Increase In Skin Perfusion Research Articles

Investigation of changes in the skin blood microcirculation when performing the hatha yoga breathing technique

Introduction. Yoga breathing exercises improve the ability to significantly reduce the respiratory rate. A decrease of the minute respiration volume results in compensatory reactions of the microcirculatory bed caused by changes in the gas composition. The reaction of the regulatory mechanisms of the microvascular bed can be evaluated by the optical non-invasive laser Doppler flowmetry method. The aim of the study was to assess the tissue microcirculation parameter changes in people performing yoga breathing exercises. Materials and methods. 25 volunteers performed yoga breathing exercises at a frequency of 3 times per minute, 2 times per minute, 1.5 times per minute, 1 time per minute for 5 minutes, and free breathing for 6 minutes before and after breathing exercises. Parameters aimed to defin the reaction of skin microcirculation in different body areas were simultaneously recorded in six sites by laser Doppler flowmetry using a distributed system of wearable analyzers. The parameters of tissue microcirculation recorded by the method of laser Doppler flowmetry were: the index of microcirculation (Im), nutritive blood flow (Imn), the amplitude of myogenic (Am), neurogenic (An), endothelial (Ae), respiratory (Ar) and cardiac (Ac) regulation circuits. Results. Yoga breathing exercises led to increase of microcirculation index at all breathing frequencies. Breathing at a frequency of 1.5 and 1/minute leads to a significant increase in nutritional blood flow. Low-frequency breathing exercises lead to an increase in blood pressure at the lowest breathing rates – 1.5/minute and 1/minute. The most significant changes were achieved at the lowest respiration rates (1 and 1.5/minute), that could be associated with hypoxic-hypercapnic mechanisms. Conclusion. The absence of significant changes in microcirculation parameters after low-frequency respiration during measurements in the supraorbital arteries in both groups characterizes the work of homeostatic mechanisms for maintaining brain perfusion in stressful situations for the body (low-frequency types of respiration, hypercapnia and hypoxia). When measured in the extremities, a change in the effect of the circulatory system regulatory mechanisms was observed; along with an increase in skin perfusion and the nutritional component, it can characterize the compensatory reaction of the microcirculation to respiration change.

Effects of Ice Massage Prior to an Iontophoresis Treatment Using Dexamethasone Sodium Phosphate.

Low current intensity iontophoresis treatments have increased skin perfusion over 700% from baseline potentially altering drug clearance from or diffusion to the targeted area. To determine the effects of a preceding 10-minute ice massage on subcutaneous dexamethasone sodium phosphate (Dex-P) concentration and skin perfusion during and after a 4-mA iontophoresis treatment. Controlled laboratory study. Research laboratory. Twenty-four participants (male = 12, female = 12; age = 25.6 [4.5]y, height = 173.9 [8.51]cm, mass = 76.11 [16.84]kg). Participants were randomly assigned into 2 groups: (1)pretreatment 10-minute ice massage and (2)no pretreatment ice massage. Treatment consisted of an 80-mA·minute (4mA, 20min) Dex-P iontophoresis treatment. Microdialysis probes (3 mm deep in the forearm) were used to assess Dex-P, dexamethasone (Dex), and its metabolite (Dex-Met) concentrations. Skin perfusion was measured using laser Doppler flowmetry. Microdialysis samples were collected at baseline, at conclusion of treatment, and every 20 minutes posttreatment for 60minutes. Samples were analyzed to determine Dex-Total (Dex-Total = Dex-P + Dex + Dex-Met). Skin perfusion was calculated as a percentage change from baseline. A mixed-design analysis of variance was used to determine Dex-Total and skin perfusion difference between groups overtime. There was no difference between groups (P = .476), but [Dex-Total] significantly increased over the course of the iontophoresis and posttreatment time (P < .001). Dex-P was measured in 18 of 24 participants with a mean concentration of 0.67 (1.09)μg/mL. Skin perfusion was significantly greater in the no ice treatment group (P = .002). Peak skin perfusion reached 27.74% (47.49%) and 117.39% (103.45%) from baseline for the ice and no ice groups, respectively. Ice massage prior to iontophoresis does not alter the tissue [Dex-Total] even with less skin perfusion.

Modulation of Blood Flow in the Skin of Human Legs during Transcutaneus Electrical Stimulation of the Spinal Cord

Changes in blood supply to the skin of the anterior-lateral surface of the shin of 12 healthy subjects were detected. The analysis was performed using laser Doppler flowmetry during transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz. The TSCS at T7 and L1 vertebrae level leads to a significant increase in cutaneous blood flow. With a stimulus intensity of 90% of the motor threshold, the increase in skin perfusion during stimulation at L1 was about 74%, and during stimulation at T7, 38%, relative to the baseline. We suggest that vasodilation and hyperemia of the skin during TSCS occur mainly due to the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important modulator that promotes vasodilation in TSCS. It is released by the nerve endings and the layer of endothelial cells. Inhibition of cystathionine-γ-lyase significantly reduces the increase in skin blood flow during TSCS. Therefore, it was concluded that H2S, as well as NO, is also involved in the vasodilation in the skin during TSCS.

Study protocol for an exploratory interventional study investigating the feasibility of video-based non-contact physiological monitoring in healthy volunteers by Mapping Of Lower Limb skIn pErfusion (MOLLIE)

IntroductionSkin perfusion varies in response to changes in the circulatory status. Blood flow to skin is reduced during haemodynamic collapse secondary to peripheral vasoconstriction, whereas increased skin perfusion is frequently...

Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes

Aims/hypothesisGlucagon-like peptide-1 (GLP-1) analogues reduce the risk of macrovascular disease in diabetes; however, little is known about their microvascular effects. This research examined the microvascular actions of the GLP-1 analogues liraglutide and exenatide in individuals with and without type 2 diabetes (study 1). It also explored the involvement of the GLP-1 receptor (study 2) and the nitric oxide pathway in mediating the microvascular effects of the analogues.MethodsTrial design: Studies 1 and 2 had a randomised, controlled, double-blind study design. Study 1 participants, intervention and methods: three participant groups were recruited: individuals with well-controlled type 2 diabetes, and obese and lean individuals without diabetes (21 participants per group). Liraglutide (0.06 mg), exenatide (0.5 μg) and saline (154 mmol/l NaCl; 0.9%) control were microinjected into separate sites in the dermis (forearm) in a randomised order, blinded to operator and participant. Skin microvascular perfusion was assessed by laser Doppler perfusion imaging. Outcomes were stabilised response (mean skin perfusion between 7.5 and 10 min post microinjection) and total response (AUC, normalised for baseline perfusion). Perfusion response to GLP-1 analogues was compared with saline within each group as well as between groups. Study 2 participants, intervention and methods: in healthy individuals (N = 16), liraglutide (0.06 mg) and saline microinjected sites were pretreated with saline or the GLP-1 receptor blocker, exendin-(9,39), in a randomised order, blinded to participant and operator. Outcomes were as above (stabilised response and total perfusion response). Perfusion response to liraglutide was compared between the saline and the exendin-(9,39) pretreated sites. In vitro study: the effects of liraglutide and exenatide on nitrate levels and endothelial nitric oxide synthase phosphorylation (activation) were examined using human microvascular endothelial cells.ResultsStudy 1 results: both analogues increased skin perfusion (stabilised response and total response) in all groups (n = 21 per group, p < 0.001), with the microvascular responses similar across groups (p ≥ 0.389). Study 2 results: liraglutide response (stabilised response and total response) was not influenced by pretreatment with exendin-(9,39) (70 nmol/l) (N = 15, one dataset excluded) (p ≥ 0.609). Liraglutide and exenatide increased nitrate production and endothelial nitric oxide synthase (eNOS) phosphorylation (p ≤ 0.020).Conclusions/interpretationLiraglutide and exenatide increased skin microvascular perfusion in individuals with and without well-controlled diabetes, potentially mediated, at least in part, by NO.Trial registrationClinicalTrials.gov NCT01677104.FundingThis work was supported by Diabetes UK (grant numbers: 09/0003955 and 12/0004600 [RW and JM Collins Legacy, Funded Studentship]).

Elucidating the Mechanism of Absorption of Fast-Acting Insulin Aspart: The Role of Niacinamide

PurposeFast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart containing two additional excipients: niacinamide, to increase early absorption, and L-arginine, to optimize stability. The aim of this study was to evaluate the impact of niacinamide on insulin aspart absorption and to investigate the mechanism of action underlying the accelerated absorption.MethodsThe impact of niacinamide was assessed in pharmacokinetic analyses in pigs and humans, small angle X-ray scattering experiments, trans-endothelial transport assays, vascular tension measurements, and subcutaneous blood flow imaging.ResultsNiacinamide increased the rate of early insulin aspart absorption in pigs, and pharmacokinetic modelling revealed this effect to be most pronounced up to ~30–40 min after injection in humans. Niacinamide increased the relative monomer fraction of insulin aspart by ~35%, and the apparent permeability of insulin aspart across an endothelial cell barrier by ~27%. Niacinamide also induced a concentration-dependent vasorelaxation of porcine arteries, and increased skin perfusion in pigs.ConclusionNiacinamide mediates the acceleration of initial insulin aspart absorption, and the mechanism of action appears to be multifaceted. Niacinamide increases the initial abundance of insulin aspart monomers and transport of insulin aspart after subcutaneous administration, and also mediates a transient, local vasodilatory effect.

Nicorandil reduces burn wound progression by enhancing skin blood flow

We assessed whether nicorandil, an adenosine triphosphate-sensitive K + channel opener, reduces burn wound progression in a rat comb burn model. A total of 24 rats were used. Following thermal injury, one dose of nicorandil (10 or 30 mg/kg) was administered intragastrically twice daily for 3 days. At days 1 and 3 after injury, skin was harvested for histopathological examination and protein isolation. Rats treated with the 10-mg/kg and 30-mg/kg doses of nicorandil exhibited significantly increased tissue survival in the zone of stasis at days 1 and 3 after injury. The 10-mg/kg and 30-mg/kg nicorandil doses also significantly increased skin perfusion in the zone of stasis at days 1 and 3 after injury. At 30 mg/kg, nicorandil significantly reduced hypoxia-inducible factor-1α expression in the zone of stasis at day 1 after injury and reduced inflammatory responses in the zone of stasis. The latter effect included decreased polymorphonuclear neutrophil leukocyte infiltration and interleukin-1β release at day 1 after injury. At 30 mg/kg, nicorandil also significantly reduced expression of nuclear factor-κB p65, akey transcriptional factor in the regulation of inflammatory mediators, in the zone of stasis at day 1 after injury. Our study demonstrates that a 30 mg/kg dosing schedule of nicorandil increases tissue survival in the zone of stasis by attenuating ischemia-reperfusion injury. This effect is mediated by the enhancement of skin blood flow and reduction in the inflammatory response. Therefore, our findings suggest that nicorandil has potential clinical applications for patients with burns.

The evaluation of contralateral foot circulation after unilateral revascularization procedures using indocyanine green angiography

The aim of the present study is to assess the effects of unilateral revascularization on the contralateral foot circulation using indocyanine green (ICG). From January 2016 to April 2016, a total of twenty-one patients were included in this study. The patients underwent elective unilateral revascularization at our institution and we evaluated the feet circulation by indocyanine green angiography (ICGA) tests preoperatively and postoperatively. The ICGA parameters included the magnitude of intensity from the onset of ICG to the maximum intensity (Imax), the time from the onset of ICG to the maximum intensity (Tmax), and the time required to reach the half maximum intensity from the onset of ICG (T1/2). There were significant differences in the treated limb Tmax (P = 0.016) and T1/2 (P = 0.013) values and in the contralateral limb Tmax (P = 0.013), and T1/2 (P < 0.001) values on the perioperative ICGA tests. These results reflect the increase in skin perfusion in the treated limb and the decrease in skin perfusion in the contralateral limb. Unilateral revascularization decreases contralateral foot circulation. The preoperative contralateral lesion should be evaluated when revascularization is performed.

Skin Blood Flow and Vascular Endothelium Function in Uremia

Prevalence of dermatological disorder in patients with end-stage kidney disease is estimated as 50% to 100% in various studies. Some of the skin lesions are specific for the diseases causing chronic kidney disease (CKD), some are associated with CKD, and still others are the dermatological manifestation of uremia. Microangiopathy was also found in both arterioles and venule in the skin biopsy of "normal looking" skin in patients with end-stage kidney disease. In a cross-sectional study in patients on dialysis, we measured skin blood flow (SBF) using laser Doppler device in a standardized way at various areas of lower extremities at 2 different local skin temperatures: 35°C and 44°C. Local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). SBF was impaired in CKD patients Stage 5 on HD, particularly in those with diabetes mellitus as a cause of CKD. The reduced response in the SBF to the heat in our patients may be due to decreased generation of NO in uremia. Endothelium-dependent vasodilatation in patients on dialysis and the response of the skin microcirculation to acetylcholine was diminished in hypertensive patients on dialysis. Similarly, patients with diabetes mellitus had decreased SBF during intradermal microdialysis with a NO synthase inhibitor. Multiple uremic toxins have been studied invitro and show to cause various degree of endothelial cell dysfunction. Unfortunately, no clear benefit has been described in CKD patients to different intervention aimed to reduce uremic toxin effect on endothelium. There are no long-term data on the factors which can modify endothelium function in uremia, but non pharmacologic interventions, diet, and several pharmacologic approaches could be beneficial. Measurement of SBF can be useful in evaluation of vasculopathy in CKD population and can potentially be used for assessment of vascular response during specific clinical intervention.

Effect of transcutaneous electrical spinal cord stimulation on the blood flow in the skin of lower limbs

Changes in the blood flow in the skin of the plantar surface of the hallux were investigated by laser Doppler flowmetry in eight healthy subjects during transcutaneous electrical spinal cord stimulation (tESCS) with the pulse parameters used to activate locomotion. Continuous tESCS in the area of C5–C6 vertebrae did not cause significant changes in the blood flow, while electrical stimulation at T 12–T 1 and L 1–L 2 levels resulted in an increase in skin perfusion by 22–27%. Wavelet analysis of microcirculatory fluctuations showed that tESCS induced flaxomotions in the range of sensory peptidergic fibers and enhanced the amplitude of fluctuations of microcirculation in the endothelium-dependent range. These results suggest that tESCS stimulates microcirculation in the skin mainly due to antidromic stimulation of sensory peptidergic nerve fibers, which promotes activity of microvascular endothelium, vasodilator secretion, a decrease in vascular resistance, and an increase in microcirculation.

Cows exposed to heat stress during fetal life exhibit improved thermal tolerance.

Maternal heat stress during late gestation affects calf function during postnatal life. The objective of the present study was to evaluate whether calves that experience heat stress in utero have altered thermoregulatory responses to acute heat stress later in life. Specifically, the hypothesis was that heat stress in utero would improve the response to acute heat stress at maturity. Females were born to dams exposed to heat stress or cooled during late gestation preceding their birth. All animals were raised postnatally under identical management. Twelve lactating Holstein cows that were exposed to in utero heat stress (HT) and 12 that were exposed to in utero control (CON) were used. A heat stress challenge was conducted in 3 blocks using 4 HT and 4 CON cows matched according to milk yield, stage of lactation, and parity. Each challenge consisted of transfer from a barn with shade and evaporative cooling to one with shade but no additional cooling for 48 h. The challenge was replicated twice for each block. Sweating rate, respiration rate, rectal temperature (RT), and skin temperature were measured on each cow at 0900, 1100, 1300, 1500, and 1700 h for 2 consecutive days. Mean ambient temperature across 6 challenge days was 26.15 ± 4.75°C. Tendencies for differences at 1700 h were observed between treatments for RT (HT: 39.5 ± 0.1; CON: 39.6 ± 0.1°C; = 0.065), however, there was no difference in respiration rate (HT: 77.6 ± 1.6; CON: 79.5 ± 1.6 bpm; = 0.85). Sweating rate for shaved skin (HT: 29.4 ± 2.0; CON: 36.0 ± 2.0 g/mh; = 0.057) and for non-shaved skin (HT: 22.5 ± 1.5; CON: 29.2 ± 1.2 g/mh; = 0.01) differed between groups. However, there was no effect on skin temperature at the shaved location (HT: 36.2 ± 0.2; CON: 36.0 ± 0.2°C; = 0.81), but there was a tendency for differences for the non-shaved area (HT: 35.4 ± 0.2; CON: 34.9 ± 0.2°C; = 0.097). Cows that underwent in utero heat stress had greater skin temperature at 1700 h vs. in utero control cows, which may be because HT cows increased skin perfusion, and consequently greater cooling via conduction. In utero HT cows would then have higher heat loss and reduced core body temperature, which results in lower rectal temperature and lower sweating rate when exposed to heat stress. These results support the hypothesis that heat stress in utero in late gestation increases heat tolerance at maturity by increasing capacity to dissipate heat to maintain core body temperature.

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load. Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI). Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load. Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

Microcirculatory changes during stimulation of tissue regeneration by polycaprolactone scaffold

The purpose of the study. The estimation of skin microcirculatory changes appearing in rats after subcutaneous implantation of polycaprolactone (PCL) scaffolds. Materials and methods. The experiments were conducted on 3 groups of rats: comparison group - the animals exposed to surgical intervention to the extent equivalent to matrix implantation, negative control group - animals subcutaneously implanted with non-biocompatible matrix; and experimental - rats subcutaneously implanted by PCL-scaffold. Skin microcirculation was analyzed by Lazer Doppler flowmetry (LDF) on the 7th, 14th and 21st day of the experiment. Morphological analysis of soft tissue complex and matrix samples was carried out on the 21st day of the experiment for scaffold biocompatibility verification. Results. It has been found that moderate increase in skin perfusion of animals in the comparison group over the surgical intervention area is not accompanied by the changes of active mechanisms of blood flow modulation and is completely resolved by the 21st day of the experiment. In negative control group, skin perfusion over the implantation area is 2 times higher than in controls in the period from 7th to 21st day of the experiment and this is accompanied by the significant increase of neurogenic and myogenic blood flow oscillation amplitudes. In the course of morphological analysis, these animals have demonstrated active inflammatory response. In the experimental group, perfusion changes are comparable with those in the comparison group and they resolve completely by the 21st day of the experiment. Morphological analysis suggests that by the 21st day of the experiment PLC-scaffold is evenly colonized by connective tissue cells and is vascularized. At the same time, reactive changes of adjacent tissues have not been detected. Conclusion. Skin microcirculatory changes over the scaffold implantation area correspond to the morphological pattern of tissue reactions which allows using LDF for dynamic estimation of scaffold biocompatibility in the course of subcutaneous implantation tests. This data suggest good PLC-scaffold biocompatibility which proves the prospects of its practical application in the tissue engineering.

Negative Pressure Wound Therapy on Closed Surgical Wounds With Dead Space: Animal Study Using a Swine Model.

BackgroundClosed incisional wound surgery frequently leaves dead space under the repaired skin, which results in delayed healing. The purpose of this study was to evaluate the effect of negative pressure wound therapy (NPWT) on incisional wounds with dead space after primary closure by evaluating the fluid volume through the suction drain, blood flow of the skin, tensile strength, and histology of the wounds.MethodsBilateral 25-cm-long incisional wounds with dead space were created on the back of 6 pigs by partially removing the back muscle and then suturing the skin with nylon sutures. NPWT (experimental group) or gauze dressing (control group) was applied over the closed incision for 7 days. Analysis of the wound included monitoring the amount of closed suction drain, blood perfusion unit, tensile strength of the repaired skin, and histology of the incision site.ResultsThe drainage amount was significantly reduced in the experimental group (49.8 mL) compared to the control group (86.2 mL) (P = 0.046). Skin perfusion was increased in the experimental group with statistical significance compared to the control group (P = 0.0175). Collagen staining was increased in the experimental group. The tensile strength of the incision site was significantly higher in the experimental group (24.6 N at 7 days, 61.67 N at 21 days) compared to the control group (18.26 N at 7 days, 50.05 N at 21 days) (P = 0.02).ConclusionThis study explains some of the mechanism for using NPWT in closed incision wounds with dead space. It demonstrates that NPWT significantly reduces drainage amount, increases skin perfusion, increases tensile strength, and has the tendency to promote collagen synthesis for closed wound with dead space indicating enhanced healing.

Relationship of peripheral neuropathy grades with increase of skin perfusion by compression therapy for breast cancer patients.

182 Background: Chemotherapy-induced peripheral neuropathy (CIPN) has become a substantial problem because of specific cytotoxic agents such as nab-paclitaxel, oxaliplatin, and eribulin. In addressing CIPN-related side effects caused by nab-PTX, we previously reported better CTCAE v4.0 grades and superior nab-PTX dose maintenance in breast cancer treatment adopting our 3S approach. Our 3S approach combines compression therapy (stockings and sleeves applied 24 hours from the beginning of nab-PTX administration) with medication therapy (selected prophylactic medications goshajinkigan, lafutidine, and mecobalamin applied over the course of treatment). In revisiting how stocking use restored skin perfusion levels decreased by nab-PTX chemotherapy, we examined whether the skin perfusion increases differ by CIPN grade. Methods: Using a laser Doppler blood flow meter with integrated probe (NL-101 Nahri Nexis Japan), we measured the skin perfusion of the lower limbs before and after stocking use across four groups: three groups of 3S prophylactics-treated nab-PTX patients divided by CIPN grade (Grade 0 [G0, n=12], Grade 1 [G1, n=20], Grades 2 and 3 combined [G2+3, n=12]), and one control group of healthy volunteers (GH, n=50). Results: In the control group (GH), the mean increase in skin perfusion level (mL/min/100g) after wearing stockings was 0.90 (SD= 3.36). For the 3S prophylactic treatment patients, the mean increase was 4.25 (4.98) in the G0 group, 2.11 (4.93) in the G1 group, and 2.69 (2.53) in the G2+3 group. ANOVA analysis indicated a significant difference in skin perfusion increase among the groups (p=0.0493). Analysis between the groups indicated significance in the G0 group increase over the control group increase (p=0.0255). Conclusions: CIPN was previously shown to decrease skin perfusion; in the current study skin perfusion responsiveness to stockings differed significantly between chemotherapy patients and healthy volunteers. Restorative skin perfusion increase is potentially related with alleviating CIPN grade, for which further evaluation is needed.

High intensity interval training at overspeed in a lower body positive pressure treadmill improves performance in trained runners

Introduction: Exercise training of the lower limbs mediates localised conduit and resistance artery adaptations in the active region and systemic adaptations in the upper limbs. These changes to the vasculature are largelymediated through elevations in shear stress. Whether microcirculatory vascular responses to lower limb training occur systemically, and whether shear stress contributes to such adaptations, is currently unknown. Methods: Nine subjects completed an 8-week cycle ergometer training study, with unilateral cuff inflation around the forearm to unilaterally manipulate upper limb blood flow and shear stress during each exercise bout. To test skin microvascular function at 0, 4 and 8 weeks of exercise training, we measured laser-Doppler skin flux in response to localised disk heating at 33, 42 and 44 ◦C. Cutaneous vascular conductance was derived from skin flux and blood pressure values. Results: Acutely, the onset of cycling increased skin flux (12.1±4.1 to 131.7±35.0 PU) and temperature (31.7±0.4 to 33.6±0.9 ◦C), whilst in the cuffed arm (60mmHg) skin flux (11.91±2.22 to 52.92PU) and temperature (31.5±0.3 to 31.7±0.8 ◦C) responses were attenuated or absent (2-way ANOVA interaction-effect; both P<0.001). Chronically, after 8 weeks of cycling, skin flux responses during the plateau phase of heating at 42 ◦C (3.19±0.32 to 2.38±0.41PU/mmHg) and 44 ◦C (3.65±0.30 to 2.84±0.44PU/mmHg) were significantly lower in the uncuffed arm, but unchanged in the cuffed limb at (42 ◦C: 3.10±0.36 to 2.76±0.30PU/mmHg, 44 ◦C: 3.70±0.39 to 3.46±0.30PU/mmHg). Discussion: Cycling exercise is associated with increased skin perfusion in the upper limbs, an effect which is ameliorated by placement of a pressure cuff. Cycle training decreased the skin vasodilator response to an identical local heating stimulus, suggesting enlargement of the capillary bed and associated increase in skin blood flow transit time. We speculate that this impact of leg exercise training in the upper limbs may enhance systemic heat loss following training. No changes in the contra-lateral cuffed arm were apparent, suggesting that repeated increases in shear stress may mediate some of this adaptation in the skin microcirculation as a result exercise training.

Systemic adaptations to exercise training in skin microcirculation in humans

Introduction: Exercise training of the lower limbs mediates localised conduit and resistance artery adaptations in the active region and systemic adaptations in the upper limbs. These changes to the vasculature are largelymediated through elevations in shear stress. Whether microcirculatory vascular responses to lower limb training occur systemically, and whether shear stress contributes to such adaptations, is currently unknown. Methods: Nine subjects completed an 8-week cycle ergometer training study, with unilateral cuff inflation around the forearm to unilaterally manipulate upper limb blood flow and shear stress during each exercise bout. To test skin microvascular function at 0, 4 and 8 weeks of exercise training, we measured laser-Doppler skin flux in response to localised disk heating at 33, 42 and 44 ◦C. Cutaneous vascular conductance was derived from skin flux and blood pressure values. Results: Acutely, the onset of cycling increased skin flux (12.1±4.1 to 131.7±35.0 PU) and temperature (31.7±0.4 to 33.6±0.9 ◦C), whilst in the cuffed arm (60mmHg) skin flux (11.91±2.22 to 52.92PU) and temperature (31.5±0.3 to 31.7±0.8 ◦C) responses were attenuated or absent (2-way ANOVA interaction-effect; both P<0.001). Chronically, after 8 weeks of cycling, skin flux responses during the plateau phase of heating at 42 ◦C (3.19±0.32 to 2.38±0.41PU/mmHg) and 44 ◦C (3.65±0.30 to 2.84±0.44PU/mmHg) were significantly lower in the uncuffed arm, but unchanged in the cuffed limb at (42 ◦C: 3.10±0.36 to 2.76±0.30PU/mmHg, 44 ◦C: 3.70±0.39 to 3.46±0.30PU/mmHg). Discussion: Cycling exercise is associated with increased skin perfusion in the upper limbs, an effect which is ameliorated by placement of a pressure cuff. Cycle training decreased the skin vasodilator response to an identical local heating stimulus, suggesting enlargement of the capillary bed and associated increase in skin blood flow transit time. We speculate that this impact of leg exercise training in the upper limbs may enhance systemic heat loss following training. No changes in the contra-lateral cuffed arm were apparent, suggesting that repeated increases in shear stress may mediate some of this adaptation in the skin microcirculation as a result exercise training.

Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.

Skin perfusion and pain evaluation with different local anaesthetics in a double blind randomized study following digital nerve block anaesthesia

Supplementing a local anaesthetic with epinephrine has advantages in hand surgery: faster onset of anaesthesia, extended effect of anaesthetics with prolonged pain reduction, decreased bleeding into the operative field, and abandoned need for tourniquet. We hypothesized that the use of ropivacaine with epinephrine additive in digits allows good skin perfusion rates with prolonged pain reduction. In this prospective, double-blinded, randomized study with 20 volunteers (80 fingers, without operation) the chronological course of changes in digit blood flow, post injection pain status and complication rates after two-injection dorsal technique anaesthetic block with ropivacaine (group 1: ropivacaine 0.75%, group 2: ropivacaine 0.75% and epinephrine 1 : 1.000.000, group 3: local tumescent anaesthesia 0.15% TLA: ropivacaine, lidocaine, saline solution plus epinephrine 1 : 1.000.000) were examined. As a control group, injection of 2% lidocaine in the way with 20 minutes tourniquet (group 4) was used. Group 1 showed increased skin perfusion with a maximum of 160.2%, group 2 showed no significant changes with a following significant increase of skin perfusion (+66.6%). In group 3, a significant reduction (-54.1%) was followed by an increase of skin perfusion (+45.7%). In the control group (group 4) the skin perfusion was decreased (-66.2%) and increased significantly after opening the tourniquet (+248.1%). The longest pain reduction was shown for ropivacaine 0.75% and epinephrine with 18.0 hours (group 2); the other groups were between 4.6 to 8.1 hours. Using ropivacaine with epinephrine additive in digits could improve the intra-, and postoperative terms.

Microcirculation as determined by iontophoresis in SLE-patients and controls

The risk of cardiovascular disease (CVD), microangiopathy and prevalence of atherosclerotic plaques are increased in Systemic Lupus Erythematosus (SLE). As systemic endothelial dysfunction is one of the earliest signs of these vascular outcomes in the general population we assessed skin microvascular endothelial function in SLE patients. Endothelial function in skin was tested with local application of acetylcholine (inducing endothelium-dependent vasodilatation) and any concomitant increase in skin perfusion was measured with Laser Doppler Fluxmetry (LDF) in 84 SLE-patients (83% women, mean age 47 years) and 81 age and sex matched controls. Common carotid intima-media thickness (cIMT) and plaque occurrence were also determined using B-mode ultrasound. There were no significant differences in skin microvascular endothelial function between SLE-patients and controls. In the SLE group, endothelial function did not vary in relation to skin manifestations, Raynaud's phenomenon, nephritis or plaque occurrence. In SLE patients with CVD, however, endothelial function was impaired. Skin microvascular endothelial function is associated with CVD but not with early signs of atherosclerosis in SLE-patients. The endothelial function is not different in SLE-patients as compared to controls.