Changes In Cutaneous Blood Flow Research Articles

Cutaneous blood flow increases in the rat hindpaw during dorsal column stimulation

The purpose of this study was to determine the optimal stimulation site and parameters that result in the greatest changes in cutaneous blood flow during dorsal column stimulation (DCS). Laser Doppler flowmetry was used to assess cutaneous blood flow changes in both rat hindpaws during DCS with a unipolar ball electrode. We found that stimulating the dorsal column at the L 2 spinal segment at 0.6 mA at either 25 or 50 Hz with a pulse duration of 0.2 ms resulted in the largest cutaneous blood flow increases in the rat hindpaw. In addition, the DCS response appeared to be limited primarily to the hindpaw ipsilateral to the site of DCS.

Micro- and macrocirculatory, and biohumoral changes after a month of physical exercise in patients with intermittent claudication

We studied 15 subjects with intermittent claudication, classed as stage II according to Leriche-Fontaine. The patients were subjected to laser Doppler flowmetry, strain gauge plethysmography, Doppler velocimetry, and blood sampling, in basal conditions and after one month of physical training. Symptom-free walking distance at the end of the training period showed a significant increase, while there was no major change in maximal walking distance or the Windsor index. Laser Doppler flowmetry showed no significant change in cutaneous blood flow at rest, after the month of physical training. On the other hand, strain gauge plethysmography showed a significant decrease in rest flow at the end of the training period, while peak flow of postischemic hyperemia did not change appreciably. Biohumoral evaluations showed a significant decrease of white blood cell count, triglycerides and uric acid. Platelet count, prothrombin time, aPTT and plasminogen were unchanged. On the other hand, we recorded a small, but significant, rise of fibrinogen. Our study confirmed the importance of scheduled physical activity in the patient with intermittent claudication, showing that clinical improvement is not accompanied by an increase in the circulatory reserve. The unchanged levels of plasminogen suggest that the fibrinolytic activity does not vary significantly after a course of physical exercise.

μ- and κ-opioid receptor agonists produce peripheral inhibition of neurogenic plasma extravasation in rat skin

Extravasation elicited in rat skin by antidromic electrical stimulation of the saphenous nerve was dose dependently inhibited by the intravenous (i.v.) application of the μ-opioid receptor agonists, morphine and [D-Ala 2,Me-Phe 4,Gly-ol 5]enkephalin (DAGO), and the κ-opioid receptor agonists (−)-U 50488H, (−)-ICI 197067 and ICI 204448. This inhibition was antagonised by naloxone, and the lack of action of (+)-U 50488H (5 mg/kg) indicated that the κ effect was stereoselective. The δ-opioid receptor agonist, [D-Pen 2, D-Pen 5]enkephalin (DPDPE), and the σ-receptor agonist, (+)-SKF 10047, had no effect on neurogenic extravasation at a dose of 5 mg/kg. Opiate-induced changes in cutaneous blood flow were not important for opiate inhibition since extravasation produced by exogenous substance P (the putative neurotransmitter) was not influenced by the opiates. An indirect opiate action via the adrenal glands was excluded since the effectiveness of DAGO, (−) - ICI 197067 and ICI 204448 was unchanged after adrenalectomy. Finally, the cutaneous locus of the opiate effect was shown by blocking the activity of systematically applied DAGO and ICI 204448 with naloxone injected into paw. These results indicate that specific μ-opioid and κ-opioid, but not δ-opioid and σ receptor agonists, inhibit neurogenic plasma extravasation in rat skin, probably via opioid receptors on peripheral terminals of sensory C-fibres.

Streptozocin-Diabetes Modifies Acetylcholine Release from Mouse Phrenic Nerve Terminal and Presynaptic Sensitivity to Succinylcholine

This study was conducted to quantify the intensity of ultraviolet (UV) erythema in guinea pigs, a method for evaluating anti-inflammatory drugs, and to clarify any correlation of erythema with cutaneous blood flow. Skin color and cutaneous blood flow in non-administered and indomethacin-administered animals were measured by a colorimeter and a laser Doppler flowmeter over time after UV-irradiation treatment. Skin color was indicated by a XYZ colorimetric system and L*a*b* color space. In either colorimetric system, the values of two indices, x and y or a* and b*, increased along with the intensification of erythema. The increase in the chroma (C*) value calculated from a* and b* was UV-dose-dependent. This value was significantly suppressed by indomethacin 0.5-4 hr after irradiation, and it was found to be a clear and sensitive index for evaluating the suppressive effect of drugs. Cutaneous blood flow also increased with UV irradiation. Indomethacin significantly suppressed this increase 2-3 hr after UV irradiation. The changes of cutaneous blood flow correlated with those of C*. These results suggested C* was a suitable parameter to quantify UV erythema, and the change of skin color in UV erythema reflected the change of cutaneous blood flow.

Effect of Morphine on Changes in Cutaneous Blood Flow Induced by Antidromic Stimulation of Primary Afferent Fibers in the Hind Instep of Rats

The effects of morphine on the release of immunoreactive substance P (iSP) into the subcutaneous perfusate and the changes in cutaneous blood flow (CBF) elicited by antidromic stimulation of sectioned sciatic nerve were investigated in the instep of the hind paw of rats. Antidromic stimulation of the sectioned sciatic nerve induced a marked increase in iSP release into the subcutaneous perfusate and a biphasic flow response consisting of an initial transient decrease followed by an increase. Both the iSP release and the increase of the CBF evoked by antidromic stimulation (the second phase) were significantly inhibited by intra-arterial (i.a.) infusion of morphine (30 mumol/kg). These inhibitory effects of morphine were antagonized by pretreatment with naloxone (2 mg/kg, i.p.). The i.a. infusion of SP (0.25 mumol/kg) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. Neither phase induced by i.a. infusion of SP was affected by preinfusion of morphine (10 or 30 mumol/kg, i.a.). We suggest that morphine applied locally mainly acts on the peripheral endings of small-diameter afferent fibers, not on blood vessels, and that activation of this site is involved in the regulation of the microcirculatory hemodynamics of cutaneous tissue through inhibition of SP release.

Altered microvascular reactivity to endothelin-1, endothelin-3 and NG-nitro-L-arginine methyl ester in streptozotocin-induced diabetes mellitus.

1 We have determined the dermal microvascular effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 nmol/site), endothelin-1 (ET-1, 0.1-10 pmol/site) and ET-3 (0.1-30 pmol/site) in rats with streptozotocin (STZ)-induced diabetes mellitus. Cutaneous blood flow changes as measured by a 133xenon (133Xe) clearance technique, were determined in diabetic rats four weeks after treatment with streptozotocin (STZ) and compared with responses measured in normal rats four weeks after treatment with saline. 2 Resting skin blood flow was similar in diabetic and in normal rats, as measured by 133Xe clearance and laser Doppler flowmetry. 3 Intradermal NG-nitro-L-arginine methyl ester (L-NAME) reduced skin blood flow in normal rats by 55.2 +/- 2.6% as measured by 133Xe clearance, (n = 9). L-NAME was significantly less effective in diabetic rats, inducing a 40.9 +/- 7.7% decrease in blood flow (n = 9, P less than 0.05). The enantiomer D-NAME had no effect in either group of rats. 4 Low doses of ET-1 and ET-3 injected intradermally induced dose-dependent decreases in blood flow, measured by 133Xe clearance, which were similar in both groups of rats. However, the responses to the highest doses of ET-1 (10 pmol/site) and ET-3 (10 and 30 pmol/site) were significantly reduced in the diabetic compared with the normal rats (P less than 0.05).In addition vasoconstriction to the highest doses of vasopressin (0.3 and 3 pmol/site) and vasodilatation to the neuropeptide calcitonin gene-related peptide (CGRP, 1O pmol/site) were similarly reduced in the diabetic rats (P <0.05).5. The decrease in blood flow induced by submaximal doses of ET-1 was enhanced by co-injection with L-NAME (100 nmol/site) in both diabetic and normal rats. However, this enhanced response was significantly reduced in the diabetic rats (P<0.05). A similar pattern of responses were observed to ET-3 in the presence and absence of L-NAME.6. These results indicate that the cutaneous microvasculature of rats with STZ-induced diabetes responds differently to intradermal ET-1 and ET-3 compared with normal rats; a similarly altered vascular reactivity was observed with vasopressin and CGRP. Hence, the diabetic microcirculation has impaired responses to several vasoconstrictors and a vasodilator. The effect of the nitric oxide synthase inhibitor L-NAME is also suppressed in the diabetics, suggesting that there may be decreased local production of, or response, to nitric oxide.

Influence of morphine on the changes in cutaneous blood flow induced by antidromic stimulation of the sciatic nerve in the hind instep of rats

Influence of morphine on the changes in cutaneous blood flow induced by antidromic stimulation of the sciatic nerve in the hind instep of rats

Plasticity of sympathetic reflex organization following cross-union of inappropriate nerves in the adult cat.

1. The present study has investigated the reflex organization of sympathetic neurones and its control of autonomic effector organs following nerve injury and repair. A well-defined population of vasoconstrictor neurones supplying blood vessels of the hairy skin was forced to innervate a territory that contained some appropriate, but mainly inappropriate autonomic effector organs. For this purpose the central stump of the cut sural nerve was sutured to the peripheral stump of the cut tibial nerve 11-12 months prior to the terminal experiment. 2. The activity of postganglionic sympathetic neurones was recorded from fine strands of the sural nerve proximal to the nerve lesion. Using a laser-Doppler device cutaneous blood flow was measured in the hairless skin of the hindpaw that was now reinnervated by the sural nerve. The results show a qualitative change of the reflex organization of sympathetic neurones following cross-union of these nerves. 3. Stimulation of arterial chemoreceptors by ventilating the animals with a hypoxic gas mixture (8% O2 in N2 for 3-8 min) increased the activity in twelve out of thirteen strands containing postganglionic sympathetic fibres. The increase of sympathetic activity contrasts with results from normal animals where systemic hypoxia causes a reflex decrease of activity in postganglionic fibres of the sural nerve. 4. Reflex changes of sympathetic activity were closely followed by corresponding changes of cutaneous blood flow. Systemic hypoxia produced vasoconstriction in operated animals in contrast to the vasodilatation observed in normal animals. 5. We conclude that the reflex organization of sympathetic neurones can change qualitatively following nerve lesion when sympathetic neurones regenerate and supply inappropriate target tissues. This long-lasting change reflects the plasticity of the autonomic nervous system and can produce a sustained abnormal control of reinnervated autonomic effector organs.

Intradermal injections of bradykinin or histamine cause a flare-like vasodilatation in monkey. Evidence from laser doppler studies

The spreading cutaneous vasodilatation (flare) that follows a cutaneous injury is readily visible in humans but cannot be visualized in monkey. To determine if monkeys exhibit this neurally mediated reaction, cutaneous blood flow changes after intradermal injections of bradykinin and of histamine were monitored in the hairy skin of pentobarbital anesthetized monkeys. Using a laser Doppler device, recordings of cutaneous blood flow were made at distances of 15 and 25 mm from the injection of 50 microliters of saline, bradykinin (10(-3) M) and histamine (10(-3) M). These sites were beyond the radius of the wheal caused by bradykinin (6.3 mm) or histamine (6.8 mm). At both recording sites, both drugs caused an increase in blood flow that was significantly larger than that caused by the injection of the same volume of saline. These results provide evidence that although a flare is not visible in monkey skin, a flare-like vasodilatation does occur over an area of at least 50 mm diameter.

Significance of reactive oxygen species in distal flap necrosis and its salvage with liposomal SOD

In an attempt to elucidate whether reactive oxygen species (ROS) have a role in causing distal necrosis of random pattern flaps, and to develop measures to prevent necrosis, three experiments were made using a rat flap model. The flap-salvaging effect of liposomal supperoxide dismutase (L-SOD) was assessed. The results were as follows: (1) Measurements of changes in cutaneous blood flow in a flap, with time, revealed an initial remarkable decrease followed by gradual but significant increase in the distal portion 24 hours after operation. (2) The SOD activity in the flap continued to decrease gradually with time until 24 hours after operation both in L-SOD treated and control groups. However, SOD activity in L-SOD treated flaps was always significantly higher than in the control. (3) S-D value (survival length minus dye distance) was significantly greater in the L-SOD treated flap than in the control flap, indicating a significant effect of L-SOD in preventing the expected flap necrosis. These results suggest a possible role, in causing flap necrosis, of ROS which are generated by reperfusion following ischaemia, and the effectiveness of L-SOD in salvaging distal flap necrosis.

Use of laser Doppler flowmetry and transcutaneous oxygen tension electrodes to assess local autonomic dysfunction in patients with frozen shoulder.

The laser Doppler flowmeter (LDF), which measures changes in cutaneous blood flow, and the transcutaneous oxygen electrode which measures cutaneous perfusion, were used to study reflex changes in the microcirculation of the shoulder in 38 patients with frozen shoulder and 10 normal controls. In all controls and 22 patients with frozen shoulder, a normal LDF response to inspiration/expiration was observed. In 16 patients with frozen shoulder, LDF responses were either unilaterally or bilaterally absent. Comparison between the two patient groups showed a significant association (chi 2 = 6.43, P less than 0.02) between abnormality of response and the persistence of pain. TcPO2 was in the normal range in all patients and controls. These findings suggest that the LDF together with the TcPO2 may be a useful method of studying the skin microcirculation over the shoulder.

Relationship between phasic changes in human skin blood flow and autonomic tone

Heart rate beat-to-beat oscillations synchronous with respiration and blood pressure waves, have been found to be a marker of sympathovagal interaction in man and animals. Oscillations of heart rate, respiration, and cutaneous blood flow were simultaneously recorded to assess the relationship between autonomic nervous control and cutaneous circulation in a group of 21 healthy subjects and in a group of 6 healthy patients after brachial plexus anesthesia and consequent sympathetic blockade. In the first group, changes in posture were employed to modify autonomic tone. Relative changes in cutaneous blood flow were recorded by laser-Doppler flowmetry. Spectral analysis techniques (cross-correlation) were used to quantify the relationship between oscillations common to the recorded signals. A standing maneuver induced a significant decrease of the cross-correlation between respiratory and heart rate fluctuations (from 4.93 ± 0.16 to 4.44 ± 0.16 a.u.; P < 0.001), and a significant increase of the cross-correlation between heart rate and skin blood flow fluctuations (from 0.64 ± 0.31 to 1.33 ± 0.21 a.u.; P < 0.001), but did not modify the cross-correlation between respiratory and skin blood flow fluctuations (from 2.87 ± 0.15 to 3.04 ± 0.14 a.u.; NS). After the standing maneuver the maximum correlation between heart rate and skin blood flow was always due to oscillations in the range of 0.1 Hz (or 10-sec period), similar to the oscillations described in large arteries. Sympathetic blockade reduced significantly the cross-correlation between heart rate and skin blood flow ( P < 0.001). These results suggest that the cross-correlation between skin blood flow and heart rate at 10-sec period fluctuations can be used as an index of the influence of the autonomic tone on skin blood circulation.

Effect of captopril on skin blood flow following intradermal bradykinin measured by laser Doppler flowmetry

The effect of captopril on skin response to intradermal injection of bradykinin was investigated by laser Doppler flowmetry (LDF) and weal and flare measurements in this randomised, double-blind, placebo-controlled, cross-over balanced study. Intradermal injections of 1 and 2.5 micrograms of bradykinin and normal saline were made into the forearm skin of six healthy volunteers between 1 and 2 h (t1) and between 3 and 4 h (t2) after either 25 mg captopril or placebo. Skin blood flow outside the induced weal was monitored continuously by LDF for 15 min and the mean LDF values over the last 15 s were used for analysis. Weal and flare sizes were measured at 15 min. On the placebo days, the mean LDF output, weal volume and flare area increased with incremental bradykinin dose. Pre-treatment with captopril significantly increased LDF output following intradermal bradykinin at t1 but not at t2. At both t1 and t2, captopril significantly increased weal volume. There was no significant difference between treatments in flare areas. Skin response following intradermal normal saline, measured by the above parameters, was not affected by captopril. This study showed that captopril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation. The non-invasive technique of LDF can be used to detect the skin blood flow changes induced by intradermal bradykinin and the potentiation of this effect by captopril. It appears to be a useful and more objective method of quantifying local cutaneous blood flow changes than measurement of flare area.

Cutaneous blood flow changes during MR imaging

Cutaneous blood flow changes during MR imaging

Laser Doppler monitoring of microcirculatory changes in acute burn wounds.

Because burns are dynamic wounds that can change in apparent depth during the first 72 hours, we asked whether measuring changes in cutaneous blood flow might help predict the ultimate fate of burns that were not obviously shallow or deep. A laser Doppler flowmeter was used to study cutaneous perfusion for at least 72 hours in partial-thickness wounds on patients with burns of less than 15% TBSA and in experimental wounds of similar size on rats. Clinical wounds that healed without grafting consistently showed elevated perfusion levels which increased further within 72 hours, whereas wounds eventually requiring grafting experienced lower perfusion levels with no obvious pattern of increase. Differences between average flow levels for healing and nonhealing burns were statistically significant throughout the study period. Perfusion levels in experimental wounds were stratified according to burn severity, with shallower wounds showing a pattern of increase similar to the clinical wounds.

Cognitive Activity and Cutaneous Blood Flow

Serial subtraction and multiplication problems were performed orally by 21 healthy human subjects during two three-minute periods separated by a 22-minute rest interval. During the period of mental activity, cutaneous blood flow in the finger fell to 59%, digital cutaneous pulse pressure fell to 62%, and heart rate increased by 24% of the subjects' initial baseline values. Cutaneous blood flow in the malar region did not change. Because vasomotor control of the finger skin is principally vasoconstrictor and that of the malar area vasodilator, these results suggest that mental activity unrelated to obvious stress may provoke changes in cutaneous blood flow in areas controlled by sympathetic vasoconstrictor fibers. Simultaneous changes in digital cutaneous blood flow, digital cutaneous pulse pressure, and heart rate indicate an autonomic-mediated effect.

Cutaneous blood flow and local sweating after systemic atropine administration.

Localized cutaneous vasodilation (flush) is seen following systemic atropine administration. To verify calculated enhanced dry heat loss with actual changes in cutaneous blood flow, four men were studied in both control and atropine (0.025 mg.kg-1; im) experiments (Ta = 30 degrees C, Tdp = 7 degrees C) during moderate exercise (55% VO2 peak). Esophageal temperature (Tes) and arm sweating (ms) by local dewpoint were measured continously. Skin (forearm) blood flow (FBF) was measured twice each minute by venous occlusion plethysmography. Injection of atropine (2 mg) caused an increased sensitivity (+85%, p less than 0.01) in FBF to Tes with no change in the vasodilator threshold. An elevated Tes onset (0.3 degrees C, p less than 0.05) for sweating occurred with no change in the sensitivity of ms to Tes (-27%, p less than 0.20). No elevation in either forearm or Tsk occurred before the onset of vasodilation, however, both mean skin (Tsk) and local arm temperatures were higher in the atropine experiments after 15 min of exercise. Systemic atropine resulted in higher cutaneous vasodilation at the same core temperature with the local skin temperature following passively. The effect of systemic atropine in stimulation of increased cutaneous vasodilation is suggested to result by a combination of central and local responses which may be mediated through the release of vasoactive sustances.

The Effect of Prostaglandin D2 on the Response of Human Skin to Histamine

The interaction of prostaglandin D2 (PGD2) and histamine in human skin was studied by intradermal injection of the compounds alone or in combination in healthy volunteers. Responses were recorded by measurement of areas of wheal and erythema, and changes in cutaneous blood flow quantified using a laser Doppler flow meter. The effect of a near-threshold dose of PGD2 on histamine dose-response relationships and on the response to a single low dose of histamine were examined. Histamine caused dose-related increases in blood flow and in areas of wheal and erythema in human skin. Prostaglandin D2 caused dose-related increases in blood flow and erythema area, but not wheal area, in the dose range used. When the compounds were injected together, PGD2 did not potentiate the increase in blood flow and areas of wheal and erythema due to histamine. The modest augmentation of histamine response in the presence of PGD2 could be attributed to summation alone. The role of PGD2 in cutaneous disorders such as the physical urticarias, in which its release has been demonstrated, is therefore uncertain. In the amounts measured in the urticarias, it is unlikely alone to cause a significant cutaneous response; nor does it appear to act by potentiation of the response to histamine.

Meat tenderizer in the acute treatment of imported fire ant stings

Meat tenderizer containing the proteolytic enzyme papain was tested for therapeutic efficacy in the sting of the imported fire ant. The parameters of pain and itching were used to evaluate qualitatively the sting response in 22 healthy medical students, and the laser Doppler velocimeter was used to assess quantitatively the change in cutaneous blood flow. The results indicated that, during the acute-phase reaction, no clinically or statistically significant difference was found between stings treated with meat tenderizer and stings treated without tenderizer. Therefore we conclude that meat tenderizer is of no therapeutic value in the acute treatment of the imported fire ant sting.

Laser Doppler velocimetry to quantify UV-B induced increase in human skin blood flow.

Abstract— A laser Doppler velocimeter was used to quantify changes in cutaneous blood flow, in human subjects, after exposure to UV‐B radiation. Studies with three subjects showed a peak increase in flow at 6 h post‐irradiation. Dose‐response studies, on 8 subjects, at 24 h post‐irradiation showed that blood flow increased linearly with log UV‐B dose over a range of about 0.5 to 5 MED. Comparative studies with pigmented and non‐pigmented skins gave a quantitative measure of the photoprotective effect of melanin. The main advantage of the laser Doppler technique is that it allows easy quantification of a vascular response. However, there was no advantage when compared with detection of a visually determined threshold response, viz. a barely perceptible erythema.