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Biomedicines
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Microcirculation in Health and Diseases
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Microcirculation in Health and Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 6706

Special Issue Editor

Dr. Jolanta Neubauer-Geryk

E-Mail Website
Guest Editor
Clinical Physiology Unit, Medical Simulation Centre, Medical University of Gdańsk, Gdansk, Poland
Interests: endothelial dysfunction; microcirculation; macrocirculation; diabetes mellitus; cardiovascular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microcirculation accounts for approximately 99% of all adult human blood vessels, and mediates, both structurally and functionally, between the arterial and venous parts of the cardiovascular system. It encompasses vessels narrower than 150 μm in diameter—i.e., arteries, small veins, lymphatic and arteriovenous vessels, and lymphatic and arteriovenous anastomoses—which constitute the microcirculatory unit. According to a definition based on vessel diameter and vascular muscle response to pressure difference, all vessels that are constricted by increased blood pressure form the microcirculatory unit.

Microcirculation is responsible for the exchange of nutrients and metabolites between blood and tissues, protecting the capillary network from large hydrostatic pressure fluctuations, and reducing peripheral vascular resistance. Capillaries consist of endothelial cells surrounded by pericytes and basement membranes, while arterioles have an additional thick layer of smooth muscle cells (media).

Endothelial cells, as a selective barrier between blood and surrounding tissues, are an important part of the lining of the microcirculation, and any endothelial impairment or dysfunction plays a key role in the development, progression or exacerbation of microvascular dysfunction, affecting various organ systems and their physiological processes.

Microvascular dysfunction is therefore considered to represent a generalized process that plays an important role in cardiovascular and metabolic diseases such as obesity, hypertension and diabetes, sepsis, and even cardiac transplant dysfunction. That is why this Special Issue of Biomedicines entitled “Microcirculation in Health and Diseases” will focus on the latest research on the pathogenesis, early diagnosis, or treatment of microcirculatory disorders, regardless of their location. Original research and review articles covering both conventional and innovative technologies and spanning both in vitro and in vivo studies are all welcome.

Dr. Jolanta Neubauer-Geryk
Guest Editor

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Keywords

  • microcirculation
  • skin microcirculation
  • microcirculatory disorders
  • endothelial dysfunction
  • therapies
  • human

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Published Papers (7 papers)

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Research

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9 pages, 614 KiB  
Communication
What Remote PPG Oximetry Tells Us about Pulsatile Volume?
by Gennadi Saiko
Biomedicines 2024, 12(8), 1784; https://doi.org/10.3390/biomedicines12081784 - 6 Aug 2024
Viewed by 595
Abstract
While pulse oximetry using remote photoplethysmography (rPPG) is used in medicine and consumer health, sound theoretical foundations for this methodology are not established. Similarly to traditional pulse oximetry, rPPG oximetry uses two wavelengths to calculate the tissue oxygenation using the so-called ratio-of-ratios, R [...] Read more.
While pulse oximetry using remote photoplethysmography (rPPG) is used in medicine and consumer health, sound theoretical foundations for this methodology are not established. Similarly to traditional pulse oximetry, rPPG oximetry uses two wavelengths to calculate the tissue oxygenation using the so-called ratio-of-ratios, R. However, the relationship between R and tissue oxygenation has not been derived analytically. As such, rPPG oximetry relies mostly on empirical methods. This article aimed to build theoretical foundations for pulse oximetry in rPPG geometry. Using the perturbation approach in diffuse approximation for light propagation in tissues, we obtained an explicit expression of the AC/DC ratio for the rPPG signal. Based on this ratio, the explicit expression for “ratio-of-ratios” was obtained. We have simulated the dependence of “ratio-of-ratios” on arterial blood saturation across a wide range (SaO2 = 70–100%) for several commonly used R/IR light sources (660/780, 660/840, 660/880, and 660/940 nm) and found that the obtained relationship can be modeled by linear functions with an extremely good fit (R2 = 0.98–0.99) for all considered R/IR pairs. Moreover, the location of the pulsatile volume can be extracted from rPPG data. From experimental data, we found that the depth of blood pulsations in the human forehead can be estimated as 0.6 mm on the arterial side, which points to the papillary dermis/subpapillary vascular plexus origin of the pulsatile volume. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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15 pages, 4060 KiB  
Article
Transitions from Aerobic to Anaerobic Metabolism and Oxygen Debt during Elective Major and Emergency Non-Cardiac Surgery
by Nikolaos Papagiannakis, Dimitrios Ragias, Nicoleta Ntalarizou, Eleni Laou, Aikaterini Kyriakaki, Theodoros Mavridis, Amir Vahedian-Azimi, Minas Sakellakis and Athanasios Chalkias
Biomedicines 2024, 12(8), 1754; https://doi.org/10.3390/biomedicines12081754 - 5 Aug 2024
Viewed by 877
Abstract
Introduction: Intraoperative hemodynamic and metabolic optimization of both the high-risk surgical patients and critically ill patients remains challenging. Reductions in oxygen delivery or increases in oxygen consumption can initiate complex cellular processes precipitating oxygen debt (OXD). Methods: This study tested the hypothesis that [...] Read more.
Introduction: Intraoperative hemodynamic and metabolic optimization of both the high-risk surgical patients and critically ill patients remains challenging. Reductions in oxygen delivery or increases in oxygen consumption can initiate complex cellular processes precipitating oxygen debt (OXD). Methods: This study tested the hypothesis that intraoperative changes in sublingual microcirculatory flow reflect clinically relevant transitions from aerobic to anaerobic metabolism (TRANAM). We included patients undergoing elective major and emergency non-cardiac surgery. Macro- and microcirculatory variables, oxygen extraction, and transitions of metabolism were assessed in both cohorts. Results: In the elective group, OXD was progressively increased over time, with an estimated 2.24 unit increase every 30 min (adjusted p < 0.001). Also, OXD was negatively correlated with central venous pressure (ρ = −0.247, adjusted p = 0.006) and positively correlated with stroke volume variation (ρ = 0.185, adjusted p = 0.041). However, it was not significantly correlated with sublingual microcirculation variables. In the emergency surgery group, OXD increased during the first two intraoperative hours and then gradually decreased until the end of surgery. In that cohort, OXD was positively correlated with diastolic arterial pressure (ρ = 0.338, adjpatients and the critically ill patients remains challengingsted p = 0.015). Also, OXD was negatively correlated with cardiac index (ρ = −0.352, adjusted p = 0.003), Consensus Proportion of Perfused Vessels (PPV) (ρ = −0.438, adjusted p < 0.001), and Consensus PPV (small) (ρ = −0.434, adjusted p < 0.001). Conclusions: TRANAM were evident in both the elective major and emergency non-cardiac surgery cohorts independent of underlying alterations in the sublingual microcirculation. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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22 pages, 168912 KiB  
Article
Heterogeneous Patterns of Endothelial NF-κB p65 and MAPK c-Jun Activation, Adhesion Molecule Expression, and Leukocyte Recruitment in Lung Microvasculature of Mice with Sepsis
by Zhendong Wang, Erna-Zulaikha Dayang, Peter J. Zwiers, Martha L. Hernandez Garcia, Matthijs Luxen, Matijs van Meurs, Jill Moser, Jan A. A. M. Kamps and Grietje Molema
Biomedicines 2024, 12(8), 1672; https://doi.org/10.3390/biomedicines12081672 - 26 Jul 2024
Viewed by 766
Abstract
Background: Sepsis is an uncontrolled systemic inflammatory response to an infection that can result in acute failure of the function of the lung called acute respiratory distress syndrome. Leukocyte recruitment is an important hallmark of acute lung failure in patients with sepsis. Endothelial [...] Read more.
Background: Sepsis is an uncontrolled systemic inflammatory response to an infection that can result in acute failure of the function of the lung called acute respiratory distress syndrome. Leukocyte recruitment is an important hallmark of acute lung failure in patients with sepsis. Endothelial cells (EC) participate in this process by facilitating tethering, rolling, adhesion, and transmigration of leukocytes via adhesion molecules on their cell surface. In in vivo studies, endothelial nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 and mitogen-activated protein kinase (MAPK) c-Jun intracellular signal transduction pathways were reported to regulate the expression of adhesion molecules. Methods: Mice underwent cecal ligation and puncture (CLP) to induce polymicrobial sepsis and were sacrificed at different time points up to 72 h after sepsis onset. Immunohistochemistry and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine the kinetics of nuclear localization of p65 and c-Jun in EC, expression and location of adhesion molecules E-selectin and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, the extent and location of leukocyte recruitment were assessed based on Ly6G staining of neutrophils, cluster determinant (CD) 3 staining of T lymphocytes, and CD68 staining of macrophages. Results: In all pulmonary microvascular beds, we identified p65 and c-Jun nuclear accumulation in a subset of endothelial cells within the first 24 h after CLP-sepsis initiation. E-selectin protein was expressed in a subset of microvessels at 4 and 7 h after sepsis initiation, while VCAM-1 was expressed in a scattered pattern in alveolar tissue and microvessels, without discernible changes during sepsis development. CLP-induced sepsis predominantly promoted the accumulation of neutrophils and T lymphocytes 4 and 7 h after disease onset. Neutrophil accumulation occurred in all pulmonary microvascular beds, while T lymphocytes were present in alveolar tissue and postcapillary venules. Taken together, nuclear localization of p65 and c-Jun in EC and neutrophil recruitment could be associated with induced E-selectin expression in the pulmonary microvessels in CLP-septic mice at the early stage of the disease. In alveolar capillaries, on the other hand, activation of these molecular pathways and leukocyte accumulation occurred in the absence of E-selectin or VCAM-1. Conclusions: Endothelial activation and leukocyte recruitment in sepsis-induced lung injury are regulated by multiple, heterogeneously controlled mechanisms, which vary depending on the type of microvascular bed involved. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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13 pages, 1211 KiB  
Article
Early Cerebral Microvasculature Impairment and Increased Body Mass Index in Patients with Psoriasis
by Katarzyna Piec, Luiza Marek-Józefowicz, Katarzyna Nadolska, Adam Lemanowicz, Zbigniew Serafin and Grzegorz Kozera
Biomedicines 2024, 12(8), 1627; https://doi.org/10.3390/biomedicines12081627 - 23 Jul 2024
Viewed by 688
Abstract
Psoriasis induces systemic atherosclerosis, but its impact on cerebrovascular function remains unclear. However, stroke prevention must be considered in psoriasis, as it is commonly comorbid with classic cardiovascular risk factors. Thus, the aim of the study is to assess cerebral microvasculature function and [...] Read more.
Psoriasis induces systemic atherosclerosis, but its impact on cerebrovascular function remains unclear. However, stroke prevention must be considered in psoriasis, as it is commonly comorbid with classic cardiovascular risk factors. Thus, the aim of the study is to assess cerebral microvasculature function and its confounders in patients with psoriasis. The study protocol included cerebral autoregulation assessment with measurements of vasomotor reactivity reserve (VMRr) on the middle cerebral arteries with the use of a Transcranial Doppler (TCD) in 50 patients with psoriasis without cerebrovascular events (46; 21–74 years) and 26 healthy controls (41; 29–58 years). Analyses of VMRr relationships with the psoriasis course, comorbidities, inflammatory markers and intima–media thickness (IMT) were performed. The study showed that VMRr was lower (64% vs. 76%, p = 0.001), and the IMT was higher (0.65 vs. 0.52 mm, p = 0.001) in patients compared to controls. The patients were also characterized by a higher body mass index (BMI) and a higher level of Il-6 than the controls (29.14 vs. 25.76 kg/m2, p = 0.004 and 585 vs. 204 pg/mL, p < 0.001, respectively), but only BMI was independently impacting VMRr reduction (p = 0.02). In conclusion, early cerebral microvasculature dysfunction may occur in patients with psoriasis, and its extent is associated with an increase in BMI. Thus, body mass reduction should be strongly recommended for stroke prophylaxis in patients with psoriasis. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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19 pages, 1048 KiB  
Article
The Impact of Disease Duration on Microcirculatory Dysfunction in Young Patients with Uncomplicated Type 1 Diabetes
by Jolanta Neubauer-Geryk, Melanie Wielicka, Magdalena Hoffmann, Małgorzata Myśliwiec and Leszek Bieniaszewski
Biomedicines 2024, 12(5), 1020; https://doi.org/10.3390/biomedicines12051020 - 6 May 2024
Cited by 1 | Viewed by 922
Abstract
This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the [...] Read more.
This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO2_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO2_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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Review

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16 pages, 1736 KiB  
Review
A Triple Mystery of Insidious Organ Failure: Are the Lung, Kidney and Brain All Damaged by the Ageing Pulse?
by Jonathan Stone, Stephen R. Robinson, John Mitrofanis and Daniel M. Johnstone
Biomedicines 2024, 12(9), 1969; https://doi.org/10.3390/biomedicines12091969 - 1 Sep 2024
Viewed by 606
Abstract
This review explores the hypothesis that dementia in several forms, chronic kidney disease and idiopathic pulmonary fibrosis have a common cause in pulse-induced capillary haemorrhage. All three conditions are age-related and characterised by insidious onset, uncertainty about their cause, exacerbation by hypertension, resistance [...] Read more.
This review explores the hypothesis that dementia in several forms, chronic kidney disease and idiopathic pulmonary fibrosis have a common cause in pulse-induced capillary haemorrhage. All three conditions are age-related and characterised by insidious onset, uncertainty about their cause, exacerbation by hypertension, resistance to treatment and the relentlessness of their progression. We argue that the three conditions are the clinical outcomes of damage caused by pulse-induced haemorrhage from capillaries. The damage, first detectable in mid-life, creates first mild and then severe symptoms of cognitive, renal and pulmonary dysfunction. We also review evidence that in all three organs there has developed, by young adulthood, a reserve of tissue that enables them to function well, despite the ‘heartbeat by heartbeat’ damage that accumulates from early mid-life; and that it is when that reserve is exhausted, typically in late age, that symptoms of organ failure emerge and progress. If this common cause can be established, a step will have been taken towards the understanding, treatment and delay of three conditions that have their beginnings in every individual and that, in those who survive other causes of death, become lethal in late age. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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Other

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25 pages, 805 KiB  
Systematic Review
Microvascular Changes during Viral Infections: A Systematic Review of Studies Using Retinal Vessel Diameter Assessments
by Adam Saloň, Patrick De Boever and Nandu Goswami
Biomedicines 2024, 12(7), 1488; https://doi.org/10.3390/biomedicines12071488 - 5 Jul 2024
Viewed by 997
Abstract
Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical [...] Read more.
Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical non-invasive method to assess the structure and function of the retinal microcirculation, a proxy for the microcirculatory system, retinal fundus imaging can be used. We examined the impact of viral infections on retinal vessel diameters and performed a systematic analysis of the literature. Our search was carried out on PubMed using predefined search queries. After a methodological filtering process, we were able to reduce the corpus of 363 publications to 16 studies that met the search parameters. We used a narrative review style to summarise the observations. Six studies covered COVID-19, seven described HIV, and three were included in the subgroup called others, covering viruses, such as Dengue Fever and Crimean–Congo Haemorrhagic Fever. Analysis of the literature showed that viral infections are associated with alterations in the retinal vessels’ vasoactivity. COVID-19 and other infections cause inflammation-associated the vasodilatation of microvasculature as a short-term effect of the infection. Long COVID-19 as well as HIV are the cause of chronic inflammation impacting microvascular morphology via retinal vessel diameter narrowing. The review emphasises the importance of the understudied area of viral infections’ effects on retinal microcirculation. Continuous research in this area is needed to further verify retinal fundus imaging as an innovative tool for the optimal diagnosis of microvascular changes. As changes in the microvasculature precede changes in bigger arteries, the early detection of microvascular changes can go a long way in reducing the morbidity and mortality associated with cardiovascular diseases. Full article
(This article belongs to the Special Issue Microcirculation in Health and Diseases)
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