| 1. |
- Droog Tesselaar, Erik, et al.
(författare)
-
Nonspecific vasodilatation during transdermal iontophoresis : the effect of voltage over the skin
- 2003
-
Ingår i: Microvascular research. - 0026-2862. ; 65:3, s. 172-178
-
Tidskriftsartikel (refereegranskat)abstract
- We used laser Doppler perfusion imaging (LDPI) to study nonspecific vasodilatation during iontophoresis. In iontophoresis studies, nonspecific vasodilatation occurs as a result either of galvanic currents or of the applied voltage over the skin. We made dose–response measurements to study the effect of ionic strength of the vehicle on the nonspecific vasodilatation during iontophoresis of sodium chloride and deionized water, while we monitored the voltage over the skin. We found that anodal and cathodal ionotophoresis induced a voltage over the skin that was dependent on the ionic strength of the test solution. The nonspecific vasodilatation during anodal iontophoresis was less pronounced than during cathodal iontophoresis, and was independent of the voltage over the skin. The nonspecific vasodilatation in cathodal iontophoresis was related to the voltage over the skin, and was possibly mediated by depolarization of local sensory nerves. In experiments using cathodal iontophoresis, therefore, the ionic strengths of the vehicle and the drug are important when vasoactive drugs are examined, as the nonspecific vasodilatation needs to be controlled for. As the vasodilatation that we observed was heterogeneously distributed within the area of iontophoresis, LDPI may provide more accurate measurements than conventional laser Doppler perfusion monitoring.
|
|
| 2. |
- Arildsson, Mikael, 1967-, et al.
(författare)
-
Effects on skin blood flow by provocation during local analgesia
- 2000
-
Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 59:1, s. 122-130
-
Tidskriftsartikel (refereegranskat)abstract
- Although topical analgesia cream has been used for several years, little is known about its effects on the microcirculation. Previous studies have shown a vasoconstrictive effect after short application times and a vasodilatation after longer application. It has also been shown that vasomotion does not occur in the analgesized skin. The present study was undertaken to investigate the alterations in skin blood perfusion following local cooling, local heating and pin-pricking after the establishment of analgesia. In 11 healthy volunteers, skin analgesia was attained by use of a eutectic mixture of lidocaine and prilocaine (EMLA, Astra Pain Control AB, Sweden) applied to the skin three hours prior to provocation. The changes in skin blood perfusion, after applying three different provocation methods, were studied using the laser Doppler technique. Local cooling and heating to temperatures of +10 and +45°C, respectively, were applied for 9 s by use of a copper probe (Ø12 mm). In the pin-prick provocation method, a combined effect of deflection and penetration of the skin to in total 3 mm was attained. Identical provocation methods were applied to placebo treated and untreated skin areas. After heat provocation, significant differences in the perfusion response between the treatments were seen (P < 0.0001). Skin areas treated with analgesia cream responded with a slow increase in perfusion that persisted beyond the four minute measurement period. Placebo and untreated areas decreased their perfusion over time. After cooling a significant reduction in skin perfusion was seen, irrespective of the treatment. Similarly, after pin-pricking a perfusion increase was seen for all treatments. The findings indicate that topical analgesia influences the myogenic control of the blood flow in those vascular plexa measured by laser Doppler following heat provocation. No differences could be seen in the response to pin-pricking and cooling for the different treatments.
|
|
| 3. |
- Arildsson, Mikael, 1967-, et al.
(författare)
-
Skin capillary appearance and skin microvascular perfusion due to topical application of analgesia cream
- 2000
-
Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 59:1, s. 14-23
-
Tidskriftsartikel (refereegranskat)abstract
- Local topical analgesia changes basal skin perfusion and its regulation. In particular, the response induced by local heating, which in nontreated skin comprises a rapidly increased perfusion followed by a normalization within 30 s, is altered to a delayed and persistent perfusion increase. The response dependency to the analgesia cream application time, that is, the intradermal penetration of the analgesics and in which vascular plexa the response occurs, is not known. The aim of this study was to assess changes in the appearance of superficial skin capillaries and skin microvascular perfusion changes due to different application periods of topical analgesia cream (EMLA). Twelve subjects were treated with EMLA and placebo applied to the volar side of each forearm, respectively. The treatment areas were assigned different application times (20 min, 40 min, 1 h, 2 h, and 3 h). The areas were cleared from the creams and shortly thereafter provoked during 9 s with a probe heated to 45°C. To assess capillary number density and skin perfusion, capillary microscopy, and Laser Doppler perfusion imaging (LDPI), respectively, were used. The number density of physiologically active capillary was significantly decreased with longer application times of EMLA (P < 0.005). The LDPI-signal showed a persistent perfusion increase after provocation associated with increasing application time of the cream. This perfusion pattern was not seen after 20 min of treatment, but was present in 9 of 12 subjects after 3 h of treatment. No significant relationship between changes in the capillary number density and the LDF measurement was found. In conclusion, a longer application time and therefore a higher intradermal concentration and a deeper penetration of the analgesics was associated with a delayed and persistent perfusion increase after local heating. There was a discrepancy between changes in capillary number density and skin perfusion, indicating that the perfusion increase does not occur in the capillaries but in the deeper lying vessels. Hence, the contribution of the capillary perfusion to the LDF-signal is smaller than previously anticipated. Capillary number density and presumably their perfusion were decreased with longer application times.
|
|
| 4. |
- Bentzer, Peter, et al.
(författare)
-
Endothelin-1 Reduces Microvascular Fluid Permeability through Secondary Release of Prostacyclin in Cat Skeletal Muscle.
- 2002
-
Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 63:1, s. 50-60
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to analyze effects of various plasma concentrations of the vasoconstrictor endothelin-1 on microvascular fluid permeability and on transcapillary fluid exchange. We also analyzed whether the permeability-reducing substance prostacyclin is involved in the permeability effects of endothelin-1, as prostacylin is suggested to be released via ET(B) receptor stimulation. The study was performed on an autoperfused cat calf muscle preparation, and a capillary filtration coefficient (CFC) technique was used to estimate variations in microvascular fluid permeability (conductivity). Intraarterial infusion of endothelin-1 in low doses (5 and 10 ng/min/100 g muscle) caused transcapillary absorption, whereas higher doses (20-40 ng/min/100 g) induced filtration despite further vasoconstriction. Low-dose endothelin-1 had no significant effect on CFC, while CFC was reduced to at most 55% of baseline at higher doses (P < 0.01). Simultaneous local intraarterial infusion of the prostacyclin synthesis inhibitor tranylcypromine restored CFC to 114% of baseline (P < 0.01) and further increased vascular resistance. A low, nonvasodilator dose of prostacyclin given intravenously counteracted the tranylcypromine effect on CFC. The decreased CFC induced by a high dose of endothelin-1 was counteracted by the ET(B) receptor antagonist BQ-788 with no change in vascular resistance (P < 0.05). We conclude that the decreased CFC following high doses of endothelin-1 can be attributed to a decrease in microvascular hydraulic conductivity, mediated by secondary release of prostacylin via stimulation of the ET(B) receptor. Endothelin-1 may induce edema through postcapillary vasoconstriction. (c)2001 Elsevier Science.
|
|
| 5. |
- Droog Tesselaar, Erik, et al.
(författare)
-
A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects
- 2004
-
Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 197-202
-
Tidskriftsartikel (refereegranskat)abstract
- Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm2), charge density (mC/cm2), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP). We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm2) and charge density (<7.8 mC/cm2) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.
|
|
| 6. |
|
|
| 7. |
- Hjalmarsson, Clara, 1969, et al.
(författare)
-
Electron microscopic evaluation of the endothelial surface layer of glomerular capillaries.
- 2004
-
Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:1, s. 9-17
-
Tidskriftsartikel (refereegranskat)abstract
- Recent data from various vascular beds suggest that a layer of mucopolysaccharides covering the endothelial cells play an important role in transport processes, among others. In this study, electron microscopy (EM) was used to explore the presence of an endothelial surface layer (ESL) in rat glomerular capillaries. We adopted various fixation and labeling techniques, as follows: (1) negatively charged lipid particles were used as a tracer that was expected to be excluded from the ESL. The density of intravascular lipid particles in flow-arrested capillaries was 89% lower in a 200-nm periendothelial area than in the rest of the luminal space (n = 6 rats, P < 0.001); (2) podocytes of cryofixed fresh tissue had a 20-nm extramembranous coat, interpreted as the true glycocalyx; the coat was less expressed on the endothelium; (3) on unfixed endothelial cells, colloidal lanthanum labeled a 60-nm-thick layer, occasionally forming lumps; (4) perfusion with a fluorocarbon-based oxygen-carrying fixative, followed by tannic acid contrast enhancement, revealed an extensive (> 200 nm) ESL not previously described; however, this finding was restricted to superficial glomerular capillaries; (5) Cupromeronic Blue cytochemistry displayed a loose proteoglycan network in fenestral openings and, occasionally, a semiordered ESL; (6) ferricyanide-reduced osmication resulted in increased numbers of fenestral diaphragms. In conclusion, this study provides novel morphological evidence to support the presence of a significant glomerular ESL.
|
|
| 8. |
- Horiuchi, Yoshihito, et al.
(författare)
-
Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis
- 2004
-
Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 192-196
-
Tidskriftsartikel (refereegranskat)abstract
- Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60–65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.
|
|
| 9. |
- Häggblad, Erik, 1972-, et al.
(författare)
-
Reflection Spectroscopy of Analgesized Skin
- 2001
-
Ingår i: Microvascular Research. - : ScienceDirect. - 0026-2862 .- 1095-9319. ; 62:3, s. 392-400
-
Tidskriftsartikel (refereegranskat)abstract
- Analgesized skin, when subjected to heat stimuli, responds by increasing skin perfusion. This response does not originate from increased perfusion in superficial capillaries, but rather in the deeper lying vessels. The aim of this study was to assess changes in blood chromophore content, measured by reflection spectroscopy, in relation to the perfusion increase, especially regarding the chromophores oxyhemoglobin and deoxyhemoglobin. Eleven normal subjects were treated with analgesic cream (EMLA) and placebo for 20, 40, 60, 120, and 180 min. Individual reactions to local heating were classified as responses if the change in reflection data or the change in perfusion, as measured by laser Doppler blood flowmetry, exceeded 2 standard deviations of normal variation. The increase in blood perfusion or in blood content gave rise to an increased absorption, interpreted as an increase due mainly to the chromophore oxyhemoglobin. The number of responses increased with increased treatment time for EMLA-treated areas. In general, there was a good agreement between both methods; 44 of 55 classifications coincided for the two methods used. In conclusion, analgesized forearm skin, which had been exposed to local heating, responded with an elevated perfusion consisting of oxygenated blood. This strengthens the hypothesis that the flow increase occurs through dilatation of larger deeper lying skin vessels and not in the capillaries.
|
|
| 10. |
- Lundblad, Cornelia, et al.
(författare)
-
The permeability-reducing effects of prostacyclin and inhibition of Rho kinase do not counteract endotoxin-induced increase in permeability in cat skeletal muscle.
- 2004
-
Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 68:3, s. 286-294
-
Tidskriftsartikel (refereegranskat)abstract
- cAMP stimulation and Rho kinase inhibition are shown to decrease microvascular permeability during noninflammatory conditions, most likely by decreasing contractility of actomyosin filaments in the endothelial cell, but their effects on permeability during inflammatory conditions are not clarified. The objective of this in vivo study, performed on the autoperfused and denervated calf muscle of the cat, was therefore to evaluate to what extent cAMP stimulation and inhibition of Rho kinase reduce permeability at endotoxemia. Change in osmotic reflection coefficient for albumin was used as a measure of altered protein permeability and change in capillary filtration coefficient (CFC) as a measure of altered fluid permeability. After inducing a significant increase in protein and fluid permeability by infusion of lipopolysaccharide (LPS), we determined to what extent the increased permeability was decreased by the cAMP stimulator prostacyclin [1.0 ng/kg/min intravenously (iv)] or the Rho kinase inhibitor Y-27632 [1.05 μg/ml plasma/h intraarterially (ia)]. These doses are known to decrease permeability under noninflammatory conditions. The reflection coefficient for albumin and CFC were determined before and during LPS, and during LPS plus prostacyclin (n = 6) or LPS plus Y-27632 (n = 6). The reflection coefficient was reduced by about 30% (P < 0.05) and CFC was increased by about 25% (P < 0.05) by LPS, and these permeability parameters were not affected by prostacyclin or Y-27632. We conclude that cAMP stimulation and Rho kinase inhibition reduce permeability by other pathways and mechanisms than those by which permeability is increased during endotoxemia.
|
|
| 11. |
|
|
| 12. |
|
|
