Abnormalities in Cutaneous Microcirculation in Patients with Alzheimer’s Disease, Mild Cognitive Impairment, and Chronic Insomnia Disorder

Impaired sympathetic response is frequently observed in neurodegenerative diseases, such as Alzheimer’s disease (AD). On the other hand, chronic insomnia disorder (CID) is also often accompanied by activation of sympathetic nerves. Considering that cutaneous microcirculation reflects sympathetic tone, we hypothesized that baseline cutaneous microcirculation in fingers, as detected by laser Doppler flowmetry (LDF), differs among patients with mild cognitive impairment (MCI), AD, and CID. As light therapy is one of the adjunctive treatments for AD and CID, we designed a randomized controlled cross-over trial of light therapy through eyes for 12 weeks with red light as treatment and green light as control limb, and examined if light therapy has an impact on cutaneous microcirculation. Before light therapy, patients with AD had significantly lower baseline cutaneous perfusion than those with CID in left and right first to fourth fingers. After red light therapy, however, cutaneous perfusion of fingers in CID patients significantly decreased (right fingers, before vs. after = 227.25 ± 62.00 vs. 162.00 ± 49.34, p = 0.007; left fingers, before vs. after = 228.99 ± 58.80 vs. 177.41 ± 59.41, p = 0.003) while cutaneous perfusion of fingers in CID patients did not significantly change after green light therapy. Light therapy with red light also significantly increased cutaneous finger perfusion in patients with AD (right fingers, before vs. after = 130.13 ± 49.82 vs. 172.38 ± 38.32, p = 0.043). Our results suggest that cutaneous perfusion is a useful tool to detect sympathetic dysfunction in patients with CID and AD, and that light therapy with red light is a potential therapeutic intervention to reverse impaired sympathetic function in patients with CID and patients with AD.

Impact of Cutaneous Blood Flow on NIR-DCS Measures of Skeletal Muscle Blood Flow Index

Near-infrared diffuse correlation spectroscopy (NIR-DCS) is an optical technique for estimating relative changes in skeletal muscle perfusion during exercise, but may be affected by changes in cutaneous blood flow, as photons emitted by the laser must first pass through the skin. Accordingly, the purpose of this investigation was to examine how increased cutaneous blood flow affects NIR-DCS blood flow index (BFI) at rest and during exercise using a passive whole-body heating protocol that increases cutaneous, but not skeletal muscle, perfusion in the uncovered limb. BFI and cutaneous perfusion (laser Doppler flowmetry) were assessed in 15 healthy young subjects before (e.g., rest) and during 5-minutes of moderate-intensity hand-grip exercise in normothermic conditions and after cutaneous blood flow was elevated via whole-body heating. Hyperthermia significantly increased both cutaneous perfusion (~7.3-fold; p≤0.001) and NIR-DCS BFI (~4.5-fold; p≤0.001). Although relative BFI (i.e., fold-change above baseline) exhibited a typical exponential increase in muscle perfusion during normothermic exercise (2.81±0.95), there was almost no change in BFI during hyperthermic exercise (1.43±0.44). A subset of 8 subjects were subsequently treated with intradermal injection of botulinum toxin-A (Botox) to block heating-induced elevations in cutaneous blood flow, which 1) nearly abolished the hyperthermia-induced increase in BFI, and 2) restored BFI kinetics during hyperthermic exercise to values that were not different from normothermic exercise (p=0.091). Collectively, our results demonstrate that cutaneous blood flow can have a substantial, detrimental impact on NIR-DCS estimates of skeletal muscle perfusion and highlight the need for technical and/or pharmacological advancements to overcome this issue moving forward.

Abdominal Cutaneous Thermography and Perfusion Mapping after Caesarean Section: A Scoping Review

Introduction: Caesarean section (CS) is the most prevalent surgical procedure in women. The incidence of surgical site infection (SSI) after CS remains high but recent observations of CS wounds using infrared thermography has shown promise for the technique in SSI prognosis. Although thermography is recognised as a ‘surrogate’ of skin perfusion, little is known of the relationship between skin temperature and skin perfusion in the context of wound healing. Aim: To assess the extent of literature regarding the application of infrared thermography and mapping of abdominal cutaneous perfusion after CS. Methods: Wide eligibility criteria were used to capture all relevant studies of any design, published in English, and addressing thermal imaging or skin perfusion mapping of the abdominal wall. The CINAHL and MEDLINE databases were searched, with two independent reviewers screening the title and abstracts of all identified citations, followed by full-text screening of relevant studies. Data extraction from included studies was undertaken using a pre-specified data extraction chart. Data were tabulated and synthesised in narrative format. Results: From 83 citations identified, 18 studies were considered relevant. With three additional studies identified from the reference lists, 21 studies were screened via full text. None of the studies reported thermal imaging and cutaneous perfusion patterns of the anterior abdominal wall. However, two observational studies partially met the inclusion criteria. The first explored analysis methodologies to ‘interrogate’ the abdominal thermal map. A specific thermal signature (‘cold spots’) was identified as an early ‘flag’ for SSI risk. A second study, by the same authors, focusing on obesity (a known risk factor for SSI after CS) showed that a 1 °C lower abdominal skin temperature led to a 3-fold odds of SSI. Conclusion: There is a significant gap in knowledge on how to forewarn of wound complications after CS. By utilising the known association between skin temperature and blood flow, thermographic assessment of the wound and adjacent thermal territories has potential as a non-invasive, independent, imaging option with which to identify tissue ‘at risk’. By identifying skin ‘hot’ or ‘cold’ spots, commensurate with high or low blood flow regions, there is potential to shed light on the underlying mechanisms leading to infective and non-infective wound complications.

Association of remote imaging photoplethysmography and cutaneous perfusion in volunteers

Remote imaging photoplethysmography (iPPG) senses the cardiac pulse in outer skin layers and is responsive to mean arterial pressure and pulse pressure in critically ill patients. Whether iPPG is sufficiently sensitive to monitor cutaneous perfusion is not known. This study aimed at determining the response of iPPG to changes in cutaneous perfusion measured by Laser speckle imaging (LSI). Thirty-seven volunteers were engaged in a cognitive test known to evoke autonomic nervous activity and a Heat test. Simultaneous measurements of iPPG and LSI were taken at baseline and during cutaneous perfusion challenges. A perfusion index (PI) was calculated to assess iPPG signal strength. The response of iPPG to the challenges and its relation to LSI were determined. PI of iPPG significantly increased in response to autonomic nervous stimuli and to the Heat test by 5.8% (p = 0.005) and 11.1% (p < 0.001), respectively. PI was associated with LSI measures of cutaneous perfusion throughout experiments (p < 0.001). iPPG responses to study task correlated with those of LSI (r = 0.62, p < 0.001) and were comparable among subjects. iPPG is sensitive to autonomic nervous activity in volunteers and is closely associated with cutaneous perfusion.

Contact-Free Optical Assessment of Changes in the Chest Wall Perfusion after Coronary Artery Bypass Grafting by Imaging Photoplethysmography

Imaging photoplethysmography (iPPG) is a contact-free monitoring of the cutaneous blood volume pulse by RGB (red-green-blue) cameras. It detects vital parameters from skin areas and is associated to cutaneous perfusion. This study investigated the use of iPPG to quantify changes in cutaneous perfusion after major surgery. Patients undergoing coronary artery bypass grafting (CABG) were scanned before surgery and in three follow-up measurements. Using an industrial-grade RGB camera and usual indoor lighting, a contact-free imaging plethysmogram from the chest was obtained. Changes of the iPPG signal strength were evaluated in view of both the operation itself as well as the unilateral preparation of the internal thoracic artery (ITA) for coronary artery grafting, which is the main blood source of the chest wall. iPPG signal strength globally decreased after surgery and recovered partially during the follow up measurements. The ITA preparation led to a deeper decrease and an attenuated recovery of the iPPG signal strength compared to the other side of the chest wall. These results comply with the expected changes of cutaneous perfusion after CABG using an ITA graft. iPPG can be used to assess cutaneous perfusion and its global changes after major surgery as well as its local changes after specific surgical procedures.

Heat shock protein 90 contributes to cutaneous vasodilation through activating nitric oxide synthase in young male adults exercising in the heat

While the mechanisms underlying the control of cutaneous vasodilation have been extensively studied, there remains a lack of understanding of the different factors that may modulate cutaneous perfusion during an exercise-induced heat stress. We evaluated the hypothesis that heat shock protein 90 (HSP90) contributes to the heat loss response of cutaneous vasodilation via the activation of nitric oxide synthase (NOS) during exercise in the heat. In 11 young males (25 ± 5 yr), cutaneous vascular conductance (CVC) was measured at four forearm skin sites that were continuously treated with 1) lactated Ringer solution (control), 2) NOS inhibition with 10 mM NG-nitro-l-arginine methyl ester (l-NAME), 3) HSP90 inhibition with 178 μM geldanamycin, or 4) a combination of 10 mM l-NAME and 178 μM geldanamycin. Participants rested in a moderate heat stress (35°C) condition for 70 min. Thereafter, they performed a 50-min bout of moderate-intensity cycling (~52% V̇o2peak) followed by a 30-min recovery period. We showed that NOS inhibition attenuated CVC (~40–50%) relative to the control site during pre- and postexercise rest in the heat ( P ≤ 0.05); however, no effect of HSP90 inhibition was observed ( P > 0.05). During exercise, we observed an attenuation of CVC with the separate inhibition of NOS (~40–50%) and HSP90 (~15–20%) compared with control (both P ≤ 0.05). However, the effect of HSP90 inhibition was absent in the presence of the coinhibition of NOS ( P > 0.05). We show that HSP90 contributes to cutaneous vasodilation in young men exposed to the heat albeit during exercise only. We also show that the HSP90 contribution is due to NOS-dependent mechanisms. NEW & NOTEWORTHY We show that heat shock protein 90 functionally contributes to the heat loss response of cutaneous vasodilation during exercise in the heat, and this response is mediated through the activation of nitric oxide synthase. Therefore, interventions that may activate heat shock protein 90 may facilitate an increase in heat dissipation through an augmentation of cutaneous perfusion. In turn, this may attenuate or reduce the increase in core temperature and therefore the level of heat strain.

Can Extravasation Injury Cause Subcutaneous Compartment Syndrome of the Hand?

Background: Compartment syndrome of the hand is a well-described phenomenon with potentially devastating consequences. Although numerous mechanisms have been proposed, the extravasation of peripheral intravenous (IV) fluids remains a relatively rare etiology. Objective: Surgical dogma mandates emergent decompressive fasciotomies in the presence of hand dysfunction and impending tissue loss from supraphysiologic compartment pressures. The role of the subcutaneous space in acute compartment syndrome remains unclear. Methods: In this report, we present a case of a dorsal hand IV extravasation leading to an acute compartment syndrome of the subcutaneous space. Results: An emergent skin-only incision was used for decompression, with immediate improvement in symptoms and no long-term adverse sequelae. Discussion: The subcutaneous space appears capable of sustaining supraphysiologic pressures that impair cutaneous perfusion. This closed anatomic space can be readily decompressed, resulting in rapid improvement in soft tissue perfusion. However, its role in contributing to acute compartment syndrome of the hand requires further research. Conclusion: We propose consideration of the subcutaneous space as a distinct hand compartment and advocate selective compartment release when prudent.

Performance evaluation of Cryo Laser Phoresis technique as biophysical method to promote diclofenac sodium cutaneous perfusion

ABSTRACT Aiming to alter and/or improve permeation of active compounds in the skin, many strategies have been developed, including biophysical methods. One of the physical absorption techniques, currently known as Cryo Laser Phoresis (CLP), consists of an apparatus that emits radiation on polar or nonpolar molecules of the active substance, resulting in faster penetration when in comparison to the standard topical application. The goal of this work was to evaluate the efficacy of a method that proposes to increase cutaneous permeation of diclofenac sodium by using CLP technique. The influence on permeation was evaluated ex vivo, using Franz cell and human skin obtained from cosmetic surgery. The results were evaluated using statistical methods and data exploratory analysis: clusters, k-means and Principal Component Analysis. The results showed a larger increase in the concentration of diclofenac sodium in the dermis with the use of laser. In all samples (with or without laser application) it was observed that skin surface showed an amount of diclofenac sodium and that there was no active passage to the receptor liquid, suggesting that diclofenac sodium was not absorbed. These results indicate that CLP, when used under the conditions described in this study, is able to increase diclofenac sodium penetration and its retention into deeper layers.

Can intradermal administration of angiotensin II influence human heat loss responses during whole body heat stress?

It is unclear if angiotensin II, which can increase the production of reactive oxygen species (oxidative stress), modulates heat loss responses of cutaneous blood flow and sweating. We tested the hypothesis that angiotensin II-induced increases in oxidative stress impair cutaneous perfusion and sweating during rest and exercise in the heat. Eleven young (24 ± 4 yr) healthy adults performed two 30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C). The first and second exercises were followed by a 20- and 40-min recovery. Four microdialysis fibers were placed in the forearm skin for continuous administration of either: 1) lactated Ringer (control), 2) 10 μM angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10 μM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser-Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule) were evaluated at each skin site. Compared with control, angiotensin II reduced both CVC and sweating at baseline resting and during each recovery in the heat (all P < 0.05). However, during both exercise bouts, there were no differences in CVC or sweating between the treatment sites (all P > 0.05). When ascorbate was coinfused with angiotensin II, the effect of angiotensin II on sweating was abolished (all P > 0.05); however, its effect on CVC at baseline resting and during each recovery remained intact (all P < 0.05). We show angiotensin II impairs cutaneous perfusion independent of oxidative stress, while it impairs sweating through increasing oxidative stress during exposure to an ambient heat stress before and following exercise.