Local and central sympathetic reflex control of blood flow in skeletal muscle and subcutaneous tissue in normal man

Summary. The effect of age and sex on relative changes in blood flow and vascular resistance in skeletal muscle and subcutaneous tissue during postural changes and during local increase in transmural pressure was studied in 33 healthy subjects. The intra-individual variation was studied in five subjects. Blood flow was measured by the local ¹³³Xenon wash-out method. No relation to age or sex was seen in the centrally elicited sympathetic vasoconstrictor responses in subcutaneous tissue and skeletal muscle and in the locally elicited vasoconstriction in subcutaneous tissue. A small, but statistically significant, correlation to sex and age was found in the local sympathetic vasoconstrictor response in skeletal muscle. The age correlation was caused only by an attenuated response in the young subjects below 40 years of age and may be fortuitous. The intra-individual variation was acceptably small. Based on the present results, a reduction in blood flow in skeletal muscle and subcutaneous tissue during centrally or locally elicited sympathetic vasoconstriction of 10% or less should be considered abnormal. The local ¹³³Xenon wash-out method is of value in examining patients suspected of dysfunction in the sympathetic part of the autonomic nervous system.     

Local skin blood flow in hypokinesis

Functional indices of peripheral autonomic nervous system responsible for regulation of tissue circulation were studied with doppler laser-flowmetry in patients exposed to long-term hypokinesia. Valsalva test, orthostatic test, cold test, etc., have discovered shifts in the system regulating local skin blood flow. Compared to control, changes in the blood flow were considerable and its recovery went very slowly.     

The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD)

Abstract. Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers ( n =16), LDF under control conditions demonstrated an increase in skin blood flow at stage I ( P <0.01). A decrease in skin blood flow under control conditions was seen at stages II ( P <0.05) and III ( P <0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome. Digital systolic blood pressures were increased at stages II ( P <0.05) and III ( p <0.001). These findings indicate that abnormalities in skin blood flow, as observed in RSD patients, are of microcirculatory origin. The observed decrease in skin blood flow at stages II and III most likely results from functional vasospasm rather than from structural vessel wall changes.     

Laser Doppler measurements of skin blood flow before,during, and after lumbar sympathetic blockade in children and young adults with reflex sympathetic dystrophy syndrome

Changes in the skin capillary blood flow (SBF) and temperature before, during, and 1 hour after unilateral lumbar paravertebral sympathetic blockade (LSB) were studied simultaneously with laser Doppler flowmetry and thermometry in patients with reflex sympathetic dystrophy syndrome. The baseline flow measurements in the toes on the affected limb were significantly lower than in the contralateral limb (p<0.01). During LSB, a 10-fold increase in SBF was detected within 4 minutes after injection of a local anesthetic agent when the sympathetic blockade was effective; an increase of more than 1°C in the skin temperature occurred within 11 minutes. Measurements 1 hour after blockade showed an 18-fold (mean) increase in SBF in the toes (p<0.0001) and a 2-fold (mean) increase in SBF in the thighs (p<0.001). There was a significant decrease in the skin blood flow in the contralateral toes after the sympathetic blockade (p<0.01). We conclude that laser Doppler flow measurements can be used to detect immediate onset of sympathetic blockade in patients under general anesthetic or conscious sedation.     

Dynamics of skin blood flow in human sepsis

Objective The study was undertaken to determine if sepsis alters the pattern of vasomotion and reactive hyperaemia in the skin.Design This was a prospective, observational study.Setting: The study was performed in the medical and surgical intensive care units of a tertiary referral hospital.Patients and participants 11 patients with sepsis (using Bone's criteria [1]), were compared with 19 patients recovering from coronary artery bypass grafting who were used as non-septic controls. Nineteen normal volunteers were also studied.Measurements and results Skin blood flow was measured on the forearm using laser Doppler flowmetry at rest and after 2 min arterial occlusion with a tourniquet. The resting blood signal was analyzed by calculating the mean skin blood flow, the power of the skin blood flow signal (variance) and the power spectrum. The rate of recovery after arterial occlusion was determined by calculating the peak increase in skin blood flow and the time constant of the decay of skin hyperaemia back to baseline flow. Patients with sepsis had a mean skin blood flow of 6.24 (3.48) ml min^–1 per 100 g tissue compared with 4.35 (1.41) ml min^–1 per 100 g tissue for the patients after coronary artery bypass grafting (p<0.05). The septic patients also showed a marked increase in the fraction of total power in the 0.1–0.15 Hz frequency band (0.19 (0.17) versus 0.068 (0.033),p<0.05), a decreased peak hyperaemic response (40 (23)% increase in flow above baseline after cuff release versus 147 (19)% and a prolonged time constant for recovery from hyperaemia (22.8 (12.7) versus 11.7 (8.5) seconds,p<0.05). These results imply an increased local rather than central control of skin blood flow.Conclusion The laser Doppler flowmeter allows local rather than global haemodynamics to be studied. Abnormalities of skin blood flow control are found in sepsis, and this technique may prove useful to monitor the effects of treatment, especially if the use of laser Doppler flowmetry can be extended to other organs at risk of damage during sepsis such as gastro-intestinal mucosa.     

Ultrasound treatment of reflex sympathetic dystrophy

Three cases of lower extremity reflex sympathetic dystrophy (RSD) responded dramatically to a daily low dose ultrasound (0.5 watts/cm2 X 5 minutes) therapy to the tarsal tunnel and plantar nerve distribution, and the use of a shoe insert. Two of the three cases had been refractory to more standard therapy for RSD, including pharmacologic agents. All three patients preferred a conservative approach to surgical sympathectomy. No complications were observed, and all three cases are now symptom free. Daily ultrasound treatments are time-consuming and costly but are safe and may be useful for patients who refuse surgical sympathectomy. We hypothesize that ultrasound may have affected peripheral sympathetic nerve fibers. However, more indirect effects of ultrasound, such as increased blood flow to the limb, may be part of the action mechanism as well.     

Treatment of reflex sympathetic dystrophy with topical capsaicin. Case report.

A 31-year-old woman with intractable reflex sympathetic dystrophy experienced nearly complete, though temporary, resolution of pain following 3 weeks of topical capsaicin. We propose that capsaicin may be a useful treatment for reflex sympathetic dystrophy, either by depleting substance P from primary afferent neurons that mediate allodynia, or by modulating sympathetic efferent activity.     

Effect of indirect heating on the postural control of skin blood flow in the human foot

It has been shown in previous studies that skin blood flow in the human foot falls when the extremity is placed below heart level, owing to an increase in precapillary resistance that is probably mediated by a local sympathetic axon reflex or a myogenic response. In order to clarify the influence of the central thermoregulatory mechanisms on this local postural vasoconstrictor response, 12 normal male subjects were studied under standardized conditions, at rest and during heating of the trunk with an electric blanket. Skin blood flow was measured before and during body heating using laser Doppler flowmetry with the foot maintained at heart level and placed passively 50 cm below the heart. Skin blood flow and skin temperature were determined at two sites: the plantar surface of the big toe, an area with a relatively large number of arteriovenous anastomoses, and the dorsum of the same foot, where these anastomoses are few or absent. When the foot was placed in the dependent position, skin blood flow recorded in the dorsum of the foot during indirect heating fell to a level similar to that achieved before heating. In contrast, indirect heating greatly diminished the postural fall in skin blood flow recorded in the plantar surface of the big toe. In conclusion, the partial release of sympathetic vasoconstrictor tone associated with indirect heating appears to over-ride the local postural control of cutaneous vascular tone in areas where arteriovenous anastomoses are relatively numerous.     

Sympathetic reflex control of subcutaneous blood flow in patients with congestive heart failure

Central and local regulation of forearm subcutaneous vascular resistance (FSVR) during postural changes were studied in congestive heart failure (CHF). Blood flow was measured by the local 133Xe-washout technique. Nine patients with severe CHF (baseline angiographic ejection fraction, 23 +/- 2%, mean +/- SEM; cardiac index, 2.2 +/- 0.2 litres min-1 m-2; increased left ventricular pressures and dimensions) were compared with seven control subjects who had normal cardiac performance. Baseline FSVR and plasma concentrations of noradrenaline and adrenaline were substantially higher in patients with CHF than control subjects. However, the patients, like control subjects, increased FSVR by 46 +/- 3% in response to increase in local venous transmural pressure and disclosed a normal response to decrease in forearm perfusion pressure. Both responses to changes in vascular transmural pressure were preserved after either proximal nervous blockade or local beta-receptor blockade. Central sympathetic stimulation was induced with use of 45 degrees upright tilt. Control subjects developed vasoconstriction (FSVR increased by 59 +/- 5%), which was completely abolished after proximal nerve blockade. Patients with CHF developed vasodilatation (FSVR decreased by 24 +/- 8%), which was not only abolished but reversed after proximal nerve blockade (FSVR increased by 22 +/- 7%), probably owing to the increased humoral vasoconstrictor activity. The paradoxical vasodilator response to central sympathetic stimulation in these patients was reversed after local beta-receptor blockade (FSVR increased by 19 +/- 9%). The local vasoconstrictor reflex responsiveness and intrinsic vascular reactivity were not affected by the augmented baseline sympathetic vasoconstrictor activity in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential time courses of skin blood flow and hyperalgesia in the human sunburn reaction following ultraviolet irradiation of the skin.

The response of skin to ultraviolet (UV) irradiation is an inflammation with pronounced vasodilation and hyperalgesia. Volunteers underwent UV irradiation of patches of forearm skin 3 cm in diameter. The intensity of the UV irradiation (290-320 nm) ranged between 133 mJ/cm2 and 400 mJ/cm2. Changes in skin blood flow were measured with laser Doppler technique at 3, 6, 9, 12, 24, 30, 36, 48, 60, 72, 96 and 216 h post UV irradiation. The alteration in pain threshold was measured for heat with a Peltier thermode and for pressure with a metal stylus. The effect of repeated topical pre-treatment 4 days prior to UV irradiation with 1.5 g of 0.04% capsaicin containing ointment was also investigated.UV irradiation resulted in a dose-dependent increase of skin blood flow for more than 96 h post-irradiation. There were two peaks of blood flow at 12 h and 36 h. Topical application of capsaicin prior to UV irradiation attenuated blood flow from 30 h to 45 h post UV irradiation. Enhanced blood flow was also present 5 mm outside the irradiated area (flare reaction). The control level of heat pain threshold was 44.5+/-0.7;C in normal skin. Heat pain thresholds were lowered by up to 7.761.2;C in UV-irradiated areas in a dose-dependent fashion. The control level of pressure pain threshold was 15.260.3N. Pressure pain thresholds were lowered by up to 6 N in irradiated areas. Maximal hyperalgesia coincided with the second peak of skin blood flow between 30 h and 60 h post UV irradiation. The effects of topical application of capsaicin suggests an involvement of neuropeptide mechanisms in the late phase of the human sunburn reaction.     

Familial high serum PICP: high even in skin interstitial fluid, suppressible by topical corticosteroid treatment.

Circulating C-terminal propeptide of type I procollagen (PICP), mostly originating from bone, is mainly cleared by mannose receptors (MRs) in liver endothelial cells (LECs). We hypothesized that skin macrophage MRs could also play a role in local (in situ) clearance of PICP originating from skin type I procollagen synthesis. We tested this hypothesis in a male subject with a genetic systemic clearance defect, apparently due to an abnormality in MR function in LECs (or in PICP structure). Since skin macrophages may express the same MRs as LECs do, the genetic defect could affect them as well; hence, if elevated PICP concentrations even in skin interstitial fluid (IF) were found in our subject, it would suggest a role for local MR-mediated PICP clearance in skin. Since glucocorticoids (GCs) upregulate MRs in vitro, we measured the effect of topical GC on suction blister fluid (SBF)-PICP of the test person as compared with normal subjects. SBF-PICP was elevated in the case, which was consistent with the hypothesis. Furthermore, the GC-induced decrease was accentuated. The results suggest that skin macrophage MRs can have a role in skin PICP clearance in situ.     

Topical corticosteroid inhibits autoregulation of cutaneous blood flow

In eight healthy persons, the skin-fold between the thumb and the forefinger was treated with a potent corticosteroid under occlusive dressings. Before treatment and following 10, 24, 48 and 72 h of steroid application, cutaneous autoregulation of blood flow and reactive hyperaemia were measured by means of the atraumatic epicutaneous 133Xe washout technique. Using the outer 2 mm of the skin-fold, and shielding the rest of the hand with a lead plate, cutaneous blood flow rate could be monitored separately. After 10 h of treatment, autoregulation of blood flow was almost unaffected, but after 24 h of treatment and during the following 2 days, the autoregulatory response exhibited a significant reduction, which correlated to steroid application time. Reactive hyperaemia demonstrated a clear, but insignificant, reduction at 10 h of treatment; however during the following 48 h, maximal post-occlusive blood flow rate was significantly reduced. Placebo did not affect either autoregulation of blood flow or reactive hyperaemia.     

Sympathetic blockade and amitriptyline in the treatment of reflex sympathetic dystrophy

We prospectively investigated the outcome of a combination therapy of oral amitriptyline and sympathetic ganglion blockade on 10 patients suffering from reflex sympathetic dystrophy of the upper extremity for at least three months. The efficacy of the treatment was evaluated by clinical examination, pain ratings on the visual analogue scale (VAS) and grip strength measurements using the Jamar dynamometer. The results were statistically analysed with Wilcoxon signed-ranks test for comparison of the before and after treatment grip strength measurements and with paired t-test for comparison of the mean of initial and consecutive pain ratings on the VAS. Values of p < 0.01 were considered to be statistically significant. Combination therapy proved beneficial in this particular patient population, which, as far as previously documented studies are concerned, would otherwise respond less favourably to a treatment consisting solely of sympathetic blockade.     

Sicorten: a synthetic corticosteroid for topical treatment of common dermatoses

In an open non-comparative trial 247 eczema patients were treated with Sicorten topicals. Sicorten cream yielded good to very good results in 90%, 97% and 100% of the patients suffering from atopic dermatitis, contact dermatitis and seborrhoeic dermatitis, respectively, while Sicorten ointment produced similar results in 97% and 100% of the patients with chronic atopic dermatitis and chronic contact dermatitis, respectively. In a double-blind trial involving 108 patients suffering from atopic, seborrhoeic or contact dermatitis, the therapeutic effect of Sicorten and Betnelan creams and ointments was not significantly different.     

Effect of topical antimicrobial treatment on aerobic bacteria in the stratum corneum of human skin.

The efficacy of antimicrobial agents applied topically to the skin surface in eradicating coagulase-negative staphylococci (CNS) residing in the stratum corneum underlying the surface was examined. Glabrous skin was sampled with a 26-cm2 contact plate containing Trypticase soy agar. Five antiseptic solutions and four antimicrobial ointments were evaluated. The antiseptic solutions (10% povidone-iodine, 2% aqueous iodine, 2% tincture of iodine, 70% ethanol, and 0.5% chlorhexidine-ethanol) were applied for 15 s with a gauze sponge. The antimicrobial ointments (iodophor, silver sulfadiazine, mupirocin, and a triple-antibiotic ointment containing neomycin, polymyxin, and bacitracin) were applied and covered for 6 h with gauze. After treatment, the surface was sampled, 15 to 25 keratinized layers were subsequently removed by sequential stripping with cellophane tape, and the stratum corneum was sampled. All agents were effective in eradicating CNS from the surface (80 of 88 trials). However, only 2% iodine (17 of 20 trials), iodophor (8 of 12), mupirocin (6 of 10), and the triple-antibiotic ointment (9 of 11) eradicated CNS from the stratum corneum reliably (greater than or equal to 50% of trials). The stratum corneum was repopulated with resident flora within 24 h of treatment with 2% iodine (4 of 4 trials), iodophor (6 of 7), or mupirocin (5 of 6), but repopulation occurred in only 1 of 7 trials with the triple-antibiotic ointment. Topical treatment of skin with antimicrobial agents usually eradicates CNS from the skin surface but may not eradicate CNS from the stratum corneum. Only the triple-antibiotic ointment eradicated CNS from the stratum corneum and prevented repopulation with resident flora.     

Microvascular blood flow and skin temperature changes in the fingers following a deep nspiratory gasp

The aims of this study were to quantify the changes in finger pulp skin temperature, laser Doppler flow (LDF, microvascular flux) and photoplethysmogram (PPG, microvascular blood volume pulsatility), induced by a deep inspiration in healthy subjects, and to investigate the repeatability of these responses within a measurement session and between measurement sessions on separate days. A system comprising an electronic thermometer, a laser Doppler flowmeter and a PPG amplifier measured simultaneous vasoconstrictor responses to a deep inspiratory gasp from three adjacent fingers of one hand. Clearly defined responses were obtained in 15 of the 17 subjects studied. Skin temperature fell in all of these subjects after each gasp, with a median fall of 0.089 degrees C (P < 0.001). The median value of LDF flux reduction was 93% (P < 0.001) indicating a momentary almost complete shut-down of microvascular blood flow; and PPG also showed a large response relative to pulse amplitude of 2.6 (P < 0.001). The median times for waveforms to reach their minimum were 4.6 s (PPG), 6.3 s (LDF) and 29.1 s (skin pulp temperature), with median delays between minima of LDF and PPG of 1.6 s (P < 0.001) and skin temperature and PPG of 23.5 s (P < 0.001). The vascular responses of skin temperature, LDF and PPG to an inspiratory gasp were repeatable, with temperature change repeatable to within 10% of the median subject change.