Increase In Tissue Blood Flow Research Articles

Local alternating heat and cold stimulation affects hemodynamics and oxygenation in fatigued muscle tissue and autonomic nervous activity: a single-arm interventional study

BackgroundLocal alternating heat and cold stimulation as an alternative to contrast bath may cause intermittent vasoconstriction and vasodilation, inducing a vascular pumping effect and consequently promoting increased tissue blood flow and oxygenation. This study aimed to examine the effects of local alternating heat and cold stimulation, using a wearable thermal device, on the hemodynamics of fatigued muscle tissue and autonomic nervous activity.MethodsTwenty healthy individuals experienced fatigue in the periarticular muscles of the shoulder joint due to a typing task. Local alternating heat and cold stimulations were then applied to the upper trapezius muscle. Muscle hardness was measured using a muscle hardness meter, and muscle tissue hemodynamics and oxygenation were evaluated using near-infrared spectroscopy before and after the stimulation. Autonomic nervous activity was also evaluated using heart rate variability.ResultsAlternating heat and cold stimulation decreased muscle hardness of the fatigued trapezius muscle from 1.38 ± 0.15 to 1.31 ± 0.14 N (P < 0.01). The concentration of total hemoglobin in the trapezius muscle tissue increased from − 0.21 ± 1.36 to 2.29 ± 3.42 µmol/l (P < 0.01), and the tissue hemoglobin oxygen saturation also increased from 70.1 ± 5.4 to 71.1 ± 6.0% (P < 0.05). Additionally, the heart rate variability parameter, which is an index of sympathetic nervous activity, increased from 3.82 ± 2.96 to 6.86 ± 3.49 (P < 0.01). A correlation was found between increased tissue hemoglobin oxygen saturation and increased parameters of sympathetic nervous activity (r = 0.50, P < 0.05).ConclusionsLocal alternating heat and cold stimulation affected the hemodynamic response in fatigued muscle tissue and autonomic nervous activity. This stimulation is more efficient than conventional contrast baths in terms of mobility and temperature control and has potential as a new versatile therapeutic intervention for muscle fatigue.Trial registrationUMIN-CTR (UMIN000040087: registered on April 7, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045710. UMIN000040620: registered on June 1, 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046359).

Оценка эффективности применения радиочастотного воздействия в лечении вульвовагинальной слабости

Aim: to study the effiacy and safety of the vulvovaginal laxity treatment using non-ablative radiofrequency — dynamic quadripolar radiofrequency (DQRF™). Patients and Methods: the study included 79 female patients of reproductive age (35 to 42 y.o.) who were diagnosed with second-degree uterine prolapse according to the POP-Q system after a preliminary examination. The female patients were divided into 2 groups. Main group included 47 female patients who underwent the continuous DQRF™ to the internal genital organs four times with an interval of 7 days using the EVA™ device with intravaginal and external attachments. Comparison group included 32 female patients who performed a set of Kegel exercises for 4 months to correct vulvovaginal laxity. DQRF™ efficacy is due to thermal and oscillatory effects on tissues. Under the DQRF™, the temperature of the vaginal mucosa rises evenly to 40–42 °C, fibroblasts are activated and new connective tissue fibers are formed. The radio waves effect on microcirculation promotes the collateral formation and increases tissue blood flow, providing the metabolism acceleration in the cells of the mucous membrane, including fibroblasts. Results: 4 months after the treatment in the group 1, the trend of changes in the studied indicators turned out to be more statistically significant versus the group 2: patients less commonly noted the foreign body sensation, pollakiuria, dyspareunia, constipations. The incidence and severity of vaginal symptoms, manifestations of pelvic floor dysfunction (PFDI-20) in patients decreased, and the condition of the pelvic diaphragm (PFIQ-7) with the quality of sexual life (PISQ-12) improved. The treatment effect persisted for a year. Therapy was not accompanied by the adverse events: burns in the area of radiation, pain and/or discomfort. Conclusion: the method of non-ablative radiofrequency treatment of vulvovaginal laxity is clinically effective and safe. KEYWORDS: vulvovaginal laxity, pelvic organ prolapse, non-ablative radiofrequency, pelvic floor dysfunction, dyspareunia. FOR CITATION: Kalimatova D.M., Dobrokhotova Yu.E. Efficacy evaluation concerning radiofrequency treatment of vulvovaginal laxity. Russian Journal of Woman and Child Health. 2023;6(4):347–351 (in Russ.). DOI: 10.32364/2618-8430-2023-6-4-4.

Metabolomic Analysis of Wooden Breast Myopathy Shows a Disturbed Lipid Metabolism.

Myopathies have risen strongly in recent years, likely linked to selection for appetite. For white striping (WS), causes have been identified; but for wooden breast (WB), the cause remains speculative. We used metabolomics to study the breast muscle of 51 birds that were scored for both at 35 days of age to better understand potential causes. A partial least square discriminant analysis revealed that WS and WB had distinct metabolic profiles, implying different etiologies. Arginine and proline metabolism were affected in both, although differently: WB increased arginine in breast muscle implying that the birds did not use this pathway to increase tissue blood flow. Antioxidant defenses were impeded as shown by low anserine and beta-alanine. In contrast, GSH and selenium concentrations were increased. Serine, linked to anti-inflammatory properties, was increased. Taurine, which can stabilize the cell's sarcolemma as well as modulate potassium channels and cellular calcium homeostasis, was also increased. Mineral data and depressed phosphatidylethanolamine, cAMP, and creatine-phosphate suggested compromised energy metabolism. WB also had drastically lower diet-derived lipids, suggesting compromised lipid digestion. In conclusion, WB may be caused by impaired lipid digestion triggered by a very high appetite: the ensuing deficiencies may well impair blood flow into muscle resulting in irreparable damage.

Sildenafil-Induced Revascularization of Rat Hindlimb Involves Arteriogenesis through PI3K/AKT and eNOS Activation.

Hypoxia and inflammation play a major role in revascularization following ischemia. Sildenafil inhibits phosphodiesterase-5, increases intracellular cGMP and induces revascularization through a pathway which remains incompletely understood. Thus, we investigated the effect of sildenafil on post-ischemic revascularization. The left femoral artery was ligated in control and sildenafil-treated (25 mg/kg per day) rats. Vascular density was evaluated and expressed as the left/right leg (L/R) ratio. In control rats, L/R ratio was 33 ± 2% and 54 ± 9%, at 7- and 21-days post-ligation, respectively, and was significantly increased in sildenafil-treated rats to 47 ± 4% and 128 ± 11%, respectively. A neutralizing anti-VEGF antibody significantly decreased vascular density (by 0.48-fold) in control without effect in sildenafil-treated animals. Blood flow and arteriolar density followed the same pattern. In the ischemic leg, HIF-1α and VEGF expression levels increased in control, but not in sildenafil–treated rats, suggesting that sildenafil did not induce angiogenesis. PI3-kinase, Akt and eNOS increased after 7 days, with down-regulation after 21 days. Sildenafil induced outward remodeling or arteriogenesis in mesenteric resistance arteries in association with eNOS protein activation. We conclude that sildenafil treatment increased tissue blood flow and arteriogenesis independently of VEGF, but in association with PI3-kinase, Akt and eNOS activation.

Prolonged blockade of the cervical sympathetic nerve by stellate ganglion block accelerates therapeutic efficacy in trigeminal neuropathy

Stellate ganglion block (SGB) is effective in treating head and neck pain and neuropathic diseases by increasing tissue blood flow through its sympatholytic effect. This study aimed to investigate the relationship between duration of cervical sympathetic nerve block by SGB and its therapeutic efficacy against trigeminal neuropathy after orthognathic surgery. Twenty-eight patients with trigeminal neuropathy were randomly assigned to two groups (mepivacaine and levobupivacaine) according to the drug used for SGB. Increased blood flow, which is a symptom of sympathetic blockade, was recorded for 180 min after SGB. Current perception threshold, warm or cool detection threshold, and tactile detection threshold were measured preoperatively, postoperatively, on day 10 after initiation of SGB, and 3 months postoperatively to compare therapeutic efficacy between the groups. The levobupivacaine group had a significantly longer duration of increased blood flow compared with the mepivacaine group. Values of current perception threshold, warm and cool detection threshold, and tactile detection threshold significantly improved in the levobupivacaine group on day 10 after initiation of SGB and 3 months postoperatively. A prolonged increase in blood flow due to long-term sympatholytic effects accelerates the therapeutic efficacy of SGB in trigeminal neuropathy.

Impact of Stellate Ganglion Block on Tissue Blood Flow/Oxygenation and Postoperative Mandibular Nerve Hypoesthesia: A Cohort Study

Although a stellate ganglion block (SGB) increases tissue blood flow in the mandibular region, the change in tissue oxygenation after SGB and therapeutic effect of SGB for postoperative mandibular nerve hypoesthesia remain to be established. The study aim was to measure the change in tissue oxygenation in the mandibular region after SGB. To determine the variation in tissue oxygenation in the mandibular region, the tissue oxygen index (TOI; percentage of oxygenated hemoglobin in the total hemoglobin) was measured at the skin near the mental foramen bilaterally, at the primary site of unilateral SGB, achieved using 6 mL of 1% lidocaine hydrochloride, for the treatment of bilateral postoperative mandibular nerve injury. The primary outcome of this study is the temporal variation in TOI after SGB (0.5, 1, 5, 10, 15, 20, and 25 minutes after SGB), and the control group in this study is the TOI at the end of SGB injection (0 minute). All data are expressed as the mean ± standard deviation and 95% confidence interval (CI). Repeated-measures analysis of variance with Dunnett's test was used to determine parametric statistical significance. A P-value <.05 was considered statistically significant. Thirteen patients were enrolled in this study. On both the blocked and contralateral side, the TOI was significantly increased compared to that before SGB (ΔTOI at 15 minute after SGB, 5.87 ± 2.89%, P < .001, 95% CI: 4.122 to 7.617% in the blocked side, 1.88 ± 2.73%, P=.005, 95% CI: 1.877 to 2.725% in the contralateral side). Unilateral SGB using 6 mL of 1% lidocaine hydrochloride results in an increase in tissue oxygenation in the mandibular region. Based on these findings, we hypothesize that a series of SGBs may contribute to a more rapid recovery of postoperative trigeminal nerve injury.

Estimation of long-term results of complex application of laserotherapy and low-frequency electrostatic field in patients with postprothetic inflammatory complications during dental implantation

BACKGROUND: Previous studies have shown high clinical efficacy of the course combined use of a low-frequency electrostatic field and low-intensity infrared laser therapy in patients with peri-implantitis. It was shown that the use of these physiotherapeutic factors is accompanied by the development of anti-inflammatory and analgesic effects, increased tissue blood flow in the area of therapeutic exposure, as well as activation of trophic-regenerative processes that determine the degree of osseointegration of implants. However, along with resolving the issue of the current relief of clinical manifestations of peri-implantitis, an important point is the study of the long-term effect of the treatment method used. Evaluation of long-term results makes it possible to determine the duration of the preservation of the therapeutic effect, which makes it possible to determine the optimal parameters of the frequency and frequency of the therapeutic effects.&#x0D; AIMS: Evaluation of complex physiotherapeutic treatment of patients with post-prosthetic inflammatory complications during dental implantation in the long-term period (after 6 and 12 months).&#x0D; MATERIAL AND METHODS: The study was carried out with the participation of 132 patients aged 35 to 57 years with a clinically and radiologically confirmed diagnosis of class I and II peri-implantitis. All patients were divided into 4 groups by the method of simple fixed randomization. The first group (control group, 31 patients) received standard dental treatment, including professional oral hygiene, removal of dental plaque and granulation, and debridement of peri-implant pockets. In the second group (main I, 31 patients), in addition to the standard therapy, a course of laser therapy was carried out using the BTL-4000 physiotherapy apparatus. In the third group (main II, 30 patients), the standard treatment was supplemented with a course of low-frequency electrotherapy. The fourth group (main III, 31 patients), along with standard treatment, received low-frequency electrotherapy in combination with laser therapy. Long-term results were assessed 6 and 12 months after the end of therapy using clinical-functional, biochemical and psychological methods.&#x0D; RESULTS: The course combined use of a laser and a low-frequency electrostatic field as a supplement to the standard treatment protocol for patients with peri-implantitis ensures the maximum preservation of higher indicators characterizing the restoration of the functions of the dentition, aesthetic parameters of the face and an increase in the quality of life of patients in general.&#x0D; CONCLUSION: Taking into account the risk of developing a possible exacerbation of the inflammatory process, as well as the dynamics of the studied clinical and functional parameters in patients with peri-implantitis in the long-term period, it was concluded that it is necessary to conduct repeated courses of combined use of an infrared laser and low-frequency electrostatic therapy in 69 months.

The Value of Photo Biological Regulation Based on Nano Semiconductor Laser Technology in the Treatment of Hypertension Fundus Disease.

With the development of nanometer semiconductor laser technology, due to the wide range of photobiological regulation and non-invasive advantages, it is widely used in clinical research, including reducing pain, accelerating wound healing, nerve injury repair and regeneration. Increase tissue blood flow, improve anxiety and depression, and treat Parkinson's and retinal diseases. However, in many studies, the role of photobiological regulation is still controversial. There are two main problems, one is that the mechanism of photo biological regulation is not fully understood, and the other is that the specific parameters are not uniform in different treatments, such as wavelength density, power density, pulse, treatment timing, and number of treatments. In this paper, through the second question, the parameters of low-energy near-infrared light (810 nm semiconductor laser) in the treatment of fundus diseases are the main research objects. Based on understanding the parameters of low-energy lasers, cyan blue is irradiated with different energy near-infrared light. Data analysis of the actual energy obtained after the retina of the rabbit and observation and research on the cell morphology of each layer of the retina, to obtain relatively safe treatment parameters for the retina, provide theoretical data for near-infrared light in the treatment of clinical fundus disease, and make it safer to use in clinical treatment.

Protective Effect of Crocin on Liver Function and Survival in Rats With Traumatic Hemorrhagic Shock

BackgroundThis study investigated the underlying mechanism of crocin in protecting rats with traumatic hemorrhagic shock (THS) from liver injury. Materials and MethodsEighty Sprague Dawley rats were randomly divided into four groups (n = 20), namely, Sham group, THS group, crocin group, and Sodium Acetate Ringer group. A rat model of THS was induced by hemorrhage from the left femur fracture. The effects of crocin on hemodynamics, cardiac output, blood gas, animal survival rate, and liver function in the rats with THS were determined, and its relationship with oxidative stress was also explored. ResultsCrocin significantly improved the survival rate, hemodynamic parameters, increased tissue blood flow, and promoted the liver function of the THS rats. Further results indicated that crocin significantly inhibited oxidative stress in serum and liver tissue of THS rats, with increased levels of superoxide dismutase, catalase, and glutathione, and also reduced levels of malondialdehyde and myeloperoxidase levels. In addition, crocin greatly increased nuclear factor erythroid 2-related factor 2/heme oxygenase-1 level in liver tissues of THS rats. ConclusionsThe protective mechanism of crocin on the liver of THS rats may be attributed to its abilities to stabilize hemodynamics, improve cardiac output and blood gas, increase antioxidant enzyme activity, reduce serum liver enzyme levels, and promote nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway, thereby reducing oxidative stress.

Fatty acid potassium improves human dermal fibroblast viability and cytotoxicity, accelerating human epidermal keratinocyte wound healing in vitro and in human chronic wounds.

Effective cleaning of a wound promotes wound healing and favours wound care as it can prevent and control biofilms. The presence of biofilm is associated with prolonged wound healing, increased wound propensity to infection, and delayed wound closure. Anionic potassium salts of fatty acids are tested with commonly used anionic surfactants, such as sodium laureth sulphate (SLES) and sodium lauryl sulphate/sodium dodecyl sulphate (SLS/SDS). The normal human dermal cells demonstrated significantly greater viability in fatty acid potassium, including caprylic acid (C8), capric acid (C10), lauric acid (C12), oleic acid (C18:1), and linoleic acid (C18:2), than in SLES or SLS after a 24‐hour incubation. Cytotoxicity by LDH assay in a 5‐minute culture in fatty acid potassium was significantly lower than in SLES or SLS. in vitro wound healing of human epidermal keratinocytes during the scratch assay in 24‐hour culture was more significantly improved by fatty acid treatment than by SLES or SLS/SDS. In a live/dead assay of human epidermal keratinocytes, C8K and C18:1K demonstrated only green fluorescence, indicating live cells, whereas synthetic surfactants, SLES and SLS, demonstrated red fluorescence on staining with propidium iodide, indicating dead cells after SLES and SLS/SDS treatment. Potassium salts of fatty acids are useful wound cleaning detergents that do not interfere with wound healing, as observed in the scratch assay using human epidermal keratinocytes. As potassium salts of fatty acids are major components of natural soap, which are produced by natural oil and caustic potash using a saponification method, this may be clinically important in wound and peri‐wound skin cleaning. In human chronic wounds, natural soap containing fatty acid potassium increased tissue blood flow based on laser speckle flowgraphs after 2 weeks (P < .05), in addition to removing the eschars and debris. Wound cleansing by natural soap of fatty acid potassium is beneficial for wound healing.

Blood flow modification attached to HIFU exposure mast cell degranulation

Introduction. One of the promising methods of treating oncological diseases is high-frequency focused ultrasound (HIFU). The high-frequency acoustic field generated by the emitters induces mechanothermal effects whose significance has not yet been fully assessed and their study will change the tactics of therapy. To analyze their role, we selected cellular perivascular regulators of local blood flow – mast cells (MCs). Changes in the microcirculation (MCT) allow us to judge the morphofunctional state of the MC. The aim of the study is to assess the state of the rat’s skin periphocal tissue blood flow and MCs morphofunctional properties after HIFU-exposure.Material and methods. Adult male Wistar rats were used. Animals were divided into 3 groups: control, non-contact local heating of the skin and HIFU-induced exposure. For HIFU, an experimental setting was used, consisting of a concave emitter H-148 S / N 010 with a central oscillation frequency of 1.4 MHz. In the averaged interference spot, the radiation intensity was 8.2 kW/cm2. The exposure duration from 150 to 700 ms. Depth of focus is about 1 mm. To assess the MCT, a laser doppler flowmeter was used. Material for the manufacture of film preparations of MCs was taken at the site of exposure and according to the standard method. MCs calculation was carried out using the software «Multimedia Catalog» taking into account their morphofunctional characteristics.Results. HIFU exposure led to a significant increase in blood flow in rat’s skin at an exposure time of 250 ms or more (p&lt;0.01). The maximum increase in perfusion was noted at 400 ms. The highest increase in tissue blood flow with local heating was observed at 45°C (p&lt;0.001). HIFU-exposure led to a significant decrease in the density of MCs in the subcutaneous fat tissue of rat’s skin compared with the control at an exposure time of 250 ms or more (p&lt;0.05) and a significant decrease in the relative number of type I cells, and an increase in type II and III, which indicates degranulation (p&lt;0.05). Similar changes in the amount and morphofunctional characteristics of MCs were observed in a series of experiments with local heating, but the changes were not so significant.Conclusions. With HIFU-induced exposure, increased MCT in the peripheral zones is observed, accompanied by processes of morphofunctional rearrangement of the MCs, which indicates a combined mechanothermal disturbance in the focus zone, which forms the spatiotemporal continuum of the thermal field.

Outcomes of Intermittent Infusion Hemodiafiltration in Patients with Cardiac Hypofunction on Maintenance Hemodialysis

Background: Following the onset of heart failure symptoms, fluid removal is usually intensified, but patients with decreased cardiac function may develop sudden hypotension due to poor plasma refilling and functional impairment of the mechanisms that maintain blood pressure. In these patients, removal of fluids then becomes difficult. Impairment of the mechanisms that maintain blood pressure can be treated with vasopressors, but intermittent infusion hemodiafiltration (I-HDF) may be effective for managing poor plasma refilling. Thus, here I-HDF was performed in patients with cardiac hypofunction who were undergoing maintenance hemodialysis (HD) in order to assess the clinical effects. Summary: Participants were 5 patients with cardiac hypofunction on maintenance HD. HD and I-HDF were performed for a total of 6 months each. A comparison was made of changes in dry weight (DW) and cardiothoracic ratio (CTR), blood test results, echocardiography findings, plasma ­refilling rate (PRR), and tissue blood flow. During I-HDF, a decrease in DW was achieved and CTR was significantly improved. Echocardiographic findings showed that left ventricular diameter improved significantly during I-HDF. Higher PRR values and increased tissue blood flow were ­observed during I-HDF compared with HD. Intermittent infusions during I-HDF prevented organ ischemia and suppressed the De Jager-Krogh phenomenon. This may be associated with the promotion of stable plasma refilling. Key Messages: Excessive fluid retention is a cause of heart failure symptoms. I-HDF facilitates removal of excessive fluid and thereby possibly contributes to the improvement of cardiac function.

Effects of Massage as a Combination Therapy with Lumbopelvic Stability Exercises as Compared to Standard Massage Therapy in Low Back Pain: a Randomized Cross-Over Study

Little is known about the effects of providing massage as a combination therapy (CT) with lumbopelvic stability training (LPST) in management of chronic nonspecific low back pain (CLBP) among elite female weight lifters. It is unclear whether massage therapy (MT) together with LPST has any additional clinical benefits for individuals with CLBP. The current study compares the therapeutic effects of CT against MT as a stand-alone intervention on pain intensity (PI), pain pressure threshold (PPT), tissue blood flow (TBF), and lumbopelvic stability (LPS) among elite weight lifters with CLBP. The study was conducted at the campus for National Olympic weight lifting training camp. A total of 16 professional female elite weight lifting athletes who were training for Olympic weight lifting competition participated in the study. A within-subject, repeated measures, crossover, single-blinded, randomized allocation study. The athletes were randomized into three sessions of CT and MT with a time interval of 24 hrs within sessions and a wash out period of four weeks between the sessions. The PI, PPT, TBF, and LPS were measured before and after each session repeatedly in both groups of intervention. The changes in the PI, PPT, TBF, and LPS were analyzed using repeated measures analysis of variance (ANOVA). The results showed that the CT significantly demonstrated greater effects in reducing pain perception (45%-51%), improving pain pressure threshold (15% up to 25%), and increasing tissue blood flow (131%-152%) than MT (p < .001). The combination therapy of massage therapy and LPST is likely to provide more clinical benefits in terms of PI, PPT, and TBF when compared to massage as a stand-alone therapy among individuals with chronic nonspecific low back pain.

Contrast Baths, Intramuscular Hemodynamics, and Oxygenation as Monitored by Near-Infrared Spectroscopy.

Contrast baths (CB) is a thermal treatment modality used in sports medicine, athletic training, and rehabilitation settings. Proposed physiological effects of CB include increasing tissue blood flow and oxygenation and decreasing tissue swelling and edema to promote better healing, improved limb function, and quicker recovery. To investigate the physiological effects of CB on the intramuscular hemodynamics and oxygenation of the lower leg muscles using near-infrared spectroscopy (NIRS), an optical method for monitoring changes in tissue oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) as well as tissue oxygen saturation index (TSI%). Descriptive laboratory study. Ten healthy men and women with a mean age of 29 (range = 17 ± 42) years, mean body mass index of 24.6 ± 3.2, and mean adipose tissue thickness of 6.4 ± 2.2 mm. Conventional CB (10-minute baseline, 4 : 1-minute hot : cold ratio) was applied to the left lower leg. Changes in chromophore concentrations of O2Hb, HHb, tHb, and TSI% of the gastrocnemius muscle were monitored during 10 minutes of baseline measurement, a 30-minute CB protocol, and 10 minutes of recovery using a spatially resolved NIRS. After a 30-minute CB protocol, increases ( P < .05) in tissue O2Hb (7.4 ± 4 μM), tHb (7.6 ± 6.1 μM), and TSI% (3.1% ± 2.3%) were observed as compared with baseline measures. Application of CB induced a transient change in the hemodynamics and oxygenation of the gastrocnemius muscle in healthy individuals. The effect of CB application in improving tissue hemodynamics and oxygenation may, therefore, support the therapeutic benefits of CB in the treatment of muscle injuries.

Calcium and electrical dynamics in lymphatic endothelium.

Endothelial cell function in resistance arteries integrates Ca2+ signalling with hyperpolarization to promote relaxation of smooth muscle cells and increase tissue blood flow. Whether complementary signalling occurs in lymphatic endothelium is unknown. Intracellular calcium and membrane potential were evaluated in endothelial cell tubes freshly isolated from mouse collecting lymphatic vessels of the popliteal fossa. Resting membrane potential measured using intracellular microelectrodes averaged ∼-70mV. Stimulation of lymphatic endothelium by acetylcholine or a TRPV4 channel agonist increased intracellular Ca2+ with robust depolarization. Findings from Trpv4-/- mice and with computational modelling suggest that the initial mobilization of intracellular Ca2+ leads to influx of Ca2+ and Na+ through TRPV4 channels to evoke depolarization. Lymphatic endothelial cells lack the Ca2+ -activated K+ channels present in arterial endothelium to generate endothelium-derived hyperpolarization. Absence of this signalling pathway with effective depolarization may promote rapid conduction of contraction along lymphatic muscle during lymph propulsion. Subsequent to a rise in intracellular Ca2+ ([Ca2+ ]i ), hyperpolarization of the endothelium coordinates vascular smooth muscle relaxation along resistance arteries during blood flow control. In the lymphatic vasculature, collecting vessels generate rapid contractions coordinated along lymphangions to propel lymph, but the underlying signalling pathways are unknown. We tested the hypothesis that lymphatic endothelial cells (LECs) exhibit Ca2+ and electrical signalling properties that facilitate lymph propulsion. To study electrical and intracellular Ca2+ signalling dynamics in lymphatic endothelium, we excised collecting lymphatic vessels from the popliteal fossa of mice and removed their muscle cells to isolate intact LEC tubes (LECTs). Intracellular recording revealed a resting membrane potential of ∼-70mV. Acetylcholine (ACh) increased [Ca2+ ]i with a time course similar to that observed in endothelium of resistance arteries (i.e. rapid initial peak with a sustained 'plateau'). In striking contrast to the endothelium-derived hyperpolarization (EDH) characteristic of arteries, LECs depolarized (>15mV) to either ACh or TRPV4 channel activation. This depolarization was facilitated by the absence of Ca2+ -activated K+ (KCa ) channels as confirmed with PCR, persisted in the absence of extracellular Ca2+ , was abolished by LaCl3 and was attenuated ∼70% in LECTs from Trpv4-/- mice. Computational modelling of ion fluxes in LECs indicated that omitting K+ channels supports our experimental results. These findings reveal novel signalling events in LECs, which are devoid of the KCa activity abundant in arterial endothelium. Absence of EDH with effective depolarization of LECs may promote the rapid conduction of contraction waves along lymphatic muscle during lymph propulsion.

Effect of ThermaCare HeatWraps and Icy Hot Cream/Patches on Skin and Quadriceps Muscle Temperature and Blood Flow

ObjectivesThe purpose of this study was to compare the effects of over-the-counter treatments—ThermaCare HeatWraps (chemical reaction to produce heat above the skin), Icy Hot Patch, and Icy Hot Cream (topically applied menthol)—on skin and deep tissue temperature. MethodsThis was a longitudinal crossover study. On each of 3 days, a ThermaCare HeatWrap, Icy Hot Cream, or Icy Hot Patch was applied randomly over the quadriceps muscle in 15 healthy volunteers with normal body mass. Skin and muscle temperature and blood flow were measured by laser flowmetry every 15 minutes for 2 hours. ResultsAfter 2 hours, mean temperature decreased by 2.1°C (7.0%; P = .02) in skin and 1.0°C (2.9%; P = .01) in muscle with Icy Hot Cream. Icy Hot Patch decreased skin and muscle temperature by 1.7°C (5.4%; P = .03) and 1.3°C (3.8%; P = .01), respectively. In contrast, ThermaCare raised skin and muscle temperature by 7.8°C (25.8%; P = .001) and 2.7°C (7.7%; P = .002), respectively; both were significantly warmer with ThermaCare vs either Icy Hot product (all P < .007). Icy Hot products produced a net decrease in skin blood flow (Cream: 56.7 flux [39.3%; P = .003]; Patch: 19.1 flux [16.7%; P = .045]). Muscle blood flow decreased with the Patch (6.7 flux [7.0%; P = .02]). After a period of fluctuations, Icy Hot Cream produced a net increase vs baseline of 7.0 flux (16.9%; P = .02). ThermaCare more than doubled blood flow in skin (83.3 flux [109.7%; P = .0003]) and muscle (25.1 flux [148.5%; P = .004]). ConclusionsIn this group of 15 healthy volunteers, ThermaCare HeatWraps provided the greatest degree of tissue warming and increase in tissue blood flow.

Improvements in tissue blood flow and lumbopelvic stability after lumbopelvic core stabilization training in patients with chronic non-specific low back pain.

[Purpose] This study investigated the effects of lumbopelvic stabilization training on tissue blood flow changes in the lumbopelvic region and lumbopelvic stability compared to placebo treatment and controlled intervention among patients with chronic non-specific low back pain. [Subjects and Methods] A total of 25 participants (7 males, 18 females; mean age, 33.3 ± 14.4 years) participated in this within-subject, repeated-measures, double-blind, placebo-controlled comparison trial. The participants randomly underwent three types of interventions that included lumbopelvic stabilization training, placebo treatment, and controlled intervention with 48 hours between sessions. Lumbopelvic stability and tissue blood flow were measured using a pressure biofeedback device and a laser Doppler flow meter before and after the interventions. [Results] The repeated-measures analysis of variance results demonstrated a significant increase in tissue blood flow over the lumbopelvic region tissues for post- versus pre-lumbopelvic stabilization training and compared to placebo and control interventions. A significant increase in lumbopelvic stability before and after lumbopelvic stabilization training was noted, as well as upon comparison to placebo and control interventions. [Conclusion] The current study supports an increase in tissue blood flow in the lumbopelvic region and improved lumbopelvic stability after core training among patients with chronic non-specific low back pain.

Membrane potential governs calcium influx into microvascular endothelium: integral role for muscarinic receptor activation.

In resistance arteries, coupling a rise of intracellular calcium concentration ([Ca(2+)]i) to endothelial cell hyperpolarization underlies smooth muscle cell relaxation and vasodilatation, thereby increasing tissue blood flow and oxygen delivery. A controversy persists as to whether changes in membrane potential (V(m)) alter endothelial cell [Ca(2+)]i. We tested the hypothesis that V(m) governs [Ca(2+)]i in endothelium of resistance arteries by performing Fura-2 photometry while recording and controlling V(m) of intact endothelial tubes freshly isolated from superior epigastric arteries of C57BL/6 mice. Under resting conditions, [Ca(2+)]i did not change when V(m) shifted from baseline (∼-40 mV) via exposure to 10 μM NS309 (hyperpolarization to ∼-80 mV), via equilibration with 145 mm [K(+)]o (depolarization to ∼-5 mV), or during intracellular current injection (±0.5 to 5 nA, 20 s pulses) while V(m) changed linearly between ∼-80 mV and +10 mV. In contrast, during the plateau (i.e. Ca(2+) influx) phase of the [Ca(2+)]i response to approximately half-maximal stimulation with 100 nm ACh (∼EC50), [Ca(2+)]i increased as V(m) hyperpolarized below -40 mV and decreased as V(m) depolarized above -40 mV. The magnitude of [Ca(2+)]i reduction during depolarizing current injections correlated with the amplitude of the plateau [Ca(2+)]i response to ACh. The effect of hyperpolarization on [Ca(2+)]i was abolished following removal of extracellular Ca(2+), was enhanced subtly by raising extracellular [Ca(2+)] from 2 mm to 10 mm and was reduced by half in endothelium of TRPV4(-/-) mice. Thus, during submaximal activation of muscarinic receptors, V(m) can modulate Ca(2+) entry through the plasma membrane in accord with the electrochemical driving force.

VEGF-induced blood flow increase causes vascular hyper-permeability in vivo

VEGF is known to cause vascular leak, its detailed mechanisms in vivo remain unclear. Here, we investigated the mechanisms underlying VEGF-induced vascular hyper-permeability focusing on two major regulators of vascular permeability: blood flow and endothelial barrier function. Administration of VEGF caused vascular hyper-permeability and tissue swelling in mouse ears, which were abolished by VEGF receptor-2 blockade. Intravital imaging showed that VEGF dilated ear arteries but not veins, and laser Doppler velocimetry showed that VEGF quickly increased tissue blood flow along with arterial dilation. Whole-mount immunostaining showed that VEGF phosphorylated endothelial nitric oxide synthase (eNOS) at residue Ser1177 and disrupted the alignment of vascular endothelial-cadherin (VE-cadherin) around the endothelial cell borders in mouse ear skin, indicating endothelial nitric oxide (NO) production and barrier disruption. Administration of the nitric oxide synthesis inhibitor, L-NAME, as well as the vasoconstrictor phenylephrine, abolished all VEGF-induced responses, including blood flow increase, dye leakage, and tissue swelling. However, these two treatments did not alter the intracellular localization of VE-cadherin-induced by VEGF. These observations underscore the importance of vascular dilation and, subsequent increase in blood flow, as well as, endothelial barrier disruption in the mechanisms of VEGF-induced vascular hyper-permeability.

Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation.

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators. Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10(8) IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (P<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively; P<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (P<0.01), whereas inhibition of adenosine-A2a receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%-50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb. Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase.