Microcirculatory and Metabolic Responses during Voluntary Cycle Ergometer Exercise with a Whole-Body Neuromuscular Electrical Stimulation Device

Vigorous exercise increases blood viscosity and may pose a risk of cardiovascular events in patients with cardiovascular diseases. We recently reported that single-use of novel whole-body neuromuscular electrical stimulation (WB-NMES) can be safely applied in healthy subjects without adversely affecting blood fluidity. We performed a crossover study to explore the effectiveness and safety of a hybrid exercise with ergo-bicycle and WB-NMES; 15 healthy volunteers, aged 23–41 years, participated in this study. No arrhythmias were detected during the hybrid exercise and 20 min recovery, and although blood fluidity was transiently exacerbated immediately after both the exercise programs, in vivo parameters in the sublingual and nailfold microcirculation remained unchanged. There was a significant decrease in blood glucose and increase in lactic acid levels immediately after both exercise programs. Even with the same workload as the cycle ergometer exercise, the oxygen intake during the hybrid exercise remained higher than that during the cycle ergometer exercise alone (p < 0.05, r = 0.79, power = 0.81). Both the hybrid and voluntary cycle ergometer exercises transiently exacerbated blood fluidity ex vivo; however, microvascular flow was not adversely affected in vivo.

Endothelial cells and coagulation

Endothelial cells form a monolayer, which lines blood vessels. They are crucially involved in maintaining blood fluidity and providing controlled vascular hemostasis at sites of injury. Thereby endothelial cells facilitate multiple mechanisms, including both procoagulant and anticoagulant, which must be kept in balance. Under physiological conditions, endothelial cells constitute a nonadhesive surface preventing activation of platelets and the coagulation cascade. Multiple fibrinolytic and antithrombotic properties act on their cell surface contributing to the maintenance of blood fluidity. These include platelet inhibition, the heparin-antithrombin III system, tissue factor pathway inhibition, thrombomodulin/protein C system, and fibrinolytic qualities. At sites of vascular damage, platelets react immediately by adhering to the exposed extracellular matrix, followed by platelet-platelet interactions to form a clot that effectively seals the injured vessel wall to prevent excessive blood loss. For solid thrombus formation, functional platelets are essential. In this process, endothelial cells serve as a support surface for formation of procoagulant complexes and clotting. This review gives an overview about the central role of the endothelium as a dynamic lining which controls the complex interplay of the coagulation system with the surrounding cells.

Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has been found in advanced COVID-19. Endothelial cells play a critical role in many physiological processes, such as controlling blood fluidity, leukocyte activation, adhesion, platelet adhesion and aggregation, and transmigration. Therefore, it is reasonable to think that endothelial dysfunction leads to vascular dysfunction, immune thrombosis, and inflammation associated with COVID-19. This article summarizes the association of endothelial dysfunction and SARS-CoV-2 infection and its therapeutic strategies.

Endothelium as a Source and Target of H2S to Improve Its Trophism and Function

The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vascularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease progression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools.

Effects of whole-body neuromuscular electrical stimulation device on hemodynamics, arrhythmia, and sublingual microcirculation

Neuromuscular electrical stimulation has been used to treat cardiovascular diseases and other types of muscular dysfunction. A novel whole-body neuromuscular electrical stimulation (WB-NMES) wearable device may be beneficial when combined with voluntary exercises. This study aimed to investigate the safety and effects of the WB-NMES on hemodynamics, arrhythmia, and sublingual microcirculation. The study included 19 healthy Japanese volunteers, aged 22–33 years, who were not using any medication. Electrocardiogram (ECG), echocardiography, and blood sampling were conducted before a 20-min WB-NMES session and at 0 and 10 min after termination of WB-NMES. Their tolerable maximum intensity was recorded using numeric rating scale. Arrhythmia was not detected during neuromuscular electrical stimulation or during 10 min of recovery. Blood pressure, heart rate, left ventricular ejection fraction, and diastolic function remained unchanged; however, mild mitral regurgitation was transiently observed during WB-NMES in a single male participant. A decrease in blood glucose and an increase in blood lactate levels were observed, but no changes in blood fluidity, sublingual microcirculation, blood levels of noradrenaline, or oxidative stress were shown. WB-NMES is safe and effective for decreasing blood glucose and increasing blood lactate levels without changing the blood fluidity or microcirculation in healthy people.

Hemorheology of ischemic stroke (review)

Нарастающая распространенность ишемического инсульта (ИИ) ставит перед исследователями новые задачи в обеспечении прогнозирования и диагностики. Одной из альтернатив традиционным методам диагностики ИИ является гемореология. Это относительно недорогие методы в применении, не требующие дорогостоящих расходных материалов. В русскоязычной литературе методам гемореологии уделено мало внимания. В статье представлен подробный обзор публикаций по гемореологии ИИ. Освещены работы по характеристике реологических нарушений, встречающихся у пациентов с це- ребральной ишемией, с рентгенологическими признаками патологии церебральных сосудов. Приведены данные о показателях ухудшения текучести крови, включающие повышение вязкости плазмы, нарушение деформируемости и агрегации эритроцитов, которые наблюдается задолго до манифестации ИИ, а также являются факторами риска развития стойкого неврологического ухудшения во время госпитализации после острого ИИ и увеличения срока госпитализации. Очерчен круг клинических ситуаций ИИ, в которых реологические методы получили применение при оценке эффективности терапевтических стратегий (тромболизиса, гемодилюции, афереза, медикаментозной коррекции). The increasing prevalence of ischemic stroke (IS) poses new challenges for researchers in providing prognosis and diagnosis. Hemorheological methods is one of the alternatives to the traditional methods for IS diagnosis they are relatively inexpensive and do not require expensive consumables. In Russian-language literature little attention is paid to hemorheological methods. The article presents a detailed review about hemorheology in IS, characteristics of rheological disorders that occur in patients with cerebral ischemia, with radiological signs of cerebral vascular pathology. The data are presented about disturbances of blood fluidity, including increased plasma viscosity, impaired deformability and aggregation of red blood cells that are observed long before IS manifestation, and are the risk factors for persistent neurological aggravation during hospitalization after acute IS and increase the period of hospitalization. Clinical IS situations are described, in which rheological methods have been used for assessing the effectiveness of therapeutic strategies (thrombolysis, hemodilution, apheresis, drug correction).

Anti-tyrosinase and Anti-oxidative Activities by Asana: the Heartwood of Pterocarpusmarsupium

Asana (the heartwood of Pterocarpus marsupium) has been utilized as an agent for diabetes mellitus in Ayurveda traditional medicine. In our research program to explore novel functions of asana extract, we focused on its skin-whitening effect because asana has been used as a remedy for chronic skin diseases. In addition, the authors have already reported an improvement in blood fluidity that brightens dull facial skin. Based on these effects, asana is a promising candidate agent that possesses both blood fluidity and anti-tyrosinase activities. We focused on the anti-tyrosinase activity and anti-oxidative activities of asana and the results are summarized in this report. We found that a 50% ethanolic extract obtained from asana (PM-ext) showed 23%, 53%, and 71% inhibition against mushroom tyrosinase at 12.5, 50, and 200 µg/mL. Oxyresveratrol and isoliquiritigenin were identified as the active compounds by activity-guided purification. Oxyresveratrol has higher potency than isoliquiritigenin and the IC50 of oxyresveratrol was estimated to be 2.1 µM. On the other hand, isoliquiritigenin showed 21%, 28%, and 38% inhibition at 10, 50, and 100 µM, respectively. The inhibitory activity of oxyresveratrol was compared with 3 stilbenes, pterostilbene, resveratrol, and piceatannol. Although oxyresveratrol showed 72.8%, 81.0%, and 85.4% inhibition at 2, 5, and 10 µM, respectively, pterostilbene, resveratrol, and piceatannol showed no effects at the same concentration; these compounds also demonstrated anti-melanogenesis activity on B16 murine melanoma cells. As a result, oxyresveratrol showed the most potent activity, without cytotoxicity, with 38%, 74%, and 84% inhibition at 2, 10, and 20 µM, respectively, while pterostilbene showed 26%, 71%, and 79% inhibition at the same concentration with cytotoxicity at 10 and 20 µM. Resveratrol showed 20%, 41%, and 57% inhibition without cytotoxicity at 2, 10, and 20 µM, respectively. Auto-oxidation is one of the major factors in melanin biosynthesis and anti-oxidative activity is suitable for an anti-melanogenesis agent. We investigated the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity by PM-ext. As a result, PM-ext showed 16%, 33%, and 73% DPPH radical-scavenging activity at 10, 20, and 50 µg/mL, respectively. Oxyresveratrol showed 19%, 31%, and 59% scavenging activity at 10, 20, and 50 µM, respectively, similar to piceatannol. In addition, PM-ext showed 29%, 48%, and 80% suppressive activity on AGEs production at 3.1, 12.5, and 50 µg/mL, respectively. Oxyresveratrol showed 32%, 47%, and 55% activity at 10, 50, and 100 µM, respectively, and this was the most potent among the stilbenes tested. These results suggest that PM-ext could be a promising candidate as skin-whitening agent.