psd-502 and Hyperemia

Different topical local anaesthetics have varying effects on skin blood flow and vascular reactivity. We compared the vasoactive properties of Rapydan, a new topical local anaesthetic, with those of Ametop and EMLA creams in 20 healthy volunteers. Blood flow and vascular reactivity in the forearm skin were assessed by laser Doppler flowmetry and the transient hyperaemic response ratio respectively, before and after the application of EMLA (for 60 min), Ametop (for 30 and 60 min) and Rapydan (for 30 min). Application of EMLA had no effect on skin blood flow (median (IQR [range]) change from baseline -0.9% (-63 to 414 [-38.5 to 51.3] %, p = 1.0)) or mean (SD) transient hyperaemic response ratio (from 2.86 (0.86) to 3.17 (1.3), p = 0.38). The application of Ametop for 60 min produced a greater median (IQR [range]) increase in blood flow from baseline (508 (-55 to 998 [148-649]) %) than Rapydan applied for 30 min 160 (-77 to 997 [45-301]) %, p = 0.001), and a similar decrease in mean (SD) transient hyperaemic response ratio (from 2.69 (1.16) to 1.08 (0.26) and from 2.83 (0.84) to 1.49 (0.93) respectively, p = 0.57).

Topics: Administration, Cutaneous; Adult; Anesthesia, Local; Anesthetics, Combined; Anesthetics, Local; Bandages; Drug Delivery Systems; Forearm; Humans; Hyperemia; Laser-Doppler Flowmetry; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Prilocaine; Regional Blood Flow; Skin; Tetracaine; Young Adult

Local anaesthetics affect blood vessels in various ways, depending upon the site of action and the drug used. There is controversy over the vascular effects of two widely used topical local anaesthetic agents, EMLA and Ametop. We used the transient hyperaemic response (THR) to the brief compression of the brachial artery to assess vascular reactivity of forearm skin after application of topical local anaesthesia.. Twenty healthy male volunteers were studied. Forearm blood flow-flux was measured using laser Doppler flowmetry, and the magnitude of the hyperaemic response to brachial artery occlusion for 20 s was recorded. Control cream, EMLA, or Ametop were applied and covered with an occlusive dressing for 60 min. Blood flow-flux and the hyperaemic response measurements were then repeated, with the laser Doppler probes sited over the areas of skin to which the local anaesthetic creams had been applied. Measurements were made at 60, 90, and 120 min after the application of the creams. The THR ratio (THRR) was calculated at each time point, defined as the net hyperaemic flow-flux divided by the baseline flow-flux.. At 60 min, Ametop caused a significantly greater increase in blood flow and decrease in THRR over control than EMLA [net increase of mean blood flow (SD) over control 95 (61) vs 2 (17) AU (P<0.001), net mean THRR decrease over control 1.33 (1.85) vs -0.34 (1.33) (P<0.02)].. The application of topical Ametop decreases microvascular tone and vasoreactivity of the forearm skin in healthy volunteers.

Topics: Adult; Anesthetics, Local; Blood Flow Velocity; Forearm; Humans; Hyperemia; Laser-Doppler Flowmetry; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Microcirculation; Prilocaine; Regional Blood Flow; Skin; Tetracaine; Vasodilation

Post-occlusive and local thermal hyperemia are currently used as integrated tests to study microvascular function in microvascular diseases. However, further pathophysiological insight would require its association with microdialysis. The major limitation remains the microinvasive approach as local anaesthesia prior to fiber insertion could lead to confounding effects. The objective of our study was to determine whether EMLA cream treatment, applied for 20 min, 40 or 60 min, significantly decreases the pain related to intradermal needle insertions, while not decreasing the microvascular response to post-occlusive and thermal hyperemia 2 h after cream removal. EMLA cream, when applied during 40 min, induces a significant 75% decrease in the pain following intradermal needle insertion, while not modifying skin post-occlusive and thermal hyperemia 2 h after cream removal. Therefore, we recommend its use in such conditions before performing microdialysis coupled with laser Doppler flowmetry in cohort studies aimed at studying microvascular dysfunction in patients with microvascular diseases.

Topics: Administration, Topical; Adult; Anesthetics, Combined; Anesthetics, Local; Blood Flow Velocity; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperemia; Injections, Intradermal; Laser-Doppler Flowmetry; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Microcirculation; Microdialysis; Needles; Ointments; Pain; Pain Measurement; Pain Threshold; Prilocaine; Skin; Time Factors

To investigate cutaneous sensory nerve contribution to hyperaemia following chronic shear stress training.. Eleven males underwent a shear stress intervention (forearm occlusion 5 s, rest 10 s) for 30 min, 5 times·week. In response to local heating, EMLA treatment significantly delayed the onset of vasodilatation (p < 0.001), time-to-peak (p < 0.001), time to 39 °C (p < 0.02), time to 42 °C (p < 0.006), but not time to 44 °C (p > 0.2). EMLA treatment also increased time-to-peak for PORH (p ≤ 0.01). In the experimental limb after 6 weeks, both onset time and time to peak were shorter in response to local heating at the untreated and EMLA-treated sites (all p < 0.001). There were no changes in time-to-peak for PORH at the untreated and EMLA-treated sites (p ≥ 0.4); however, the peak PORH response was reduced with EMLA treatment (p ≤ 0.03). The 6-week intervention increased the peak PORH at the untreated sites (p < 0.001) but not at EMLA-treated (p > 0.05) sites. Comparing the control limb before and after 6 weeks, no differences in responses occurred at either the untreated skin sites (p ≥ 0.9) or the EMLA-treated sites (p ≥ 0.9).. Sensory nerve blockade attenuated the improvements in cutaneous vascular responses to thermal hyperaemia and PORH following chronic exposure to shear stress. These data demonstrate an important role for sensory nerve function in the initiation of vasodilatation to both PORH and thermal hyperaemia, in both the time to onset and the magnitude of vasodilatation.

Topics: Adult; Anesthetics, Local; Blood Flow Velocity; Blood Vessels; Body Temperature Regulation; Forearm; Humans; Hyperemia; Hyperthermia, Induced; Lidocaine, Prilocaine Drug Combination; Male; Regional Blood Flow; Sensory Receptor Cells; Skin; Stress, Mechanical; Time Factors; Vasodilation; Young Adult

Topics: Anesthetics, Local; Capsaicin; Hot Temperature; Humans; Hyperemia; Lidocaine; Lidocaine, Prilocaine Drug Combination; Nitric Oxide; Prilocaine; Regional Blood Flow; Sensory Receptor Cells; Skin; TRPV Cation Channels

Reactive hyperaemia is the increase in blood flow following arterial occlusion. The exact mechanisms mediating this response in skin are not fully understood. The purpose of this study was to investigate the individual and combined contributions of (1) sensory nerves and large-conductance calcium activated potassium (BKCa) channels, and (2) nitric oxide (NO) and prostanoids to cutaneous reactive hyperaemia. Laser-Doppler flowmetry was used to measure skin blood flow in a total of 18 subjects. Peak blood flow (BF) was defined as the highest blood flow value after release of the pressure cuff. Total hyperaemic response was calculated by taking the area under the curve (AUC) of the hyperaemic response minus baseline. Infusates were perfused through forearm skin using microdialysis in four sites. In the sensory nerve/BKCa protocol: (1) EMLA cream (EMLA, applied topically to skin surface), (2) tetraethylammonium (TEA), (3) EMLA + TEA (Combo), and (4) Ringer solution (Control). In the prostanoid/NO protocol: (1) ketorolac (Keto), (2) NG-nitro-l-arginine methyl ester (L-NAME), (3) Keto + l-NAME (Combo), and (4) Ringer solution (Control). CVC was calculated as flux/mean arterial pressure and normalized to maximal flow. Hyperaemic responses in Control (1389 +/- 794%CVC max s) were significantly greater compared to TEA, EMLA and Combo sites (TEA, 630 +/- 512, P = 0.003; EMLA, 421 +/- 216, P < 0.001; Combo, 201 +/- 200, P < 0.001%CVC max s). Furthermore, AUC in Combo (Keto + l-NAME) site was significantly greater than Control (4109 +/- 2777 versus 1295 +/- 368%CVC max s). These data suggest (1) sensory nerves and BKCa channels play major roles in the EDHF component of reactive hyperaemia and appear to work partly independent of each other, and (2) the COX pathway does not appear to have a vasodilatory role in cutaneous reactive hyperaemia.

Topics: Adult; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Female; Humans; Hyperemia; Ketorolac; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Neurons, Afferent; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidants; Potassium Channel Blockers; Prilocaine; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Regional Blood Flow; Skin; Tetraethylammonium