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Blood flow response to noradrenaline (NA) and phenylephrine (PE) delivered by iontophoresis in unheated skin, as measured by laser-Doppler flowmetry (n = 4). Slopes were similar for NA and PE and were significantly different from zero (both p < 0.001). The final decrease in perfusion at the end of the iontophoresis period was 16.8 (20.5)% and 14.1 (8.8)% for NA and PE, respectively. Data are presented as mean ± SEM.
Source publication
Please cite this paper as: Henricson, Tesselaar, Baiat, Nilsson and Sjöberg (2011). Local Heating as a Predilatation Method for Measurement of Vasoconstrictor Responses with Laser-Doppler Flowmetry. Microcirculation 18(3), 214–220.
Studying microvascular responses to iontophoresis of vasoconstricting drugs contributes to a better understanding of t...
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Citations
... This could be because they have used a higher temperature (44, 45) ˚C to induce local vasodilation while we avoid using such high temperature to avoid complication. In a similar study (Henricson et al., 2011) preheated forearm tissue to 44 ˚C to induced vasodilation before iontophorised phenylephrine. Their results showed that phenylephrine reduced blood perfusion by 25-33%. ...
... In this procedure, no washing out step for the remaining phenylephrine in the chamber was performed. Some study suggested that drug removing can affect tissue response to the iontophorised drug (Henricson et al., 2011). Washing the drug can result in a movement that could interfere with the reading of the LDF device. ...
Phenylephrine, L-erythromethoxamine and metaraminol are selective α1-adrenoceptor agonists having phenethylamine chemical structure and used to treat a variety of clinical conditions, including sepsis, anaesthesia associated hypotension, nasal congestion, haemorrhoids, and the evaluation of eye function. Their action involves activation of α1-adrenoceptor on the smooth muscle of major organs to induce a contraction and the resultant therapeutic benefit is dependent on the maintenance of stable response. The signalling mechanism most closely linked to α1-adrenoceptors in smooth muscle is stimulation of phosphatidylinositol metabolism, which induces subsequent elevation of intracellular calcium ions. Lithium ions are also used clinically in the treatment of bipolar disorders and are known to prevent degradation of a key mediator of phosphoinositide metabolism and there are a few reports suggest that this cation can enhance or maintain contractions mediated by α1-adrenoceptors. In the present study, I have investigated the interaction between lithium ions and constrictor responses to a variety of agonists, including selective α1-adrenoceptor agonists, with a particular focus on both the potency of the constrictor agent and the time course of responses. I have also used pharmacological approaches to better understand the basis of a novel interaction between lithium ions and selective α1-adrenoceptor agonists. Two methods have been employed. Isometric tension recording of isolated vascular and urethral smooth muscle determined using a standard approach of maintaining the tissue in Krebs-Henseliet solution gassed with 95%O2/5%CO2. Agonists were added either cumulatively or as a single concentration and the magnitude and time course of the contraction assessed with lithium and in the presence of selective inhibitors. In addition, the time of course of changes in human skin blood flow, using laser Doppler flowmetry, to the iontophoretic application of phenylephrine has also been evaluated. Our in vitro results show that the contractions of the isolated vascular smooth muscle to KCl and the thromboxane mimetic (U46619), were sustained for up to three hours. In contrast contraction to high concentrations to noradrenaline, 5HT, histamine, vasopressin, angiotensin II, carbachol and the selective α1-adrenoceptor agonist were not. Furthermore, in porcine isolated splenic artery segments, the use of therapeutic concentration of lithium (1mM) increased the maximum response to the selective α1-adrenoceptor agonists (and carbachol) almost 2 fold it did not increase the sensitivity of the tissue to these drugs. In contrast, the time course of responses to noradrenaline, cirazoline, 5HT, histamine, vasopressin and angiotensin II was not affected by lithium. Interestingly, similar interaction was also reported in isolated porcine renal and mesenteric arteries, splenic vein and urethral smooth muscle. Moreover, our results showed that this interaction is sensitive to Ca2+ and abolished in the absence of this cation. This interaction prevents the desensitisation of the receptors which develop following the repetitive exposure to a high concentration of α1-adrenoceptor agonists. Furthermore, we confirm that this synergistic interaction is not related to internalisation, or inhibition of inositol monophosphatase, glycogen synthase kinase, Rho kinase or nitric oxide pathways. Although we reported similar enhancement in the time course of phenylephrine using nM of Na+-K+ ATPase inhibitor (ouabain), the magnitude of the response was much smaller than that reported with lithium. Our in vivo results demonstrate that the time course of contraction induced by iontophoresis of phenylephrine was relatively stable for more than 30 minutes which suggest that the concentrations reaching the superficial blood vessels were low and therefore there was no point of investigating the effect of lithium on the contraction induced by phenylephrine in this system. In conclusion, I have demonstrated that the use of high concentration of phenethylamine derived α1-adrenoceptor agonists synergistically interact with therapeutics concentration of LiCl in various smooth muscle preparations and that phosphoinositide metabolism is not involved. This synergistic effect appeared as sustain in the time course of the contraction induced by these agonists and could be accompanied by an enhancement in the magnitudes of the response. Further clinical studies using different approaches are needed to detect any potential clinical uses of this interaction.
... Transdermal iontophoresis can be used to stimulate pharmacological provocations in the skin, by delivering agonists or antagonists that specifically target receptors or pathways involved in microvascular regulation [1]. The technique has been used to deliver various agonists, including acetylcholine and sodium nitroprusside [2], insulin [3][4][5], noradrenaline and phenylephrine [6]. It has also been used to deliver receptor antagonists such as endothelin receptor antagonists [7], atropine [8], adrenoceptor antagonists [9] and the NOS pathway inhibitor L-NAME [3]. ...
... This method is also commonly used to normalize responses in traditional in vitro models [11]. Another method to predilate the microvascular bed in the skin is by local heating [6]. ...
Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques.Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi.Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p
Background
Food allergy is the commonest cause of anaphylaxis. Changes in posture during acute reactions can trigger fatal outcomes, but the impact of allergic reactions on the cardiovascular system in non-fatal reactions remains poorly understood.
Objective
To systematically evaluate changes in cardiovascular function during acute allergic reactions to peanut.
Methods
Participants underwent double-blind placebo-controlled food challenge to peanut as part of a clinical trial. Changes in hemodynamic parameters (heart rate, stroke volume, blood pressure, peripheral blood flow) and electrocardiogram during food challenges were assessed using continuous monitoring. ClinicalTrials.gov Identifier: NCT02665793
Results
57 adults (median age 24 (IQR 20-29) years, 53% female) participated; 22 (39%) had anaphylaxis. Acute reactions were associated with significant changes in stroke volume (mean decrease 4.2%, 95%CI 0.8 to 7.6; p=0.03), heart rate (mean increase 11.6%, 95%CI 8.4 to 14.8; p<0.0001) and peripheral blood flow (mean increase 19.7%, 95%CI 10.8 to 28.6; p<0.0001), irrespective of reaction severity. These changes were reproduced at subsequent repeat peanut challenge in 26 participants, and could be reversed with administration of intravenous fluids which resulted in faster resolution of abdominal symptoms.
Conclusions
In this first detailed human study of cardiovascular changes during food-allergic reactions, we found evidence for significant fluid redistribution, independent of reaction severity. This provides a sound rationale for optimizing venous return during significant allergic reactions to food. Finally, these data provide a new paradigm for understanding severity in anaphylaxis, where poor outcomes occur due to a failure in compensatory mechanisms.
