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Microcirculation in Health and Disease

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A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Physiology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 47686

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Special Issue Editors

Prof. Dr. Henrique Silva

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Guest Editor

1. CBIOS - Research Center for Biosciences & Health Technologies, Universidade Lusófona de Humanidades e Tecnologias, Portugal
2. Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Interests: microcirculation; laser Doppler flowmetry; photoplethysmography; wavelet transform; transcutaneous gasimetry; signal processing; experimental dermatology

Dr. Helena Lenasi

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Guest Editor

Faculty of Medicine, Institute of Physiology, University of Ljubljana, Ljubljana, Slovenia
Interests: cardiovascular physiology; microcirculation; sports physiology; endurance; endothelium; laser doppler; iontophoresis; wavelet analysis; heart rate variability; hyperglycemia; oral glucose tolerance test; cardiopulmonary exercise testing (CPET); VO₂ max
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Prof. Dr. Markos Klonizakis

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Lifestyle Exercise and Nutrition Improvement (LENI) Research Group, Department of Nursing and Midwifery, Sheffield Hallam University, Sheffield S1 1WB, UK
Interests: lifestyle interventions in clinical and healthy-but-sedentary populations; randomized controlled trial; cardiovascular; exercise programme on pain and fatigue outcomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microcirculation plays a pivotal role in the coordination of cardiovascular function, from regulation of rheology and hemostasis, to the control of perfusion and immune response. Microcirculation dysfunction is an early hallmark of several cardiovascular and metabolic diseases, preceding clinical manifestations by several years. Therefore, understanding microcirculation in normal and pathological conditions is essential for assessing cardiovascular risk as well as for the adoption of adequate preventive and therapeutic measures to be taken. Assessment of microcirculation is challenging, especially in humans, with most data coming from semiquantitative techniques. However, methodology to assess microcirculation keeps evolving, allowing the exploration of new avenues from new recording technologies to innovative signal processing algorithms. This Special Issue will present new experimental and clinical results making use of classic and modern methodology to explore the roles of microcirculation in normal physiology and in cardiovascular and metabolic diseases.

Prof. Dr. Henrique Silva
Prof. Dr. Helena Lenasi
Prof. Dr. Markos Klonizakis
Guest Editors

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Keywords

microcirculation
cardiovascular dysfunction
metabolic diseases
cardiovascular diseases
endothelial dysfunction
laser Doppler flowmetry
signal processing algorithms

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Published Papers (11 papers)

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Research

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17 pages, 11736 KiB

Open AccessArticle

Oral Glucose Load and Human Cutaneous Microcirculation: An Insight into Flowmotion Assessed by Wavelet Transform

by Henrique Silva, Jernej Šorli and Helena Lenasi

Biology 2021, 10(10), 953; https://doi.org/10.3390/biology10100953 - 23 Sep 2021

Cited by 5 | Viewed by 2161

Abstract

Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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17 pages, 13562 KiB

Open AccessArticle

Intermittent Sequential Pneumatic Compression Improves Coupling between Cerebral Oxyhaemoglobin and Arterial Blood Pressure in Patients with Cerebral Infarction

by Wenhao Li, Gongcheng Xu, Congcong Huo, Hui Xie, Zeping Lv, Haihong Zhao and Zengyong Li

Biology 2021, 10(9), 869; https://doi.org/10.3390/biology10090869 - 4 Sep 2021

Cited by 6 | Viewed by 2616

Abstract

This study aims to explore the effect of intermittent sequential pneumatic compression (ISPC) intervention on the coupling relationship between arterial blood pressure (ABP) and changes in oxyhaemoglobin (Δ [O₂Hb]). The coupling strength between the two physiological systems was estimated using a coupling function based on dynamic Bayesian inference. The participants were 22 cerebral infarction patients and 20 age- and sex-matched healthy controls. Compared with resting state, the coupling strength from ABP to Δ [O₂Hb] oscillations was significantly lower in the bilateral prefrontal cortex (PFC), sensorimotor cortex (SMC), and temporal lobe cortex (TLC) during the ISPC intervention in cerebral infarction patients in interval II. Additionally, the coupling strength was significantly lower in the bilateral SMC in both groups in interval III. These findings indicate that ISPC intervention may facilitate cerebral circulation in the bilateral PFC, SMC, and TLC in cerebral infarction patients. ISPC may promote motor function recovery through its positive influences on motor-related networks. Furthermore, the coupling between Δ [O₂Hb] and ABP allows non-invasive assessments of autoregulatory function to quantitatively assess the effect of rehabilitation tasks and to guide therapy in clinical situations. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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22 pages, 1337 KiB

Open AccessArticle

Effects of n-3 Polyunsaturated Fatty Acid-Enriched Hen Egg Consumption on the Inflammatory Biomarkers and Microvascular Function in Patients with Acute and Chronic Coronary Syndrome—A Randomized Study

by Željka Breškić Ćurić, Ana Marija Masle, Aleksandar Kibel, Kristina Selthofer-Relatić, Ana Stupin, Zrinka Mihaljević, Ivana Jukić, Marko Stupin, Anita Matić, Nataša Kozina, Petar Šušnjara, Brankica Juranić, Nikolina Kolobarić, Vatroslav Šerić and Ines Drenjančević

Biology 2021, 10(8), 774; https://doi.org/10.3390/biology10080774 - 14 Aug 2021

Cited by 7 | Viewed by 2732

Abstract

This study aimed to test the effect of n-3 polyunsaturated fatty acid (PUFA)-enriched hen egg consumption on serum lipid and free fatty acid profiles, inflammatory and oxidative stress biomarkers, and microvascular reactivity in patients with coronary artery disease (CAD). Forty CAD patients participated in this study. Of those, 20 patients had acute CAD (Ac-CAD), and 20 patients had chronic CAD (Ch-CAD). The control group (N = 20) consumed three regular hen eggs/daily (249 mg n-3 PUFAs/day), and the n-3 PUFAs group (N = 20) consumed three n-3 PUFA-enriched hen eggs/daily (1053 g n-3 PUFAs/day) for 3 weeks. Serum n-3 PUFA concentration significantly increased (in all CAD patients), while LDL cholesterol and IL-6 (in Ac-CAD patients), and hsCRP and IL-1a (in all CAD patients) significantly decreased in the n-3 PUFAs group. Glutathione peroxidase (GPx) activity significantly decreased, and forearm skin microvascular reactivity in response to vascular occlusion (postocclusive reactive hyperemia (PORH)) remained unchanged in both the n-3 PUFAs and control groups in total CAD, Ac-CAD, and Ch-CAD patients. Potentially, n-3 PUFA-enriched hen eggs can change the free fatty acid profile to a more favorable lower n6/n3 ratio, and to exhibit mild anti-inflammatory effects but not to affect microvascular reactivity in CAD patients. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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11 pages, 907 KiB

Open AccessArticle

Mechanisms of Venoarteriolar Reflex in Type 2 Diabetes with or without Peripheral Neuropathy

by Cécile Reynès, Antonia Perez-Martin, Houda Ennaifer, Henrique Silva, Yannick Knapp and Agnès Vinet

Biology 2021, 10(4), 333; https://doi.org/10.3390/biology10040333 - 15 Apr 2021

Cited by 4 | Viewed by 2491

Abstract

The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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15 pages, 10828 KiB

Open AccessArticle

3D Imaging and Quantitative Characterization of Mouse Capillary Coronary Network Architecture

by Nabil Nicolas and Etienne Roux

Biology 2021, 10(4), 306; https://doi.org/10.3390/biology10040306 - 7 Apr 2021

Cited by 8 | Viewed by 3473

Abstract

Characterization of the cardiac capillary network structure is of critical importance to understand the normal coronary functional properties and coronary microvascular diseases. The aim of our study was to establish an accessible methodology for 3D imaging and 3D processing to quantitatively characterize the capillary coronary network architecture in mice. Experiments were done on C57BL/6J mice. 3D imaging was performed by light sheet microscopy and confocal microscopy on iDISCO+ optical cleared hearts after labelling of the capillary endothelium by lectin injection. 3D images were processed with the open source software ImageJ. Non-visual image segmentation was based of the frequency distribution of the voxel greyscale values, followed by skeletonization and distance mapping. Capillary networks in left and right ventricles and septum were characterized by the volume network density, the fractal dimension, the number of segments and nodes and their ratio, the total network length, and the average length, diameter, and tortuosity of the segments. Scale-dependent parameter values can be impacted by the resolution limit of the 3D imaging technique. The proposed standardized methodology for 3D image processing is easily accessible for a biologist in terms of investment and difficulty level, and allows the quantification of the 3D capillary architecture and its statistical comparison in different conditions. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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19 pages, 1475 KiB

Open AccessArticle

A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

by Leoné Malan, Mark Hamer, Roland von Känel, Roelof D. van Wyk, Anne E. Sumner, Peter M. Nilsson, Gavin W. Lambert, Hendrik S. Steyn, Casper J. Badenhorst and Nico T. Malan

Biology 2021, 10(2), 162; https://doi.org/10.3390/biology10020162 - 18 Feb 2021

Cited by 6 | Viewed by 3710

Abstract

Type 3 diabetes (T3D) accurately reflects that dementia, e.g., Alzheimer’s disease, represents insulin resistance and neurodegeneration in the brain. Similar retinal microvascular changes were observed in Alzheimer’s and chronic stressed individuals. Hence, we aimed to show that chronic stress relates to T3D dementia signs and retinopathy, ultimately comprising a Stress syndrome prototype reflecting risk for T3D and stroke. A chronic stress and stroke risk phenotype (Stressed) score, independent of age, race or gender, was applied to stratify participants (N = 264; aged 44 ± 9 years) into high stress risk (Stressed, N = 159) and low stress risk (non-Stressed, N = 105) groups. We determined insulin resistance using the homeostatic model assessment (HOMA-IR), which is interchangeable with T3D, and dementia risk markers (cognitive executive functioning (cognitive_exe-func); telomere length; waist circumference (WC), neuronal glia injury; neuron-specific enolase/NSE, S100B). Retinopathy was determined in the mydriatic eye. The Stressed group had greater incidence of HOMA-IR in the upper quartile (≥5), larger WC, poorer cognitive_exe-func control, shorter telomeres, consistently raised neuronal glia injury, fewer retinal arteries, narrower arteries, wider veins and a larger optic cup/disc ratio (C/D) compared to the non-Stressed group. Furthermore, of the stroke risk markers, arterial narrowing was related to glaucoma risk with a greater C/D, whilst retinal vein widening was related to HOMA-IR, poor cognitive_exe-func control and neuronal glia injury (Adjusted R² 0.30; p ≤ 0.05). These associations were not evident in the non-Stressed group. Logistic regression associations between the Stressed phenotype and four dementia risk markers (cognitive_exe-func, telomere length, NSE and WC) comprised a Stress syndrome prototype (area under the curve 0.80; sensitivity/specificity 85%/58%; p ≤ 0.001). The Stress syndrome prototype reflected risk for HOMA-IR (odds ratio (OR) 7.72) and retinal glia ischemia (OR 1.27) and vein widening (OR 1.03). The Stressed phenotype was associated with neuronal glia injury and retinal ischemia, potentiating glaucoma risk. The detrimental effect of chronic stress exemplified a Stress syndrome prototype reflecting risk for type 3 diabetes, neurodegeneration and ischemic stroke. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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Review

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27 pages, 12109 KiB

Open AccessReview

The Role of Food Supplementation in Microcirculation—A Comprehensive Review

by António Raposo, Ariana Saraiva, Fernando Ramos, Conrado Carrascosa, Dele Raheem, Rita Bárbara and Henrique Silva

Biology 2021, 10(7), 616; https://doi.org/10.3390/biology10070616 - 2 Jul 2021

Cited by 13 | Viewed by 6498 | Correction

Abstract

(1) Background: Cardiovascular disease (CVD) is a major public health concern worldwide and a key cause of morbidity and mortality in developed countries. Accumulating evidence shows that several CVD forms are characterized by significant microcirculatory dysfunction, which may both cause and be caused by macrovascular disease, often preceding clinical manifestations by several years. Therefore, interest in exploring food supplements to prevent and restore microcirculation has grown. Given the continuous need to expand the available therapeutic arsenal for CVD, the food supplements market has recently grown and is expected to continue growing. (2) Methods: We provide an authoritative up-to-date comprehensive review of the impact of food supplementation on microcirculation by analyzing the European and American legal food supplements framework and the importance of food safety/food quality in this industry. We review the main literature about food bioactive compounds with a focus on microcirculation and some main food supplements with proven benefits. (3) Results: Despite a lack of scientific evidence, diet and microcirculatory function are clearly connected. The main food supplement examples in the literature with potential beneficial effects on microcirculation are: Ruscus aculeatus L., Centella asiatica L., Ginkgo biloba L., Salvia miltiorrhiza Bunge, Crataegus spp., Ginseng, Mangifera indica L., Aesculus hippocastanum L., Hamamelis virginiana L., and Vitis vinifera L. (4) Conclusions: Further clinical trials are necessary to better explore the effects of these food supplements. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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27 pages, 362 KiB

Open AccessReview

Tobacco Use and Periodontal Disease—The Role of Microvascular Dysfunction

by Henrique Silva

Biology 2021, 10(5), 441; https://doi.org/10.3390/biology10050441 - 17 May 2021

Cited by 34 | Viewed by 8503

Abstract

Periodontal disease consists in highly prevalent wide-ranging inflammatory conditions that affect the supporting apparatus of teeth. Tobacco use is the most important risk factor for periodontal disease as it increases disease severity and periodontal surgery complications. Tobacco use is harmful for the vasculature by causing microvascular dysfunction, which is known to negatively affect periodontal disease. To the author’s knowledge this paper is the first comprehensive review on the mechanisms by which tobacco use affects oral microcirculation and impacts the pathophysiology of periodontal disease. In healthy subjects, acute nicotine administration or tobacco use (smoking/smokeless forms) increases the blood flow in the oral mucosa due to local irritation and increased blood pressure, which overcome neural- and endocrine-mediated vasoconstriction. Chronic tobacco smokers display an increased gingival microvascular density, which is attributed to an increased capillary recruitment, however, these microcirculatory units show higher tortuosity and lower caliber. These morphological changes, together with the repetitive vasoconstrictive insults, contribute to lower gingival perfusion in chronic smokers and do not completely regress upon smoking cessation. In periodontal disease there is considerable gingival inflammation and angiogenesis in non-smokers which, in chronic smokers, are considerably suppressed, in part due to local immune suppression and oxidative stress. Tobacco exposure, irrespective of the form of use, causes long-term microvascular dysfunction that increases the risk of complications due to the natural disease course or secondary therapeutic strategies. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

38 pages, 1431 KiB

Open AccessReview

The Vascular Effects of Isolated Isoflavones—A Focus on the Determinants of Blood Pressure Regulation

by Henrique Silva

Biology 2021, 10(1), 49; https://doi.org/10.3390/biology10010049 - 12 Jan 2021

Cited by 23 | Viewed by 5175

Abstract

Isoflavones are phytoestrogen compounds with important biological activities, including improvement of cardiovascular health. This activity is most evident in populations with a high isoflavone dietary intake, essentially from soybean-based products. The major isoflavones known to display the most important cardiovascular effects are genistein, daidzein, glycitein, formononetin, and biochanin A, although the closely related metabolite equol is also relevant. Most clinical studies have been focused on the impact of dietary intake or supplementation with mixtures of compounds, with only a few addressing the effect of isolated compounds. This paper reviews the main actions of isolated isoflavones on the vasculature, with particular focus given to their effect on the determinants of blood pressure regulation. Isoflavones exert vasorelaxation due to a multitude of pathways in different vascular beds. They can act in the endothelium to potentiate the release of NO and endothelium-derived hyperpolarization factors. In the vascular smooth muscle, isoflavones modulate calcium and potassium channels, leading to hyperpolarization and relaxation. Some of these effects are influenced by the binding of isoflavones to estrogen receptors and to the inhibition of specific kinase enzymes. The vasorelaxation effects of isoflavones are mostly obtained with plasma concentrations in the micromolar range, which are only attained through supplementation. This paper highlights isolated isoflavones as potentially suitable alternatives to soy-based foodstuffs and supplements and which could enlarge the current therapeutic arsenal. Nonetheless, more studies are needed to better establish their safety profile and elect the most useful applications. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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19 pages, 984 KiB

Open AccessEditor’s ChoiceReview

Imaging of the Intestinal Microcirculation during Acute and Chronic Inflammation

by Kayle Dickson, Hajer Malitan and Christian Lehmann

Biology 2020, 9(12), 418; https://doi.org/10.3390/biology9120418 - 26 Nov 2020

Cited by 11 | Viewed by 6311

Abstract

Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly death. Microcirculation may be evaluated in superficial tissues in patients using video microscopy devices, but these techniques do not allow the assessment of intestinal microcirculation. The gold standard for the experimental evaluation of intestinal microcirculation is intravital microscopy, a technique that allows for the in vivo examination of many pathophysiological processes including leukocyte-endothelial interactions and capillary blood flow. This review provides an overview of changes in the intestinal microcirculation in various acute and chronic inflammatory conditions. Acute conditions discussed include local infections, severe acute pancreatitis, necrotizing enterocolitis and sepsis. Inflammatory bowel disease and irritable bowel syndrome are included as examples of chronic conditions of the intestine. Full article

(This article belongs to the Special Issue Microcirculation in Health and Disease)

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