for blood perfusion. After 90 minutes, we evaluated the effect of coronary perfusion pressures from 20 to 100 mmHg while coronary laser-doppler-flow (LDF) was measured. Ischemic hearts showed a significantly decreased relative LDF compared to control hearts (1.07±0.06 vs. 1.47±0.15; p = 0.034). In the control group, the coronary flow was significantly lower at 100 mmHg of perfusion pressure than in the ischemia group (895±66 ml vs. 1112±32 ml; p = 0.016). Laser-Doppler-Flowmetry is able to reveal coronary microvascular dysfunction during machine perfusion of hearts and is therefore of substantial interest for perfusion-associated research in heart transplantation.

Laser-Doppler microvascular flow of dental pulp in relation to caries progression

Pulpal blood supply can be measured noninvasively and objectively via laser-Doppler fluxmetry. The aim of the study was to measure and compare pulpal laser-Doppler (LD) flux values for permanent non-carious teeth and carious teeth with different degrees of caries progression. Conventional sensitivity tests were also conducted for a comparative analysis to clarify the difference between tooth sensitivity and vitality. Carious lesions were detected and assessed in 15 adult subjects using the International Caries Detection and Assessment System (ICDAS) criteria. Pulpal sensitivity of selected carious teeth (without previous prosthetic restoration or endodontic treatment) and suitable caries-free teeth were then tested with a cold stimulus and subsequently with a weak electric current, whereas their pulpal LD flux was recorded at a separate visit using individually designed silicone probe holders. The LD flux values for teeth with an ICDAS score 6 were significantly lower compared to the values for teeth with an ICDAS score 1 (p < 0.05). Pulpal LD flux values of teeth with active caries were significantly lower than those of teeth with solely inactive carious lesions (p < 0.05). The degree of agreement between sensitivity and vitality testing was fair within both of the pairs: cold test/LDF (κk = 0.232, p = 0.00) and electric test/LDF (κk = 0.354, p = 0.00). Pulpal LD flux measurement proved to be reliable in the pulp vitality assessment of carious and non-carious teeth and might improve the reliability of clinical decisions when used in addition to standard clinical diagnostic protocols.

CT-Guided Placement of a Neuromonitoring Suite in Swine for Trauma and Resuscitation Research

Background: This manuscript aims to describe a standardized method for placement of a neuromonitoring suite into the brain of a porcine model using CT guidance for use in trauma and resuscitation research.&#x0D; Methods: A baseline CT allowed for precise planning of the placement of the neuromonitoring suite including measurement of skull thickness at the location of the intended burr hole. After the burr hole was drilled, three neuromonitoring probes (pressure catheter, temperature probe, and laser doppler flow probe) were advanced into the brain parenchyma of the swine. A subsequent CT confirmed appropriate placement of the neuromonitoring suite.&#x0D; Results: Effective placement of the neuromonitoring suite was accomplished successfully and without complication in 6 Yorkshire swine. Mean duration of the procedure was 49.6 minutes ± 6.3. Representative data from one animal includes the following presented as mean ± standard deviation: intracranial pressure of 10 ± 0 mmHg, cerebral perfusion pressure of 61 ± 1 mmHg, intracranial temperature of 34.8 ± 0 °C, and brain perfusion of 704 ± 13 relative perfusion units.&#x0D; Conclusions: This CT-guided method facilitates placement of a neuromonitoring suite in a safe and reliable manner. The use of a neuromonitoring suite using CT may offer valuable insight into cerebral perfusion in the context of endovascular resuscitation.

Study Protocol: A 2-Month Cross-Over Controlled Feeding Trial Investigating the Effect of Animal and Plant Protein Intake on the Metabolome and Cardiometabolic Health

ObjectivesA dietary shift in favor of plant protein (PP) sources over animal protein (AP) sources has been advocated for both sustainability and health reasons, this dietary transition being noticeably associated to decreased cardiovascular and diabetes risks. The differences in amino acid composition between PP and AP may have several effects on the metabolic pathways, and in turn health impacts, which are still poorly characterized. This project aims at characterizing, with a combination of “omics” approaches, the metabolic reorientations induced by a dietary shift from AP to PP sources and understanding their health effects in a population at cardiometabolic risk. MethodsWe will conduct a cross-over randomized feeding trial (NCT04236518) in 20 healthy overweight males (BMI 25–35), aged 25–55, with an enlarged waist circumference (> 94cm) and high plasma triglycerides (>1.5g/L). Participants will be assigned for 1 month each to 2 diets containing predominantly either AP (65% AP:35% PP) or PP (35% AP:65% PP) in a randomized order, separated by a 2-week wash-out period. Lunch and diner will be directly provided while dietary guidelines will be given for breakfast and snacks. Blood, urine and stool samples will be collected at the fasted state every 2 weeks. At the end of each dietary intervention, blood and urine will be collected following a high fat meal, which challenges metabolism and vascular homeostasis. Plasma and urine non-targeted metabolomics analyses (LC-MS) will be combined with Peripheral Blood Mononuclear Cell (PBMC) transcriptomics and fluxomics analyses (D2O tracer) to get a comprehensive overview of the metabolic phenotype associated with AP or PP intake. Flow-Mediated Dilatation (FMD) and Flow Laser Doppler (FLD) will be used to measure respectively macrovascular endothelial function and microvascular skin blood flow at the fasted state and after the high-fat meal. We will also measure anthropometric parameters and analyze biochemistry and inflammatory markers. ResultsNot applicable (protocols abstract). ConclusionsWe expect the multi-omics fingerprinting to reveal subtle metabolic differences associated to AP or PP intake, with a positive effect of PP intake. Improved inflammatory status and endothelial function are also expected to be associated to PP intake. Funding SourcesINRAE and Roquette Frères.

Prognostic markers of post-traumatic dental external root resorption in children-a pilot study.

External inflammatory root resorption (EIRR) is a frequent complication of traumatic dental injuries (TDI). The aim of this cohort study was to identify novel non-invasive markers of post-traumatic EIRR by assessing the changes in the pulp's blood flow and the composition of gingival sulcus fluid (GCF) in children after dental trauma. Thirty-two children were enrolled and assessed within 48h of a TDI to their permanent incisors and during an additional three visits over a 6-months follow up period. During each visit, a radiograph and laser Doppler flow (LDF) measurements of the pulp blood flow were performed on the injured tooth, and the GCF was sampled. The permanent first molar tooth of the same subject served as a control for the LDF measurements and the GCF sampling. Concentrations of IL-1α in the GCF were measured using enzyme-linked immunosorbent assays. Radiographs were used to confirm EIRR. EIRR occurred in fourteen (43.8%) teeth in 32 patients. The teeth with EIRR showed diminished LDF readings when compared with controls at all visits. The LDF readings of the injured teeth continued to decrease at follow up visits. In the EIRR group, levels of IL-1α in the GCF of teeth with EIRR were increased and significantly higher than those of the control teeth at the visit when EIRR was diagnosed. The IL-1α levels were significantly higher in the EIRR group when compared to the injured teeth of patients without EIRR at the last follow-up visit. The occurrence of EIRR after mechanical trauma of permanent teeth with complete root development is accompanied by a significant reduction in the blood flow of the tooth's pulp. It is accompanied by an increase in concentrations of IL-1α in the GCF of EIRR affected teeth. The results of this pilot study identified the use of IL-1α in GCF and LDF as non-invasive markers of EIRR.

Heat Hyperemia or Reactive Hyperemia Alone Do Not Elicit Maximum Skin Blood Flow

The cutaneous circulation has been proposed as a model of generalized microvascular function which could be monitored noninvasively using laser doppler flowmetry. The response to heat hyperemia is commonly used to monitor disease or treatment related changes in microvascular function under the assumption that this represents maximum blood flow. We hypothesized that heat hyperemia alone does not elicit maximum skin blood flow. Purpose To understand how skin blood flow responds to heat hyperemia (HH), reactive hyperemia (RH), and a combination of both stimuli. Methods Ten healthy adults (30 ± 5 years; 74 ± 16.5 kg, mean ± SD) were subjected to 3 different conditions: reactive hyperemia (skin temp controlled at 33°C), heat hyperemia (skin heated to 42°C for 40 minutes), and HH + RH. Two Peltier-controlled thermomodules with laser doppler flow probes were placed on the right forearm to measure skin blood flow. A rapid release cuff on the right upper arm was inflated to 220 mmHg for 5 min to elicit RH while laser doppler flow (LDF) was monitored continuously from 1 min before cuff inflation (baseline) to 3 min after cuff release. This procedure was performed with skin temperature at 33°C and again after 40 min of local heating to 42°C. The mean of the two LDF probes was used in determining the highest 1-sec average skin blood flow for each condition. Beat-by-beat mean arterial pressure (MAP) was obtained by a photoplethysmographic sensor on the middle finger of the left hand. Cutaneous vascular conductance (CVC) was calculated as LDF / MAP. Results Both HH and RH increased LDF and CVC above baseline values (p<0.001). The highest 1-sec LDF and CVC averages were significantly higher during HH+RH when compared to RH or HH (*p < 0.001). Conclusion These results indicate that maximum blood flow and vasodilation are greater during combined heat and reactive hyperemia than during reactive hyperemia or heat hyperemia alone. Future studies should consider using a combination of HH and RH rather than HH alone to assess maximum cutaneous vasodilation.

Development of a computed tomography perfusion protocol to support large animal resuscitation research.

Adequate cerebral perfusion is crucial for a positive neurological outcome in trauma; however, it is difficult to characterize in the acute setting with noninvasive methods. Intra-arterial computed tomography perfusion may offer a solution. The aim of this study was to develop an intra-arterial computed tomography perfusion protocol for resuscitation research. The study examined intra-arterial contrast administration for computed tomography perfusion (CTP) acquisition. It consisted of three phases: intra-arterial contrast dose finding, evaluation of reproducibility, and evaluation during hypotension. Blood pressure and laser Doppler flow data were collected. In phase 1, animals underwent CTPs using several intra-arterial contrast injection protocols. In phase 2, animals underwent two CTPs 7 hours apart using the 2.5 mL/s for 3-second protocol. In phase 3, animals underwent CTPs at several pressures following a computer-controlled bleed including euvolemia and at systolic pressures of 60, 40, and 20 mm Hg. Phase 1 CTPs were evaluated for contrast-to-noise ratio. In phase 2, CTPs were compared within each animal and with laser Doppler flow using linear regression. Phase 3 CTPs were graphed against systolic pressure and fitted with a nonlinear fit. The protocol using 2.5mL/s for 3 seconds was optimal, demonstrating a contrast-to-noise ratio of 40.1 and a superior arterial input function curve compared with the 1 mL/s bolus. Cerebral blood flow demonstrated high concordance between baseline and end of study CTPs (R2 = 0.82, p < 0.001). Cerebral blood flow also compared moderately well against laser Doppler flow during 8 (R2 = 0.53, p = 0.03); however, laser Doppler flow did not perform well during hypovolemia, and the favorable concordance was not maintained (R2 = 0.45, p = 0.06). Cerebral blood flow was graphed against systolic blood pressure and fitted with a nonlinear fit (R2 = 0.95, p = 0.003). Computed tomography perfusion using intra-arterial contrast injection may offer a novel alternative to traditional CTP protocols that could prove a useful additional tool in the setting of resuscitation research.

A comparison of moist heat, dry heat, chemical dry heat and icy hot for deep tissue heating and changes in tissue blood flow.

Background: Intermittent bouts of heavy activity at greater than normal exercise intensity can cause delayed onset muscle soreness (DOMS). Several products are commercially available, all alleging to reduce DOMS. In the present investigation, 40 subjects (average age 27.0+/-4.4 years, average BMI 26.8) were assessed to determine the effect of 4 of these products on skin and muscle temperature and blood flow during 2 hours of application. These included ThermaCare Dry Heat Wraps, ThermaCare Moist Heat Wraps, Icy Hot Patches, and hydrocollator heat packs. Methods; Blood flow was measured (by laser doppler flow meter) over and in the quadriceps muscle and tissue temperature was measured (by thermistors and thermocouples) in these same areas. Results: The results of the study indicated that only ThermaCare Dry and Moist Heat Wraps both heated the muscle and increased muscle blood flow. The menthol and methyl salicylate compounds in Icy Hot cooled muscle. Skin blood flow increased 300% after the moist heat was applied after 45 minutes, low level continuous dry heat almost 256% but it took 105 minutes to reach this flow, hydrocollator heat wraps increased by 201% but only for only first 45 minutes and then back to baseline, a slight reduction in skin blood flow was seen with Icy Hot gel applied to the skin. Moist heat caused muscle temperature to increase by an average of 3.1 Deg C. Dry heat caused muscle temperature to increase by 2.2 Deg C, while hydrocollator packs increased temperature by 0.4 Deg C. Icy hot had no effect on muscle temperature. Conclusion: Continuous low level heat products had better penetration into muscle and increased blood flow the best compared to hydrocollator heat packs and Icy Hot patches.

흰쥐에서 고용량 아질산이온 함유 마늘 발효농축액에 의한 뇌혈류 변화

Nitrate–nitrite–nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO₂ SUP-/SUP on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO₂ solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO₂ diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO₂ solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO₂SUP-/SUP. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO₂SUP-/SUP caused significantly the production of NO in the cortical tissue but NaNO₂ solution with 500ppm of NO₂SUP-/SUP did not. In summary, these results suggested that F. garlic with high content of NO₂SUP-/SUP induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

Involvement of microcirculation in critical ischemia: how to identify it?

Critical limb ischemia represents the most severe pattern of peripheral arterial disease (PAD) associated with the high risk of major amputation, cardiovascular events and death. The diagnosis and management of critical limb ischemia (CLI) is often challenging. Systolic ankle and toe pressure measurements are considered to be the basic techniques for the identification of PAD. However, they provide rough insight into the dependent local tissue perfusion. Furthermore, those techniques do not enable investigation of microcirculation which has crucial role in the pathogenesis of CLI. Some patients with mild deterioration of macrocirculation develop CLI if microcirculation is affected. Investigation of perfusion on macro- and local microcirculatory level enables more effective treatment: revascularization of the angiosome-related artery. The technologies capable of assessing limb tissue oxygenation or perfusion on microcirculatory level enable direct assessment of distant tissue oxygenation. Transcutaneous oxygen tension (TcPO2) measurement which was introduced in clinical practice represents one of the objective criteria for the diagnosis of CLI. Main weakness of this technique as well as laser Doppler flow measurement is low penetrance from the skin surface. Measurement of tissue blood flow on microcirculatory level can be performed with indocyanine green fluorescent imaging (ICG), contrast-enhanced magnetic resonance and vital microscopy. ICG is promising method which provides excellent informative image of tissue perfusion. However, it offers little quantitative information. Investigation of microcirculation in patients with CLI is of outmost importance because it enables insight in local tissue perfusion and oxygenation, which represents the basis of identification of most ischemic regions and provide more successful angiosome related revascularization of an affected artery.

Ionizing radiation induces BH4 deficiency by downregulating GTP-cyclohydrolase 1, a novel target for preventing and treating radiation enteritis

Radiation enteritis (RE) is a common side effect after radiotherapy for abdominal cancer. RE pathogenesis is complicated, with no drugs available for prevention or treatments. Intestinal ischemia is a key factor in the occurrence and development of enteritis. The effect of ionizing radiation (IR) on intestinal ischemia is unknown. Deficiency of tetrahydrobiopterin (BH4) produced by GTP-cyclohydrolase 1 (Gch1) is important in ischemic diseases. This study focused on the relationship of Gch1/BH4 between intestinal ischemia in radiation enteritis. BH4 levels were analyzed by high-performance liquid chromatography in humans and rats after radiotherapy. Intestinal blood perfusion was measured by laser doppler flow imaging. Vascular ring tests determined the diastolic functions of rat mesenteric arteries. Gene, protein, and immunohistochemical staining experiments and inhibitor interventions were used to investigate Gch1 and endothelial NOS (eNOS) in rat mesenteric arteries and endothelial cells. The results showed that IR decreased BH4 levels in patients and rats after radiotherapy and decreased intestinal blood perfusion in rats. The degree of change in intestinal ischemia was consistent with intestinal villus injury. Gch1 mRNA and protein levels and nitric oxide (NO) production significantly decreased, while eNOS uncoupling in arterial and vascular endothelial cells strongly increased. BH4 supplementation improved eNOS uncoupling and NO levels in vascular endothelia after IR. The results of this study showed that downregulation of Gch1 in intestinal blood vessels after IR is an important target in RE. BH4 supplementation may prevent intestinal ischemia and improve vascular endothelial function after IR. These findings have clinical significance for the prevention and treatment of RE.

P1094PULSE AMPLITUDE OF THE TOE MEASURED WITH A PORTABLE LASER DOPPLER FLOW METER IS USEFUL FOR SCREENING OF DIALYSIS PATIENTS FOR PERIPHERAL ARTERIAL DISEASE

Abstract Background and Aims Peripheral arterial disease (PAD) occurs at a high frequency in hemodialysis (HD) patients and is known to be associated with poor outcomes. Measurement of the ankle-brachial blood pressure index (ABI) or toe brachial index (TBI) has been used for screening, diagnosis and severity determination of PAD. However, the procedures for measurement of these indices are complicated and the measurements cannot be performed during dialysis sessions. The purpose of the present study was to clarify the ability of the toe blood flow and pulse amplitude measured with a portable laser Doppler flow meter (LDF) to detect PAD in dialysis patients, in comparison with the diagnostic abilities of ABI and TBI. Methods Fourteen patients on maintenance HD participated in this study. The mean age was 65.2 years old and the mean duration of HD was 9.1 years. We measured the ABI and TBI before HD, and the blood flow and pulse amplitude on the ventral side of the first toe with a portable LDF (pocket LDF®, JMS Co., Ltd., Tokyo, Japan) during the HD session on the same day. The correlations between the blood flow / pulse amplitude in the toe and the ABI / TBI were investigated. The sensitivity and specificity of the blood flow and pulse amplitude in the toe for PAD detection were determined by a receiver operating characteristic curve analysis. Statistical analysis was performed using the Fisher’s exact test. A p value of &amp;lt;5% was considered to indicate a significant difference. Results and Discussion No significant correlation was found between the blood flow and the pulse amplitude in the toe (p = 0.454). The blood flow was not correlated with either the ABI or the TBI (p = 0.286, p = 0.115, respectively). However, the pulse amplitude showed significant correlations with both the ABI and TBI (p &amp;lt; 0.001, p &amp;lt; 0.05). When we used the general reference cutoff values for ABI and TBI of 0.9 and 0.6, respectively, the sensitivity and specificity of ABI for the detection of PAD were 0.75 and 0.75, respectively, and those of TBI were 1.0 and 0.75, respectively. On the other hand, the sensitivity and specificity of blood flow in the toe were 0.50 and 1.0, respectively, when the cutoff value was set at 23.8 mL/min. The sensitivity and specificity of the pulse amplitude were 0.75 and 1.0, respectively, when the cutoff value was set at 7.6 mL/min. These results indicate that the pulse amplitude in the toe showed a high diagnostic ability, like ABI and TBI, for the detection of PAD. Although our results in this study were obtained from a small sample size and further investigation is warranted, the pulse amplitude measured with the portable LDF was correlated well with both the ABI and TBI, and its sensitivity and specificity for the detection of PAD were also high, indicating the high diagnostic ability of the pulse amplitude for PAD. As compared to the measurement of ABI or TBI, the pulse amplitude in the toe can be easily measured with a portable LDF, even during a dialysis session. Thus, we believe that the use of a portable LDF might be of great benefit as a screening tool for PAD. Conclusion The pulse amplitude in the toe measured with a portable LDF may have the potential to become a novel easily measurable index in the screening of dialysis patients for PAD.

Protective effects of dexmedetomidine on the survival of random flaps

BackgroundRandom flaps can be used to repair wounds and improve shape and functional reconstruction, but inflammation and necrosis limit their application. Modified McFarlane flap models were constructed on the backs of rats. We hypothesized that dexmedetomidine (DEX) could improve the survival rate of ischemic random flaps. MethodsSixty rats were randomly divided into three groups: a low-dose DEX group (DEX-L group, 10 μg/kg/D), a high-dose DEX group (DEX-H group, 20 μg/kg/D) and a control group (0.9 % saline equivalent). On day 7 after flap construction, the survival percentage of the flap model was calculated. Hematoxylin and eosin staining (H&E) was used to evaluate the histopathological status of the flaps and microvessel density (MVD). Lead oxide/gelatin angiography was used to detect angiogenesis, and laser Doppler flow imaging (LDF) was used to detect blood perfusion. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the middle areas of the flaps were measured to show the level of oxidative stress. The expressions of Toll-like receptor (TLR4), nuclear factor-kappa B (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. ResultsDEX significantly increased the average survival percentage of the flaps and reduced ischemia and necrosis of the distal end of the flaps. SOD activity significantly increased, while MDA significantly decreased, indicating that DEX reduces oxidative damage. The expression of inflammatory immunoregulatory proteins (TLR4, NF-κB) was downregulated, and the levels of inflammatory factors (IL-1β, IL-6 and TNF-α) were lower. In addition, DEX upregulated VEGF expression, promoted angiogenesis, and increased blood perfusion. ConclusionIn random flap transplantation, a high dose of DEX is beneficial to flap survival.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = − 0.4, p = 0.009) and between vWF:Ag and TH2 (R = − 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Selective Thermal Stimulation Delays the Progression of Vasoconstriction During Body Cooling

The objective of this study was to test the feasibility of selective thermal stimulation (STS) as a method to upregulate glabrous skin blood flow. STS is accomplished by mild surface heating along the spinal cord. Four healthy subjects were tested in this study. Each participated in a control experiment and an intervention experiment (STS). Both experiments included establishing a maximum level of vasodilation, considered unique to a subject on a test day, and then cooling to a maximum level of vasoconstriction. Perfusion was measured by a laser Doppler flow probe on the index fingertip. The percent of perfusion in the range of minimum to maximum was the primary outcome variable. The data were fit to a linear mixed effects model to determine if STS had a significant influence on perfusion during whole body cooling. STS had a statistically significant effect on perfusion and increased glabrous skin blood flow by 16.3% (P < 0.001, CI (13.1%, 19.5%)) as skin temperature was decreased. This study supports the theory that STS improves the heat exchanger efficiency of palmar and plantar surfaces by increasing the blood flow.

Autoregulation assessment by direct visualisation of pial arterial blood flow in the piglet brain

Impairment of cerebrovascular autoregulation (CAR) is common after brain injury, although the pathophysiology remains elusive. The mechanisms of vascular dysregulation, their impact on brain function, and potential therapeutic implications are still incompletely understood. Clinical assessment of CAR remains challenging. Observational studies suggest that CAR impairment is associated with worse outcomes, and that optimization of cerebral blood flow (CBF) by individual arterial blood pressure (ABP) targets could potentially improve outcome. We present a porcine closed cranial window model that measures the hemodynamic response of pial arterioles, the main site of CBF control, based on changes in their diameter and red blood cell velocity. This quantitative direct CAR assessment is compared to laser Doppler flow (LDF). CAR breakpoints are determined by segmented regression analysis and validated using LDF and brain tissue oxygen pressure. Using a standardized cortical impact, CAR impairment in traumatic brain injury can be studied using our method of combining pial arteriolar diameter and RBC velocity to quantify RBC flux in a large animal model. The model has numerous potential applications to investigate CAR physiology and pathophysiology of CAR impairment after brain injury, the impact of therapeutic interventions, drugs, and other confounders, or to develop personalized ABP management strategies.

Effects of moderate and severe hypocapnia on intracerebral perfusion and brain tissue oxygenation in piglets.

Hypocapnia is a common alteration during anesthesia in neonates. To investigate the effects of hypocapnia and hypocapnia combined with hypotension (HCT) on cerebral perfusion and tissue oxygenation in anesthetized piglets. Thirty anesthetized piglets were randomly allocated to groups: moderate hypocapnia (mHC), severe hypocapnia (sHC), and HCT. Cerebral monitoring comprised a tissue oxygen partial pressure and a laser Doppler probe inserted into the brain tissue as well as a near-infrared spectroscopy (NIRS) sensor placed on the skin, measuring regional oxygen saturation. Hypocapnia was induced by hyperventilation (target PaCO2 mHC: 3.7-4; sHC: 3.1-3.3kPa) and hypotension by blood withdrawal and nitroprusside infusion (mean blood pressure: 35-38mmHg). Data were analyzed at baseline, during (Tr20, Tr40, Tr60) and after (Post20, Post40, Post60) treatment. Compared to baseline, tissue oxygen partial pressure decreased significantly and equally during all treatments (mean [SD] at baseline: mHC 35.7 [32.45]; sHC: 28.1 [20.24]; HCT 25.4 [10.3] and at Tr60: mHC: 29.9 [27.36]; sHC: 22.2 [18.37]; HCT: 18.4 [9.5] mmHg). Decreased laser Doppler flow was detected with all treatments at Tr20 (mHC: 0.9 [0.18]; sHC: 0.88 [0.15]; HCT: 0.97 [0.13] proportion from baseline). Independently of group, regional oxygen saturation varied only after reverting and not during treatment. Blood lactate, pH, HCO3- , and PaO2 increased during treatment with no differences between groups. This animal model revealed reduced cerebral blood flow and brain tissue oxygenation during hypocapnia without detectable changes in regional oxygen saturation as measured by NIRS. Changes occurred as early as during moderate hypocapnia.

Effect of the menstrual cycle phase on foot skin temperature during menthol application in young women.

According to the literature, the arteriovenous anastomoses in the peripheral parts (ex. hands and feet) respond thermal stimulation susceptibly. Thus, the feet are sensitive to cold stimulation. The aim of the present study was to investigate the effect of menstrual cycle on skin temperature (Tsk) of the foot during menthol application in young women. Tsk and partial cutaneous blood flow in the foot, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness during the preovulatory (P), luteal (L), and menstrual (M) phases during menthol application in young women using thermography, laser Doppler flowmetry, a digital blood pressure monitor, and VAS scale were examined at 25 °C. After application of the 0.5% menthol solution to the right foot, the measurements were continued for 20 min. The Tsk of the second and third right toes in the P phase were lower than that in the L phase. The Tsk of the little right toe in the P phase was lower than that in the L and M phases. No significant differences were observed in the Tsk of the dorsum of right foot, cutaneous Laser-Doppler flow in the right great toe, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness among the phases. The menstrual cycle phase did not affect Tsk in the dorsum of the foot, but it affected Tsk in some toes during menthol application.