The vascular response to acute sauna heating is similar in young and middle-aged adults.

Sauna has been linked to a reduction of cardiovascular disease risk and is a promising nonpharmacological treatment for populations at risk of cardiovascular disease. This study examined the vascular response to an acute bout of sauna heating in young and middle-aged individuals. Ten young (25 ± 4 yr, 6 males and 4 females) and eight middle-aged adults (56 ± 4 yr, 4 males and 4 females) underwent 40 min of sauna exposure at 80°C. Esophageal and intramuscular temperatures, brachial and superficial femoral artery blood flow, artery diameter, and shear rates were recorded at baseline and following heat exposure. Brachial artery flow-mediated dilation (FMD) was measured at baseline and following 90 min of recovery. Esophageal and muscle temperatures increased similarly in the young and middle-aged adults by 1.5 ± 0.53 and 1.95 ± 0.70°C, respectively (P < 0.05). The shear rate increased by 170-200% (P < 0.001), while blood flow increased by 180-390% (P < 0.001) in the superficial femoral and brachial arteries, respectively, and did not differ between age groups (P = 0.190-0.899). Systolic blood pressure was reduced from 135 ± 17 to 122 ± 20 mmHg (P = 0.017) in middle-aged participants. These data indicate that young and middle-aged adults have similar vascular responses to acute sauna heating.NEW & NOTEWORTHY Sauna therapy has been shown to improve cardiovascular health and function in older adults and individuals with cardiovascular disease risk factors. Specifically, improvements in vascular function have been reported and have been attributed to the increased hemodynamic stimuli on the vasculature associated with thermal stress. The present study quantified this hemodynamic response to a sauna protocol associated with improved cardiovascular health across the lifespan. Our data show that middle-aged adults have the same shear rate and blood flow response to sauna as young adults.

Thermo-haemodynamic coupling during regional thigh heating: Insight into the importance of local thermosensitive mechanisms in blood circulation.

A positive relationship between local tissue temperature and perfusion exists, with isolated limb-segment hyperthermia stimulating hyperaemia in the heated region without affecting the adjacent, non-heated limb segment. However, whether partial-limb segment heating evokes a heightened tissue perfusion in the heated region without directly or reflexly affecting the non-heated tissues of the same limb segment remains unknown. This study investigated, in 11 healthy young adults, the lower limb temperature and haemodynamic responses to three levels of 1 h upper-leg heating, none of which alter core temperature: (1) whole-thigh (WTH; water-perfused garment), (2) quadriceps (QH; water-perfused garment) and (3) partial-quadriceps (PQH; pulsed shortwave diathermy) heating. It was hypothesised that perfusion would only increase in the heated regions. WTH, QH and PQH increased local heated tissue temperature by 2.9 ± 0.6, 2.0 ± 0.7 and 2.9 ± 1.3°C (P < 0.0001), respectively, whilst remaining unchanged in the non-heated hamstrings and quadriceps tissues during QH and PQH. WTH induced a two-fold increase in common femoral artery blood flow (P < 0.0001) whereas QH and PQH evoked a similar ∼1.4-fold elevation (P ≤ 0.0018). During QH and PQH, however, tissue oxygen saturation and laser-Doppler skin blood flow in the adjacent non-heated hamstrings or quadriceps tissues remained stable (P > 0.5000). These findings in healthy young humans demonstrate a tight thermo-haemodynamic coupling during regional thigh heating, providing further evidence of the importance of local heat-activated mechanisms on the control of blood circulation.

Lower limb hyperthermia augments functional hyperaemia during small muscle mass exercise similarly in trained elderly and young humans.

NEW FINDINGS: What is the central question of the study? Ageing is postulated to lead to underperfusion of human limb tissues during passive and exertional hyperthermia, but findings to date have been equivocal. Thus, does age have an independent adverse effect on local haemodynamics during passive single-leg hyperthermia, single-leg knee-extensor exercise and their combination? What is the main finding and its importance? Local hyperthermia increased leg blood flow over three-fold and had an additive effect during knee-extensor exercise with no absolute differences in leg perfusion between the healthy, exercise-trained elderly and the young groups. Our findings indicate that age per se does not compromise lower limb hyperaemia during local hyperthermia and/or small muscle mass exercise. ABSTRACT: Heat and exercise therapies are recommended to improve vascular health across the lifespan. However, the haemodynamic effects of hyperthermia, exercise and their combination are inconsistent in young and elderly people. Here we investigated the acute effects of local-limb hyperthermia and exercise on limb haemodynamics in nine healthy, trained elderly (69 ± 5 years) and 10 young (26 ± 7 years) adults, hypothesising that the combination of local hyperthermia and exercise interact to increase leg perfusion, albeit to a lesser extent in the elderly. Participants underwent 90 min of single whole-leg heating, with the contralateral leg remaining as control, followed by 10 min of low-intensity incremental single-leg knee-extensor exercise with both the heated and control legs. Temperature profiles and leg haemodynamics at the femoral and popliteal arteries were measured. In both groups, heating increased whole-leg skin temperature and blood flow by 9.5 ± 1.2°C and 0.7 ± 0.2 L min-1 (>3-fold), respectively (P < 0.0001). Blood flow in the heated leg remained 0.7 ± 0.6 and 1.0 ± 0.8 L min-1 higher during exercise at 6 and 12 W, respectively (P < 0.0001). However, there were no differences in limb haemodynamics between cohorts, other than the elderly group exhibiting a 16 ± 6% larger arterial diameter and a 51 ± 6% lower blood velocity following heating (P < 0.0001). In conclusion, local hyperthermia-induced limb hyperperfusion and/or small muscle mass exercise hyperaemia are preserved in trained older people despite evident age-related structural and functional alterations in their leg conduit arteries.

Determination of light pressing pressure for improving foot skin blood flow in type 2 diabetic patients.

OBJECTIVE: Traditional Thai massage is one of the alternative treatments for diabetic feet. However, the specific amount of pressing pressure applied to the foot during Thai foot massage is unknown. This study aimed to evaluate the effect of light pressing pressure on foot skin blood flow in type 2 diabetic patients. METHODES: A single-arm repeated measures was conducted. Forty-three participants were recruited via the subjective examination and screening using the Michigan Neuropathy Screening Instrument. To obtain foot skin blood flow by laser doppler blood flowmetry, a probe was pasted on the 1st distal phalange of the big toe. Light pressure at a single point was applied on the plantar skin fold between the bases of the second and third toes by using the digital algometer. The pressure was applied gently, then increased slightly until the participant started to feel some minor discomfort. Patients were asked to rate their pain intensity using the visual analogue scale. RESULTS: The average pressing pressure without discomfort was 3.55 ± 1.04 kg/cm2. The foot skin blood flow increased significantly immediately after the pressing pressure, and this increase represented about 1.9 times when compared with the baseline (p < 0.001). CONCLUSION: The application of light pressing pressure could be used as a basic standard criterion for massage to improve the foot skin blood flow in type 2 diabetic patients.

Acute effects of electrostimulation and blood flow restriction on muscle thickness and fatigue in the lower body.

Neuromuscular electrical stimulation (NMES) in combination with blood flow restriction (BFR) enhances muscle hypertrophy and force-generating capacity. The present study aimed to investigate the acute effects of BFR and NMES, both in isolation and in combination, on muscle thickness (MT) and fatigue in the lower body of 20 young healthy subjects. Different stimuli were applied for 25 min, defined by the combination of BFR with high- and low-frequency NMES, and also isolated BFR or NMES. Changes in MT were then evaluated by ultrasound of the rectus femoris (RF) and vastus lateralis (VL) muscles at the end of the session (POST) and 15 min later (POST 15'). Lower limb fatigue was evaluated indirectly by strength performance. Results showed that RF MT was higher under the combined protocol (BFR + NMES) or isolated BFR than under NMES - regardless of the frequency - both at POST (p ≤ 0.018) and POST 15' (p ≤ 0.016). No significant changes in MT were observed under isolated NMES or BFR at POST 15' when compared with basal values (p ≥ 0.067). No significant differences were observed for VL MT between conditions (p = 0.322) or for fatigue between conditions (p ≥ 0.258). Our results indicate that a combination of BFR and NMES acutely increases MT in sedentary subjects. Also, although not significantly, BFR conditions had a greater tendency to induce fatigue than isolated NMES.HighlightsThe combination of blood flow restriction (BFR) and neuromuscular electrical stimulation (NMES) produces higher acute cell swelling than the isolated application of either NMES or BFR.BFR in isolation appears to produce greater cell swelling than NMES, regardless of the frequency used.BFR conditions had a greater tendency to induce fatigue than isolated NMES.

Effects of Blood Flow Restriction Combined With Resistance Training or Neuromuscular Electrostimulation on Muscle Cross-Sectional Area.

CONTEXT: Low-load resistance training (LL) and neuromuscular electrostimulation (NES), both combined with blood flow restriction (BFR), emerge as effective strategies to maintain or increase muscle mass. It is well established that LL-BFR promotes similar increases in muscle cross-sectional area (CSA) and lower rating of perceived exertion (RPE) and pain compared with traditional resistance training protocols. On the other hand, only 2 studies with conflicting results have investigated the effects of NES-BFR on CSA, RPE, and pain. In addition, no study directly compared LL-BFR and NES-BFR. OBJECTIVE: The aim of the study was to compare the effects of LL-BFR and NES-BFR on vastus lateralis CSA, RPE, and pain. Individual response for muscle hypertrophy was also compared between protocols. DESIGN: Intrasubject longitudinal study. SETTING: University research laboratory. INTERVENTION: Fifteen healthy young males (age = 23 [5] y; weight = 77.6 [11.3] kg; height = 1.76 [0.08] m). MAIN OUTCOME MEASURES: Vastus lateralis CSA was measured through ultrasound at baseline (pre) and after 20 training sessions (post). The RPE and pain responses were obtained through modified 10-point scales, handled during all training sessions. RESULTS: Both protocols demonstrated significant increases in muscle CSA (P < .0001). However, the LL-BFR demonstrated significantly greater CSA changes compared with NES-BFR (LL-BFR = 11.2%, NES-BFR = 4.6%; P < .0001). Comparing individual increases in CSA, 12 subjects (85.7% of the sample) presented greater muscle hypertrophy for LL-BFR than for the NES-BFR protocol. In addition, LL-BFR produced significantly lower RPE and pain responses (P < .0001). CONCLUSIONS: The LL-BFR produced significantly greater increases in CSA with significant less RPE and pain than NES-BFR. In addition, LL-BFR resulted in greater individual muscle hypertrophy responses for most subjects compared with NES-BFR.

Laser Speckle Contrast Imaging for the Objective Assessment of Blood Perfusion in Keloids Treated With Dual-Wavelength Laser Therapy.

BACKGROUND: Most of the widely used methods for the assessment of keloid treatment are subjective grading scales based on the opinion of an individual clinician or patient. There is a growing need for objective methods to evaluate keloid treatment. OBJECTIVE: This study aimed to evaluate the value of laser speckle contrast imaging (LSCI) as an objective method for the assessment of dual-wavelength laser therapy for keloids. METHODS: This prospective study included 21 patients with 54 keloids. All patients were treated with a combined 585-nm pulsed dye laser and 1,064 nm neodymium-doped yttrium aluminum garnet dual-wavelength laser at 4 weeks to 6 weeks intervals. Keloids were assessed using the Vancouver Scar Scale (VSS) and LSCI. RESULTS: The total VSS score significantly decreased after 4 sessions of treatment (p < .05). Blood perfusion in keloids as measured by LSCI was significantly reduced after treatment (p < .05). The improvement of chest keloids in terms of the total VSS score and blood perfusion was significantly greater than that of scapular keloids (p < .05). There was a positive correlation between decreased perfusion and reduced total VSS score (R2 = 0.84). CONCLUSION: Blood perfusion in keloids significantly decreased after dual-wavelength laser therapy. Laser speckle contrast imaging is a promising objective method for assessing the improvement of keloids treated with laser therapy.

Measurement of total liver blood flow in intact anesthetized rats using ultrasound imaging.

This short report describes the measurement of total liver blood flow in commonly used laboratory rats using the relatively non-invasive approach of ultrasound imaging. A total of 29 rats (n = 26 Wistar-Han, n = 3 Sprague-Dawley) were imaged and both male and female rats were included. The mean (SD) total liver blood flow of all animals combined was 33.3 ± 7.8 mL/min, or 104.3 ± 17.1 mL/min/kg when normalized to observed body weight at the time of imaging. There was a trend for higher unnormalized total liver blood flow as body weight increased and the female rats had, in general, the lowest body weight and total liver blood flow of the animals studied. There were no major differences in total liver blood flow between the small number of Sprague-Dawley rats used in the study and the larger Wistar-Han group. Further research would be needed to accurately characterize any subtle differences in body weight between rats of different strains, sexes, and body weight.

Changes in Choroidal Component Ratio and Circulation After Coffee Intake in Healthy Subjects.

Purpose: The effects of coffee intake on the ratio of stromal and luminal components in the choroid and the underlying mechanism remain unclear. This prospective cross-sectional study aimed to explore how coffee intake affects the choroidal component ratio and circulation. Methods: Forty-nine right eyes of healthy adult volunteers were evaluated as the coffee intake group. Thirty-two right eyes of healthy volunteers served as the control group. The participants consumed 185 mL of coffee or water, respectively, and the systemic hemodynamics, enhanced-depth imaging optical coherence tomographic (EDI-OCT) images, and foveal mean blur rate (MBR), an indicator of blood flow velocity, were recorded at baseline and after coffee or water intake. The EDI-OCT images were binarized using ImageJ software, and subfoveal choroidal thickness (SCT) and whole, luminal, and stromal choroidal areas were calculated. Results: In the coffee intake group, significant decreases in SCT and luminal area peaked at 60 minutes after intake (both P < 0.001), whereas a significant increase in MBR peaked at 30 minutes (P < 0.001). No significant stromal area fluctuations were observed. SCT and luminal area fluctuations exhibited a significant positive correlation (r = 0.978, P < 0.001). Significant negative correlations of luminal area fluctuations with MBR fluctuations were observed by stepwise regression analysis (r = -0.220, P < 0.001). The control group exhibited no significant fluctuations. Conclusions: Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids.

Using reactive hyperemia to investigate the effect of cupping sizes of cupping therapy on skin blood flow responses.

BACKGROUND: Various cupping sizes of cupping therapy have been used in managing musculoskeletal conditions; however, the effect of cupping sizes on skin blood flow (SBF) responses is largely unknown. OBJECTIVE: The objective of this study was to compare the effect of three cupping sizes of cupping therapy on SBF responses. METHODS: Laser Doppler flowmetry (LDF) was used to measure SBF on the triceps in 12 healthy participants in this repeated measures study. Three cup sizes (35, 40 and 45 mm in diameter) were blinded to the participants and were tested at -300 mmHg for 5 minutes. Reactive hyperemic response to cupping therapy was expressed as a ratio of baseline SBF. RESULTS: All three sizes of cupping cups resulted in a significant increase in peak SBF (p< 0.001). Peak SBF of the 45 mm cup (9.41 ± 1.32 times) was significantly higher than the 35 mm cup (5.62 ± 1.42 times, p< 0.05). Total SBF of the 45 mm cup ((24.33 ± 8.72) × 103 times) was significantly higher than the 35 mm cup ((8.05 ± 1.63) × 103 times, p< 0.05). Recovery time of the 45 mm cup (287.46 ± 39.54 seconds) was significantly longer than the 35 mm cup (180.12 ± 1.42 seconds, p< 0.05). CONCLUSIONS: Our results show that all three cup sizes can significantly increase SBF. The 45 mm cup is more effective in increasing SBF compared to the 35 mm cup.

Effects of anodyne treatment on local blood flow and cutaneous sensation of the foot in a patient with peripheral neuropathy secondary to acromegaly.

Acromegaly is an excessive amount of serum growth hormone, which may present with sensorimotor polyneuropathy, affecting sensation and/or blood flow in the limbs. Symptoms include numbness, tingling or pain with impaired sensation including kinesthesia and proprioception. We report here of a 48-year-old male with a defined diagnosis of acromegaly and surgical excision of a pituitary adenoma 20 years ago. Recently he reports feet stepping on, and not feeling, objects under foot and balance problems starting 10 years ago. This study used a single-subject A-B-A design to show that behavioral changes are evident only in the presence of an intervention. Intervention consisted of Monochromatic Infrared Light Energy (MIRE), delivered by the Anodyne Therapy System (ATS). The DRT-4 laser Doppler measured red blood cell flux (flow), concentration and velocity. Levels of significance utilized the two standard deviation band method. Peripheral sensation of eight sites on each foot assessed using Semmes-Weinstein monofilaments (SWM) revealed a lack of sensation in the feet. A treatment effect as exhibited by blood flow velocity and red blood cell concentration was detected after the third week of treatment indicating peripheral dilation of the microvasculature. MIRE was an effective intervention for the treatment of acromegaly - induced polyneuropathy in this patient.

Resistance training with blood flow restriction: Impact on the muscle strength and body composition in people living with HIV/AIDS.

The aim of the study was to compare the impact of 12-week resistance training with blood flow restriction (GRTBFR) versus, traditional resistance training (GTRT) and non-training on the muscle strength and body composition HIV/AIDS participants. Muscle strength was tested at baseline, and on the 6th, 21st and 36th training sessions, using maximal repetition test. Pre- and post-intervention body composition changes were measured by dual-energy X-ray absorptiometry. Resistance training was undertaken three times a week comprising bilateral elbow extension and flexion exercises, unilateral flexion and bilateral knee extension. Changes in strength and body composition (pre- and post-intervention) between groups were evaluated by mixed models of repeated measures, and by paired and unpaired comparisons, considering the Effect Size. All groups were similar at baseline for muscle strength and body composition. Post-intervention, the training groups showed similar, statistically significant increases in muscle strength (GRTBFR=25.7-57.4%; GTRT=24.5-52.3%) and skeletal muscle tissue (GRTBFR=8.4%; GTRT=8.3%). There was also a significant change in body fat (p=0.023-0.043), with significant effect sizes for strength and skeletal muscle tissue (0.41-2.27), respectively. These results suggest that both resistance training interventions promoted muscle hypertrophy, body fat reduction and positive impact on muscle strength in people living with HIV/AIDS. Resistance training with blood flow restriction proved to be an effective alternative to include patients with marked physical weakness, unable to engage in regular strength training programme.ClinicalTrials.gov identifier: NCT02783417.

Effects of Unilateral Arm Warming or Cooling on the Modulation of Brachial Artery Shear Stress and Endothelial Function during Leg Exercise in Humans.

AIM: We examined the effect of modulating the shear stress (SS) profile using forearm warming and cooling on subsequent endothelial function in the brachial artery (BA) during exercise. METHODS: Twelve healthy young subjects immersed their right forearm in water (15 ℃ or 42 ℃) during a leg cycling exercise at 120-130 bpm for 60 min. The same exercise without water immersion served as a control. The BA diameter and blood velocity were simultaneously recorded using Doppler ultrasonography to evaluate the antegrade, retrograde, and mean shear rates (SRs, an estimate of SS) before, during, and after exercise. The endothelial function in the right BA was evaluated using flow-mediated dilation (FMD) (%) using two-dimensional high-resolution ultrasonography before (baseline) and 15 and 60 min after exercise. RESULTS: During exercise, compared with the control trial, higher antegrade and mean SRs and lower retrograde SRs were observed in the warm trial; conversely, lower antegrade and mean SRs and higher retrograde SRs were observed in the cool trial. At 15 min postexercise, no significant change was observed in the FMD from baseline in the warm (Δ%FMD: +1.6%, tendency to increase; p = 0.08) and control trials (Δ%FMD: +1.1%). However, in the cool trial, the postexercise FMD at 60 min decreased from baseline (Δ%FMD: -2.7%) and was lower than that of the warm (Δ%FMD: +1.5%) and control (Δ%FMD: +1.2%) trials. Accumulated changes in each SR during and after exercise were significantly correlated with postexercise FMD changes. CONCLUSION: Modulation of shear profiles in the BA during exercise appears to be associated with subsequent endothelial function.

Effects of Contrast Therapy Using Infrared and Cryotherapy as Compared with Contrast Bath Therapy on Blood Flow, Muscle Tone, and Pain Threshold in Young Healthy Adults.

BACKGROUND The aim of this research was to compare the effects of contrast bath therapy (CBT) and contrast therapy (CT) using infrared (IR) and cryotherapy (CR) on blood flow, muscle tone, and pain in the forearm. MATERIAL AND METHODS Twenty healthy individuals participated in this study. Each participant received 2 kinds of CT separated by a week. CBT involved immersion in hot water (38-40°C) for 4 minutes, followed by 1 minute of immersion in cold water (12-14°C) for four rotations. CT using IR and CR was performed in the same manner as CBT. RESULTS The variables measured were blood flow, muscle tone, and pain before and after intervention. Both types of CT produced fluctuations in the blood flow (P<0.05). The pain threshold increased on both therapies; a significant increase was noted with IR and CR (P<0.05) therapies. Muscle elasticity was induced and stiffness was reduced with all therapies (P<0.05). IR and CR resulted in significant changes (P<0.05) in blood flow as compared with the CBT. CONCLUSIONS The results of this study suggest that CT using IR and CR is more effective in improving blood flow than CBT and has the same effect on muscle tone and pain. Nonetheless, using IR and CR is efficient with regard to mobility and maintaining temperature; therefore, it would be convenient to use these in clinical settings. Further studies involving CT should be carried out to determine whether our findings are clinically relevant.

Acute Neuromuscular Electrical Stimulation (NMES) With Blood Flow Restriction: The Effect of Restriction Pressures.

CONTEXT: Neuromuscular electrical stimulation (NMES) combined with blood flow restriction (BFR) has been shown to improve muscular strength and size better than NMES alone. However, previous studies used varied methodologies not recommended by previous NMES or BFR research. OBJECTIVE: The present study investigated the acute effects of NMES combined with varying degrees of BFR using research-recommended procedures to enhance understanding and the clinical applicability of this combination. DESIGN: Randomized crossover. SETTING: Physiology laboratory. PARTICIPANTS: A total of 20 healthy adults (age 27 [4] y; height 177 [8] cm; body mass 77 [13] kg). INTERVENTIONS: Six sessions separated by at least 7 days. The first 2 visits served as familiarization, with the experimental conditions performed in the final 4 sessions: NMES alone, NMES 40% BFR, NMES 60% BFR, and NMES 80% BFR. MAIN OUTCOME MEASURES: Maximal voluntary isometric contraction, muscle thickness, blood pressure, heart rate, rating of perceived exertion, and pain were all recorded before and after each condition. RESULTS: The NMES 80% BFR caused greater maximal voluntary isometric contraction decline than any other condition (-38.9 [22.3] N·m, P < .01). Vastus medialis and vastus lateralis muscle thickness acutely increased after all experimental conditions (P < .05). Pain and ratings of perceived exertion were higher after NMES 80% BFR compared with all other experimental conditions (P < .05). No cardiovascular effects were observed between conditions. CONCLUSION: The NMES combined with 80% BFR caused greater acute force decrement than the other conditions. However, greater perceptual ratings of pain and ratings of perceived exertion were observed with NMES 80% BFR. These acute observations must be investigated during chronic interventions to corroborate any relationship to changes in muscle strength and size in clinical populations.

Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia.

Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO2 to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10 min. mark): escalation from 25 °C to 37 °C Phase II (10 min. mark to 15 min. mark): escalation from 37 °C to 42 °C Phase III (15 min. mark to 45 min. mark): maintenance at 42 °C Combinations of mEHT at 18 W power, mEHT at 7.5 W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 ± 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 ± 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 ± 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 °C or incubator at 37 °C, resulted in nearly identical apoptosis rates, 26 ± 4.4% and 25.9 ± 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18 W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18 W/sec), apoptosis was limited during temperature maintenance with lower power (7.5 W/sec). This presents that neither maintenance of 42 °C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.

The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice.

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical 'amplifier', which requires the metabolic support of the cochlear lateral wall. Loud sound exposure sufficient to induce permanent hearing damage causes cochlear blood flow reduction, which may contribute to hearing loss. However, sensory epithelium involvement in the cochlear blood flow regulation pathway is not fully described. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. Therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.

Acute physiological responses to combined blood flow restriction and low-level laser.

PURPOSE: Blood flow restriction (BFR) is an innovation in fitness to train muscles with low loads at low oxygen levels. Low-level laser therapy (LLLT) is a bio-energetic approach to alleviate muscle fatigue during resistance training. This study investigated the immediate effect of LLLT pre-conditioning on BFR that accelerates muscle fatigue due to ischemia. METHODS: Fifteen young adults participated in this study of a crossover randomized design. They completed a low-load contraction with various pre-conditioning (blood flow restriction with low-level laser therapy (LLLT + BFR), blood flow restriction with sham low-level laser therapy (BFR), and control). Force fluctuation dynamics, muscle oxygen saturation of hemoglobin and myoglobin (SmO2), and discharge patterns of motor units (MU) were compared. RESULTS: Normalized SmO2 during low-load contractions significantly varied with the pre-contraction protocols (Control (83.6 ± 3.0%) > LLLT + BFR (70.3 ± 2.8%) > BFR (55.4 ± 2.4%). Also, force fluctuations and MU discharge varied with the pre-contraction protocols. Multi-scale entropy and mean frequency of force fluctuations were greater in the LLLT + BFR condition (31.95 ± 0.67) than in the BFR condition (29.47 ± 0.73). The mean inter-spike interval of MUs was greater in the LLLT + BFR condition (53.32 ± 2.70 ms) than in the BFR condition (45.04 ± 1.08 ms). In particular, MUs with higher recruitment thresholds exhibited greater LLLT-related discharge complexity (LLLT + BFR (0.201 ± 0.012) > BFR (0.154 ± 0.006)). CONCLUSIONS: LLLT pre-conditioning can minimize the BFR-related decline in muscle oxygen saturation, leading to force gradation and MU discharge in a cost-effective and complex manner.

Developing a xenograft model of human vasculature in the mouse ear pinna.

Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies.

Time-of-flight resolved light field fluctuations reveal deep human tissue physiology.

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.