Skin Heating Research Articles

Cutaneous Vasodilation during Local Heating: Role of Local Cutaneous Thermosensation.

We tested the hypothesis that cutaneous vasodilation during local skin heating in humans could be manipulated based upon the ability to desensitize TRPV4 ion channels by applying the thermal stimuli in a series of pulses. Each subject was instrumented with intradermal microdialysis probes in the dorsal forearm skin and perfused with 0.9% saline at 1.5 μl/min with local skin temperature controlled with a Peltier unit (9 cm2) at 34°C. Local skin temperature was manipulated for 50 min in two classic ways: a step increase to 38°C (0.1°C/s, n = 10), and a step increase to 42°C (n = 10). To desensitize TRPV4 ion channels local skin temperature was manipulated in the following way: pulsed increase to 38°C (1 pulse per min, 30 s duration, 1.0°C/s, n = 10), and 4) pulsed increase to 42°C (1.0°C/s, n = 9). Skin blood flow (SkBF, laser Doppler) was recorded directly over the middle microdialysis probe and the dialysate from all three probes were collected during baseline (34°C) and each skin heating period. The overall cutaneous vascular conductance (CVC) response to local heating was estimated from the area under the % CVCmax-time curve. The appearance of the neuropeptide calcitonin gene related peptide (CGRP) in dialysate did not change with skin heating in any protocol. For the skin temperature challenge of 34 to 38°C, the area under the % CVCmax-time curve averaged 1196 ± 295 (SD) % CVCmax•min, which was larger than the 656 ± 282% CVCmax•min during pulsed heating (p < 0.05). For the skin temperature challenge of 34 to 42°C, the area under the % CVCmax-time curve averaged 2678 ± 458% CVCmax•min, which was larger than the 1954 ± 533% CVCmax•min during pulsed heating (p < 0.05). The area under the % CVCmax•min curve, was directly proportional to the accumulated local skin thermal stress (in °C•min) (r2 = 0.62, p < 0.05, n = 39). This association indicates a critical role of local integration of thermosensitive receptors in mediating the cutaneous vasodilator response to local skin heating. Given that we saw no differences in the levels of CGRP in dialysate, the role of the vasoactive peptide CGRP in the cutaneous vasodilator response to local skin heating is not supported by our data.

Warm hands, cold heart: progressive whole‐body cooling increases warm thermosensitivity of human hands and feet in a dose‐dependent fashion

What is the central question of this study? Investigations on inhibitory/facilitatory modulation of vision, touch and pain show that conditioning stimuli outside the receptive field of testing stimuli modulate the central processing of visual, touch and painful stimuli. We asked whether contextual modulation also exists in human temperature integration. What is the main finding and its importance? Progressive decreases in whole-body mean skin temperature (the conditioning stimulus) significantly increased local thermosensitivity to skin warming but not cooling (the testing stimuli) in a dose-dependent fashion. In resembling the central mechanisms underlying endogenous analgesia, our findings point to the existence of an endogenous thermosensory system in humans that could modulate local skin thermal sensitivity to facilitate thermal behaviour. Although inhibitory/facilitatory central modulation of vision and pain has been investigated, contextual modulation of skin temperature integration has not been explored. Hence, we tested whether progressive decreases in whole-body mean skin temperature (Tsk ; a large conditioning stimulus) alter the magnitude estimation of local warming and cooling stimuli applied to hairy and glabrous skin. On four separate occasions, eight men (27±5years old) underwent a 30min whole-body cooling protocol (water-perfused suit; temperature, 5°C), during which a quantitative thermosensory test, consisting of reporting the perceived magnitude of warming and cooling stimuli (±8°C from 30°C baseline) applied to the hand (palm/dorsum) and foot (sole/dorsum), was performed before cooling and every 10 min thereafter. The cooling protocol resulted in large progressive reductions in Tsk [10 min, -3.36°C (95% confidence interval -2.62 to -4.10); 20min, -5.21°C (-4.47 to -5.95); and 30min, -6.32°C (-5.58 to -7.05); P<0.001], with minimal changes (∼0.08°C) in rectal temperature. While thermosensitivity to local skin cooling remained unchanged (P=0.831), sensitivity to skin warming increased significantly at each level of Tsk for all skin regions [10min, +4.9% (-1.1 to +11.0); 20min, +6.1% (+0.1-12.2); and 30min, +7.9% (+1.9-13.9); P=0.009]. Linear regression indicated a 1.2%°C-1 increase in warm thermosensitivity with whole-body skin cooling. Overall, large decreases in Tsk significantly facilitated warm but not cold sensory processing of local thermal stimuli, in a dose-dependent fashion. In highlighting a novel feature of human temperature integration, these findings point to the existence of an endogenous thermosensory system that could modulate local skin thermal sensitivity in relationship to whole-body thermal states.

Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse.

Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.

Active perioperative patient warming using a self-warming blanket (BARRIER EasyWarm) is superior to passive thermal insulation: a multinational, multicenter, randomized trial

Study ObjectiveIncidence of inadvertent perioperative hypothermia is still high; therefore, present guidelines advocate “prewarming” for its prevention. Prewarming means preoperative patient skin warming, which minimizes redistribution hypothermia caused by induction of anesthesia. In this study, we compared the new self-warming BARRIER EasyWarm blanket with passive thermal insulation regarding mean perioperative patient core body temperature. DesignMultinational, multicenter randomized prospective open-label controlled trial. SettingSurgical ward, operation room, postanesthesia care unit at 4 European hospitals. PatientsA total of 246 adult patients, American Society of Anesthesiologists class I to III undergoing elective orthopedic; gynecologic; or ear, nose, and throat surgery scheduled for 30 to 120 minutes under general anesthesia. InterventionsPatients received warmed hospital cotton blankets (passive thermal insulation, control group) or BARRIER EasyWarm blanket at least 30 minutes before induction of general anesthesia and throughout the perioperative period (intervention group). MeasurementsThe primary efficacy outcome was the perioperative mean core body temperature measured by a tympanic infrared thermometer. Secondary outcomes were hypothermia incidence, change in core body temperature, length of stay in postanesthesia care unit, thermal comfort, patient satisfaction, ease of use, and adverse events related to the BARRIER EasyWarm blanket. Main ResultsThe BARRIER EasyWarm blanket significantly improved perioperative core body temperature compared with standard hospital blankets (36.5°C, SD 0.4°C, vs 36.3, SD 0.3°C; P<.001). Intraoperatively, in the intervention group, hypothermia incidence was 38% compared with 60% in the control group (P=.001). Postoperatively, the figures were 24% vs 49%, respectively (P=.001). Patients in the intervention group had significantly higher thermal comfort scores, preoperatively and postoperatively. No serious adverse effects were observed in either group. ConclusionsPerioperative use of the new self-warming blanket improves mean perioperative core body temperature, reduces the incidence of inadvertent perioperative hypothermia, and improves patients' thermal comfort during elective adult surgery.

Dairy cheese consumption ameliorates single-meal sodium-induced cutaneous microvascular dysfunction by reducing ascorbate-sensitive oxidants in healthy older adults.

Chronic dairy product intake is associated with improved cardiovascular outcomes, whereas high dietary Na impairs endothelial function through increased oxidative stress and reduced nitric oxide (NO) bioavailability. The purpose of this study was to compare the effect of acute cheese consumption with consumption of Na from non-dairy sources on microvascular function. We hypothesised that dairy cheese ingestion would augment NO-dependent vasodilation compared with Na from non-dairy sources. On five visits, fourteen subjects (61 (sem 2) years, eight male/six female) consumed either 85 g dairy cheese (560 mg Na), 85 g soya cheese (560 mg Na), 65 g pretzels (560 mg Na), 170 g dairy cheese (1120 mg Na) or 130 g pretzels (1120 mg Na). Two intradermal microdialysis fibres were inserted in the ventral forearm for delivery of lactated Ringer's solution or 10 mm-ascorbate (antioxidant) during local skin heating (approximately 50 min). Erythrocyte flux was measured continuously by laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC=LDF/mean arterial pressure) was normalised as %CVCmax (28 mm-sodium nitroprusside). Following a plateau in CVC, 15 mm-N G -nitro-l-arginine-methyl-ester was perfused to quantify NO-dependent vasodilation (approximately 45 min). NO-dependent vasodilation was greater following consumption of dairy products (560 mg Na 57 (sem 3) %) (1120 mg Na 55 (sem 5) %) compared with soya (560 mg Na 42 (sem 3) %; P=0·002) or pretzels (560 mg Na 43 (sem 4) %; P=0·004) (1120 mg Na 46 (sem 3) %; P=0·04). Ascorbate augmented NO-dependent vasodilation following intake of soya (control: 42 (sem 3) v. ascorbate: 54 (sem 3) %; P=0·01) or pretzels (560 mg Na; control: 43 (sem 4) v. ascorbate: 56 (sem 3) %; P=0·006) (1120 mg Na; control: 46 (sem 5) v. ascorbate: 56 (sem 3) %; P=0·02), but not dairy products. Na ingestion via dairy products was associated with greater NO-dependent vasodilation compared with non-dairy products, a difference that was ameliorated with ascorbate perfusion. The antioxidant properties of dairy proteins may protect against Na-induced reductions in NO-dependent dilation.

Acute Flavanol Intake Does Not Restore Attenuated Cutaneous Microvascular Function in Healthy, Young African-Americans

African Americans (AA) have increased risk for cardiovascular diseases relative to Caucasians (CA) and the underlying impairments manifest as early as the second generation prior to any overt signs of risk. We have recently demonstrated that nitric oxide dependent microvascular function in response to local heating of skin is attenuated in healthy young AA relative to CA. PURPOSE: To test the hypothesis that acute flavanol consumption restores reduced cutaneous microvascular responses to local heating in AA. METHODS: This was a double-blind crossover study To date full data sets have been collected in 7 AA and 7 CA (age: CA: 22 ± 4.0 vs. AA: 22 ± 3.6 years; BMI: CA: 23.9 ± 1.6 vs. AA: 23.7 ± 2.4 kg/m2, P>0.05 for both comparisons). Data was collected on 2 separate days (each occurred at the same time of day) separated by a minimum of 1 week. An intradermal microdialysis membrane was inserted in the forearm and skin blood flow was indexed via a laser Doppler flow probe housed within a local heater over the membrane site. After instrumentation, participants were randomly assigned to consume either a placebo or flavanol containing beverage. After recovery from the insertion trauma, the local heater was clamped at 32 °C for 45 min of baseline data collection after which the temperature was increased to 39 °C for 30 min. During 32 °C and 39 °C local heating the membrane was infused with Lactated Ringer’s Solution. Finally, maximal cutaneous vasodilation was achieved by a combination of infusion of 28 mM sodium nitroprusside and 43 °C local heating. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flux/mean arterial pressure and normalized as % maximal CVC (%CVCmax). RESULTS: CVC was similar between groups at 32 °C (Placebo: AA, 8 ± 4 vs. CA, 10 ± 3 % max, P=0.40; Flavanol: AA: 8 ± 5 vs. 11 ± 4 % max, P=0.26). CVC at 39 °C was reduced in AA (Placebo: AA, 40 ± 11 vs. CA: 59 ± 14 % max; P=0.01; Flavanol: AA, 33 ± 16 vs. 53 ± 12 % max; P=0.02); however, there was no effect between treatments (P>0.05 for interaction). CONCLUSION: These data suggest that AA have reduced cutaneous vascular responses to local heating; however this response is not effected by acute flavanol supplementation. This project was supported by institutional start-up funds provided to R. Matthew Brothers from The University of Texas at Austin.

Acute Cheese Consumption Ameliorates Sodium-Induced Cutaneous Microvascular Dysfunction by Reducing Ascorbate-Sensitive Oxidants

In epidemiological studies, chronic dairy intake is associated with improved cardiovascular outcomes; conversely, high dietary sodium (Na) consumption impairs endothelial function through increased oxidative stress and reduced nitric oxide (NO)-dependent mechanisms. PURPOSE: To examine if the high Na in cheese has a less negative effect on microvascular dysfunction relative to equivalent Na from non-dairy sources due to the actions of milk-based macronutrients and proteins. We hypothesized that 1) acute dairy based cheese ingestion augments NO-dependent vasodilation (VD) compared to an equal amount of Na from non-dairy sources, and 2) the Na-induced decrease in NO-dependent VD is mediated by oxidant stress mechanisms. METHODS: On 5 separate visits, 14 subjects (61±2 yrs) consumed either 85 g cheddar cheese (560 mg Na), 85 g soy cheese (560 mg Na), 65 g pretzels (560 mg Na), 170 g cheddar cheese (1120 mg Na), or 130 g pretzels (1120 mg Na). Two intradermal microdialysis fibers were inserted in the forearm skin for local delivery of 1) lactated Ringer’s solution (control site) and 2) ascorbate (antioxidant site). Red blood cell flux was measured by laser-Doppler flowmetry (LDF) during local skin heating (42°C) to induce endothelial NO synthase-dependent VD. Once a plateau in cutaneous vascular conductance (CVC = LDF/MAP) occurred, 20 mM L-NAME was perfused at both sites to directly quantify NO-dependent VD. Data were expressed as a percentage of maximum (%CVCmax; 28mM SNP). RESULTS: The total vasodilatory response was not different among the five dietary treatments. NO-dependent VD was higher following dairy cheese consumption compared to a Na-equivalent in soy cheese (59±5 vs. 44±6%; p=0.03) or pretzels (560 mg Na: 59±5 vs. 45±4%; p=0.03, 1120 mg Na: 57±4 vs. 46±5%; p=0.02). Local ascorbate administration abolished these differences (no main dietary treatment effect). CONCLUSION: Na ingestion in cheese was associated with a higher NO-dependent VD compared to an equal amount of non-dairy Na, a difference that was abolished with a local non-specific antioxidant. These data suggest that macronutrients in dairy based cheese may protect against acute Na-induced microvascular dysfunction through antioxidant mechanisms. Supported by Dairy Management Inc.

Endothelin‐B Receptor Responses in Young and Postmenopausal Women

Cardiovascular disease (CVD) is the leading cause of the death in women, and postmenopausal women (PMW) are at an increased risk for developing CVD. Endothelin‐1 (ET‐1) contributes to age‐related endothelial dysfunction in men via the ETA receptor. However, there are sex differences in ET‐1 regulation of vascular function, and ETB receptors are influenced by fluctuations in ovarian hormones.PURPOSEThe purpose of this study was to test the hypothesis that ETB receptors contribute to impaired microvascular function in PMW.METHODSWe measured skin blood flow (SkBF) in 11 young women (YW; 22±1 years, 22±1 kg/m2) and 10 PMW (58±2 years, 24±1 kg/m2) using laser Doppler flowmetry during microdialysis perfusions of lactated Ringer's (control), an ETB receptor antagonist (BQ‐788, 300nM), and an ETA receptor antagonist (BQ‐123, 500 nM). We utilized local skin heating (42°C) to induce microvascular vasodilation, followed by perfusion of sodium nitroprusside (28mM) to elicit maximal dilation. Mean arterial blood pressure (MAP) was measured throughout. Cutaneous vascular conductance (CVC) was calculated as SkBF/MAP during the plateau established during local heating, and expressed as a percent of maximal dilation. Unpaired t‐tests were used to compare variables between YW and PMW.RESULTSResting MAP was higher in PMW (93±2 mmHg) compared to YW (80±2 mmHg; P&lt;0.05). Vasodilatory responses to local heating (control site) tended to be lower in PMW (YW: 91±2 vs. PMW: 81±5 CVC % max; P=0.12). ETB receptor blockade tended to decrease cutaneous vasodilation in YW (control: 91±2 vs. BQ‐788: 85±3 CVC % max; P=0.08), but tended to enhanced vasodilation in PMW (control: 81±5 vs. BQ‐788: 92±1 CVC % max; P=0.08). ETA receptor blockade had minimal effect in YW (control: 91±2 vs. BQ‐123: 92±2 CVC % max; P=0.35), but tended to increase cutaneous vasodilation in PMW (control: 81±5 vs. BQ‐123: 90±2 CVC % max; P=0.11).CONCLUSIONETB receptors appear to mediate vasodilation in YW. However, microvascular vasodilation is blunted in PMW, possibly due to greater ETB and ETA mediated vasoconstriction.Support or Funding InformationSupported by NIH Grant U54 GM 104941 01A1 and University of Delaware Research Foundation.

The vasomotor symptoms and skin changes in natural menopause among Iranian women

Introduction: Menopause is the most important event in middle-age. Women, in this period, face several changes. Vasomotor symptoms and skin changes are prevalent in the middle-age. This study, mainly, was performed identifying the vasomotor symptoms and skin changes in menopausal women. Materials and methods: Study sample was consisted of 150 women who have visited the healthcare centers, experienced natural menopause as discontinuity of menstrual at least for 12-monthes. They have been selected randomly. Survey instruments were structured questionnaire, informational records, symptoms and signs checklist, centi-meter and balance and the data collecting method was through interview, observation, and examination. The data were analyzed using logistic regression. Results: According to study results, skin warming and hotness (55.3%), hands and legs nipping (63.3%), hirsutism of pinion lip (27.3%), reduction of armpit hair (38%), acne (12%), Skin extenuation and wrinkling (51.3%) were reported. The most important point of the study is the significant relationship between amount of tea consumption and flushing severity (P=0.008, OR=3.18). Also, there was a significant relation between education and menopause duration, sleep disorders and severity of flushing, menopause duration and skin collagen reduction (P<0.05). Conclusion: Skin and vasomotor changes is prevalent in these women. Flushing severity influenced by tea consumption, such that drinking more tea will decrease the flushing, is the start point of more researches in this field.

The effect of heating rate on the cutaneous vasomotion responses of forearm and leg skin in humans

We examined skin blood flow (SkBF) and vasomotion in the forearm and leg using laser-Doppler fluxmetry (LDF) and spectral analysis to investigate endothelial, sympathetic, and myogenic activities in response to slow (0.1°C·10s−1) and fast (0.5°C·10s−1) local heating. At 33°C (thermoneutral) endothelial activity was higher in the legs than the forearms (P≤0.02). Fast-heating increased SkBF more than slow heating (P=0.037 forearm; P=0.002 leg). At onset of 42°C, endothelial (P=0.043 forearm; P=0.48 leg) activity increased in both regions during the fast-heating protocol. Following prolonged heating (42°C) endothelial activity was higher in both the forearm (P=0.002) and leg (P<0.001) following fast-heating. These results confirm regional differences in the response to local heating and suggest that the greater increase in SkBF in response to fast local heating is initially due to increased endothelial and sympathetic activity. Furthermore, with sustained local skin heating, greater vasodilatation was observed with fast heating compared to slow heating. These data indicate that this difference is due to greater endothelial activity following fast heating compared to slow heating, suggesting that the rate of skin heating may alter the mechanisms contributing to cutaneous vasodilatation.

Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR)

Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5–10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).

The contribution of sensory nerves to the onset threshold for cutaneous vasodilatation during gradual local skin heating of the forearm and leg

During local skin heating, the temporal onset of vasodilatation is delayed in the leg compared to the forearm, and sensory nerve blockade abolishes these differences. However, previous work using rapid skin heating did not allow for determination of sensory nerve influences on temperature thresholds for vasodilatation. Two sites were examined on both the forearm and leg, one control (CTRL), and one treated for sensory nerve blockade (EMLA). Skin blood flux was monitored using laser-Doppler probes, with heaters controlling local skin temperature (Tloc). Tloc was increased from 32–44°C (+1°C·10min−1). Stimulus–response curves were constructed by fitting a four-parameter logistic function. EMLA significantly increased Tloc onset in the forearm (CTRL=35.3±0.4°C; EMLA=36.8±0.7°C) and leg (CTRL=36.5±0.4°C; EMLA=38.4±0.5°C; both P<0.05). At both CTRL and EMLA, Tloc onset was higher in the leg compared to the forearm (both P<0.05). In the forearm, median effective temperature to elicit 50% vasodilatation (ET50) was similar between sites (CTRL=39.7±0.3°C; EMLA=40.2±0.4°C; P=0.09); however, in the leg, EMLA significantly increased ET50 (CTRL=40.2±0.3°C; EMLA=41.0±0.3°C)(P<0.05). At CTRL sites, no limb difference was observed for ET50 (P=0.06); however, with EMLA, ET50 was significantly higher in the leg (P<0.05). EMLA significantly increased the gain of the slope at the forearm, (CTRL=0.31±0.01%CVCmax·°C−1; EMLA=0.45±0.07%CVCmax·°C−1), and leg (CTRL=0.37±0.05%CVCmax·°C−1; EMLA=0.54±0.04%CVCmax·°C−1)(both P<0.05). At CTRL sites, the gain was significantly higher in the leg (P<0.05); however, for EMLA, no significant limb difference existed (P=0.10). These data indicate that the onset of vasodilatation occurs at a lower temperature in the forearm than the legs, and sensory nerves play an important role in both limbs.

CO-04: Aging altered epoxyeicosatrienoic acid-mediated regulation of peripheral conduit artery diameter at rest and during sustained flow-mediated dilatation

Background We evaluated the evolution of NO and CYP450 epoxygenases-derived epoxyeicosatrienoic acids (EETs) availability in conduit arteries during aging. Methods Radial artery diameter and mean wall shear stress were determined in 83 subjects (19 to 71 years old) at rest and during sustained endothelium-dependent flow-mediated dilatation induced by hand skin heating. The role of EETs and NO was assessed using the brachial infusion of inhibitors of cytochrome P450 epoxygenases (fluconazole) and NO-synthase (L-NMMA). Results Aging increased the reduction in basal arterial diameter induced by L-NMMA and nitrite plasma levels, an indicator of NO bioavailability. At the opposite, aging decreased EETs plasma levels and tended to reduce the basal vasoconstriction induced by fluconazole. Moreover, aging blunted the synergistic vasoconstricting effect of L-NMMA+fluconazole. Furthermore, the magnitude of flow-mediated dilatation was independently and negativelyrelated with age, together with baseline diameter and systolic blood pressure, and positively correlated with shear stress variation during heating. The increase in local nitrite level during heating and the decrease in flow-mediated dilatation induced by L-NMMA were not affected by aging. In contrast, aging tended to reduce the release of EETs and reduced the inhibitory effect of fluconazole alone and combined with L-NMMA on flow-mediated dilatation. Conclusions These results show that aging primarily impairs EETs availability and alters NO/EETs balance, contributing to promote endothelial dysfunction at the level of peripheral conduit arteries.

Effect of Preoperative Forced-Air Warming on Hypothermia in Elderly Patients Undergoing Transurethral Resection of the Prostate.

Elderly patients under spinal anesthesia are vulnerable to hypothermia, leading to increased morbidity. The aim of this study was to investigate the effects of preoperative forced-air warming on perioperative hypothermia and shivering in elderly patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia. Patients (> 65-year-old) scheduled for TURP under spinal anesthesia were randomly assigned to receive preoperative forced-air skin warming for 20 min (the pre-warmed group, n = 25) or not (control group, n = 25). Core temperatures were measured at 15-min intervals after spinal anesthesia, and intra- and post-operative shivering were also assessed. Incidences of intraoperative hypothermia (< 36 ºC) in the pre-warmed and control groups were not significantly different (10/25 [40%] vs. 15/24 [62.5%], P = .259). However, severities of hypothermia were significantly different (P = .019). No patient in the pre-warmed group showed moderate or profound hypothermia, whereas of patients in control group 21% and 13% did so, respectively. This study demonstrated that a brief period of preoperative forced-air warming did not completely prevent intraoperative hypothermia or shivering, but it could significantly reduce its severity in elderly male patients under spinal anesthesia.

Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study.

The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities. A total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment. A total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6°C. The median maximum temperature during the 1-hour incubation period was 41.2°C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period. Warming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice.

Skin temperature reveals the intensity of acute stress

Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term drop in skin temperature in homeotherms. We tested, for the first time, whether this response has the potential to quantify stress, by exhibiting proportionality with stressor intensity. We used established behavioural and hormonal markers: activity level and corticosterone level, to validate a mild and more severe form of an acute restraint stressor in hens (Gallus gallus domesticus). We then used infrared thermography (IRT) to non-invasively collect continuous temperature measurements following exposure to these two intensities of acute handling stress. In the comb and wattle, two skin regions with a known thermoregulatory role, stressor intensity predicted the extent of initial skin cooling, and also the occurrence of a more delayed skin warming, providing two opportunities to quantify stress. With the present, cost-effective availability of IRT technology, this non-invasive and continuous method of stress assessment in unrestrained animals has the potential to become common practice in pure and applied research.

The contribution of sensory nerves to cutaneous vasodilatation of the forearm and leg to local skin warming

The initial cutaneous vasodilatory response to local skin heating is greater in the forearm than in the leg (1). While the initial vasodilatation of the forearm in response to local heating is primarily dependent on sensory nerves (2), their role in the leg is unknown. We compared the contribution of sensory nerves in regulating the cutaneous vasodilatory response of the forearm and leg to local heating using a local anaesthetic (EMLA) cream.

Millimeter waves as a source of selective heating of skin.

This study demonstrates that 20-100 GHz range can be used for spatially-accurate focusing of heating inside the skin achieved by varying frequency and exposure beam size, as well as by enforcing air convection. The latter is also used to reduce overheating of skin surface. Heating at different skin depths depending on these parameters is investigated in detail using the hybrid bio-heat equation. In particular, it is shown that decreasing frequency and/or increasing exposure beam size at forced airflow result in elevation of heating of deeper layers of tissue and decrease of skin surface temperature. Changes of water content within 15%, which exceed those due to aging and presence of tumors, only slightly affect heating. Exposure intensity necessary to reach a target temperature significantly increases in different areas of body with elevated blood flow. Dependence on exposure intensity and hyperthermia treatment duration is also investigated and discussed. Results of this study suggest that the lower part of the millimeter-wave range is an attractive alternative for non-invasive thermal treatment of skin cancer with a high spatial resolution.

Combined facial heating and inhalation of hot air do not alter thermoeffector responses in humans.

The influence of thermoreceptors in human facial skin on thermoeffector responses is equivocal; furthermore, the presence of thermoreceptors in the respiratory tract and their involvement in thermal homeostasis has not been elucidated. This study tested the hypothesis that hot air directed on the face and inhaled during whole body passive heat stress elicits an earlier onset and greater sensitivity of cutaneous vasodilation and sweating than that directed on an equal skin surface area away from the face. Six men and two women completed two trials separated by ∼1 wk. Participants were passively heated (water-perfused suit; core temperature increase ∼0.9°C) while hot air was directed on either the face or on the lower leg (counterbalanced). Skin blood flux (laser-Doppler flowmetry) and local sweat rate (capacitance hygrometry) were measured at the chest and one forearm. During hot-air heating, local temperatures of the cheek and leg were 38.4 ± 0.8°C and 38.8 ± 0.6°C, respectively (P = 0.18). Breathing hot air combined with facial heating did not affect mean body temperature onsets (P = 0.97 and 0.27 for arm and chest sites, respectively) or slopes of cutaneous vasodilation (P = 0.49 and 0.43 for arm and chest sites, respectively), or the onsets (P = 0.89 and 0.94 for arm and chest sites, respectively), or slopes of sweating (P = 0.48 and 0.65 for arm and chest sites, respectively). Based on these findings, respiratory tract thermoreceptors, if present in humans, and selective facial skin heating do not modulate thermoeffector responses during passive heat stress.

Local Skin Warming Enhances Color Duplex Imaging of Cutaneous Perforators

The perforator flap is one of the most useful techniques in reconstructive surgery. The operative procedure for these flaps will be greatly simplified if accurate localization of the course of the perforator can be preoperatively confirmed. However, small vessels with diameters less than 0.5 mm cannot be readily traced with conventional imaging techniques. Local skin warming temporarily increases cutaneous blood flow and vasodilation. In this study, we established a local skin warming procedure, and performed this before color duplex imaging to improve preoperative perforator mapping and enable precise flap design.