Vasoactive properties of lignocaine administered by iontophoresis in human skin

The vasoactivity of lignocaine has an important influence on its clinical efficacy and systemic vascular absorption. The aim of this study was to evaluate its vasoactive properties when administered by the non-invasive technique of iontophoresis. We used laser Doppler imaging to measure the forearm skin blood flow responses of seven healthy young males to iontophoretic delivery of two preparations of 20g/l of lignocaine hydrochloride, one containing the preservatives methylparaben and propylparaben and one without. The subjects were blind to the order of drug administration, and we assessed analgesia at the sites using a pinprick test. Delivery of both preparations of (positively charged) lignocaine under the anode caused demonstrable analgesia, but no change in skin blood flow. An increase in perfusion was measured, however, when the preservative-containing preparation was administered under the cathode. There was little or no response to the solution without preservatives, although the difference in response between the two preparations was not statistically significant (P = 0.063). Although there were no vasoactive effects of lignocaine at the relatively low dose used in the present study, our results suggest that the preservatives methylparaben and propylparaben are the most likely cause of the vasodilatation that we observed under the cathode, and may therefore have a significant influence on the vasoactivity of this preparation when administered by injection. Both are negatively charged in solution and have been reported to possess vasodilator properties. It might be worth considering the use of alternative, non-vasoactive preservatives in local anaesthetic preparations, or avoiding the use of additives altogether, when this is feasible.

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Laser Doppler Imaging of Finger Skin Blood Flow in Patients after Microvascular Repair of the Ulnar Artery at the Wrist

Journal of Hand Surgery (European Volume) ◽

10.1016/0266-7681(94)90075-2 ◽

1994 ◽

Vol 19 (3) ◽

pp. 295-300 ◽

Cited By ~ 21

Author(s):

S. BORNMYR ◽

M. ARNER ◽

H. SVENSSON

Keyword(s):

Blood Flow ◽

Skin Blood Flow ◽

Ulnar Artery ◽

Laser Doppler ◽

Doppler Imaging ◽

Invasive Technique ◽

Microvascular Reconstruction ◽

Laser Doppler Imaging ◽

Non Invasive ◽

Finger Tip

Laser Doppler imaging is a new, non-invasive technique allowing the spatial distribution and the temporal variation of the skin blood flow to be monitored. A mean blood flow value over an area, such as the finger-tip in the present study, can also be calculated. Recordings from 12 patients with a sutured ulnar artery following trauma did not significantly differ from those obtained in 14 controls. Four patients with a ligated ulnar artery, however, showed a slower restitution of blood flow values after cold provocation. All sutured ulnar arteries were found to be patent, which confirms that microvascular reconstruction of an injury to the ulnar artery at the wrist is worthwhile.

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Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00373.2004 ◽

2004 ◽

Vol 97 (3) ◽

pp. 883-887 ◽

Cited By ~ 22

Author(s):

Faisel Khan ◽

David J. Newton ◽

Emily C. Smyth ◽

Jill J. F. Belch

Keyword(s):

Blood Flow ◽

Sodium Nitroprusside ◽

Electrical Resistance ◽

Deionized Water ◽

Microvascular Function ◽

Doppler Imaging ◽

Laser Doppler Imaging ◽

Valuable Method ◽

Forearm Skin ◽

Iontophoretic Delivery

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

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Low-pressure sequential compression of lower limbs enhances forearm skin blood flow

Clinical & Investigative Medicine ◽

10.25011/cim.v39i6.27488 ◽

2016 ◽

Vol 39 (6) ◽

pp. 204 ◽

Cited By ~ 1

Author(s):

Guy Amah ◽

Sebastian Voicu ◽

Philippe Bonnin ◽

Nathalie Kubis

Keyword(s):

Blood Flow ◽

Skin Blood Flow ◽

Cardiac Cycle ◽

Low Pressure ◽

Lower Limbs ◽

Test Results ◽

Skin Microcirculation ◽

Doppler Flowmetry ◽

Non Invasive ◽

Forearm Skin

Purpose: We investigated whether forearm skin blood flow could be improved when a multilayer pulsatile inflatable suit was applied at a low pressure to the lower limbs and abdomen. We hypothesized that a non-invasive purely mechanical stimulation of the lower limbs could induce remote forearm blood flow modifications. Methods: The pulsatile suit induced a sequential compartmentalized low compression (65 mmHg), which was synchronized with each diastole of the cardiac cycle with each phase evolving centripetally (lower limbs to abdomen). Modifications of the forearm skin blood flow were continuously recorded by laser Doppler flowmetry (LDF) at baseline and during the pulsatile suit application. Endothelium-dependent and endothelium-independent vasodilations of the forearm skin microcirculation were measured by LDF in response to a local transdermal iontophoretic application of acetylcholine (ACh-test) and to hyperthermia (hyperT- test). Results: Twenty-four healthy volunteers, 12 men and 12 women (43±14 years) were included in the study. LDF responses increased 1) under pulsatile suit (97±106%, p

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Reconstruction of input functions from a dynamic PET image with sequential administration of 15O2 and H215O for noninvasive and ultra-rapid measurement of CBF, OEF, and CMRO2

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x17713574 ◽

2017 ◽

Vol 38 (5) ◽

pp. 780-792 ◽

Cited By ~ 2

Author(s):

Nobuyuki Kudomi ◽

Yukito Maeda ◽

Hiroyuki Yamamoto ◽

Yuka Yamamoto ◽

Tetsuhiro Hatakeyama ◽

...

Keyword(s):

Rate Constants ◽

Human Subjects ◽

Invasive Procedure ◽

Invasive Technique ◽

Invasive Approach ◽

Non Invasive ◽

Sequential Administration ◽

Invasive Method ◽

The Difference ◽

Arterial Input Functions

CBF, OEF, and CMRO2 images can be quantitatively assessed using PET. Their image calculation requires arterial input functions, which require invasive procedure. The aim of the present study was to develop a non-invasive approach with image-derived input functions (IDIFs) using an image from an ultra-rapid O2 and C15O2 protocol. Our technique consists of using a formula to express the input using tissue curve with rate constants. For multiple tissue curves, the rate constants were estimated so as to minimize the differences of the inputs using the multiple tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects ( n = 24). The estimated IDIFs were well-reproduced against the measured ones. The difference in the calculated CBF, OEF, and CMRO2 values by the two methods was small (<10%) against the invasive method, and the values showed tight correlations ( r = 0.97). The simulation showed errors associated with the assumed parameters were less than ∼10%. Our results demonstrate that IDIFs can be reconstructed from tissue curves, suggesting the possibility of using a non-invasive technique to assess CBF, OEF, and CMRO2.

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Transcutaneous hydrogen clearance-a new non-invasive technique for assessing blood flow in human skin

Physiological Measurement ◽

10.1088/0967-3334/15/1/008 ◽

1994 ◽

Vol 15 (1) ◽

pp. 89-100 ◽

Cited By ~ 1

Author(s):

D K Harrison ◽

R Abi Raad ◽

D Newton ◽

P T McCollum

Keyword(s):

Blood Flow ◽

Human Skin ◽

Invasive Technique ◽

Non Invasive ◽

Hydrogen Clearance

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Interactions between local and reflex influences on human forearm skin blood flow

Journal of Applied Physiology ◽

10.1152/jappl.1976.41.6.826 ◽

1976 ◽

Vol 41 (6) ◽

pp. 826-831 ◽

Cited By ~ 77

Author(s):

J. M. Johnson ◽

G. L. Brengelmann ◽

L. B. Rowell

Keyword(s):

Blood Flow ◽

Skin Blood Flow ◽

Forearm Blood Flow ◽

Lower Body Negative Pressure ◽

Muscle Blood Flow ◽

Whole Body ◽

Vasoconstrictor Response ◽

Human Forearm ◽

Forearm Skin ◽

Forearm Muscle

A three-part experiment was designed to examine interactions between local and reflex influences on forearm skin blood flow (SkBF). In part I locally increasing arm skin temperature (Tsk) to 42.5 degrees C was not associated with increases in underlying forearm muscle blood flow, esophageal temperature (Tes), or forearm blood flow in the contralateral cool arm. In part II whole-body Tsk was held at 38 or 40 degrees C and the surface temperature of one arm held at 38 or 42 degrees C for prolonged periods. SkBF in the heated arm rose rapidly with the elevation in body Tsk and arm Tsk continued to rise as Tes rose. SkBF in the arm kept at 32 degrees C paralleled rising Tes. In six studies, SkBF in the cool arm ultimately converged with SkBF in the heated arm. In eight other studies, heated arm SkBF maintained an offset above cool arm SkBF throughout the period of whole-body heating. In part III, local arm Tsk of 42.5 degrees C did not abolish skin vasoconstrictor response to lower body negative pressure. We conclude that local and reflex influences to skin interact so as to modify the degree but not the pattern of skin vasomotor response.

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Assessment of microvascular endothelial function in human skin

Clinical Science ◽

10.1042/cs1010567 ◽

2001 ◽

Vol 101 (6) ◽

pp. 567-572 ◽

Cited By ~ 34

Author(s):

David J. NEWTON ◽

Faisel KHAN ◽

Jill J.F. BELCH

Keyword(s):

Blood Flow ◽

Substance P ◽

Endothelial Function ◽

Animal Studies ◽

Doppler Imaging ◽

Microvascular Blood Flow ◽

Coefficients Of Variation ◽

Forearm Skin ◽

Invasive Techniques ◽

Dose Dependent

Endothelial dysfunction is an important factor in many cardiovascular diseases, and is commonly associated with impaired endothelium-mediated vasodilatation. Information about the mechanisms behind this dysfunction has come largely from animal studies or, in humans, through invasive techniques that are not specific to one vascular bed. We have developed protocols to assess endothelial function non-invasively in the cutaneous microcirculation by measuring blood flow responses to four receptor-specific vasoactive compounds. Cumulative doses of acetylcholine, methacholine, bradykinin and substance P were administered iontophoretically to the forearm skin of healthy volunteers on two to three occasions. Dose-dependent increases in skin microvascular blood flow in response to these drugs were measured with laser Doppler imaging. Vascular responses to acetylcholine and methacholine were reasonably consistent, with coefficients of variation of approx. 17%. The coefficients of variation for bradykinin and substance P were much poorer, as high as 70% for some doses. This might partly be a consequence of the more unpredictable effects of histamine release in the vasoactive behaviour of these two agonists. Although it might be advantageous to find other agonists with which to test the function of different receptor pathways, we have shown that just acetylcholine and methacholine can currently be used with iontophoresis to allow sensitive and reproducible assessment of endothelial function.

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