Modulation Of Blood Flow Research Articles

Rab GTPases as Modulators of Vascular Function.

Rab GTPases, the largest family of small GTPases, are ubiquitously expressed proteins that control various aspects of cellular function, from cell survival to exocytosis. Rabs cycle between the GDP-bound inactive form and the GTP-bound active form. When activated, specific Rab GTPase-positive vesicles mediate cellular networks involved in intracellular trafficking, recycling, and/or exocytosis of cargo proteins. Dysfunctional Rab signaling pathways have been implicated in various disease processes. The precise cellular functions of several members of the Rab GTPase family are still unknown. A lack of pharmacological tools and the lethality of gene knockouts have made more detailed characterizations of their protein interaction networks difficult. Nevertheless, available evidence suggests that these proteins are vital for normal cell function. Endothelial and smooth muscle cells control vascular lumen diameter and modulate blood flow. Endothelial cells also secrete several pro- and antithrombotic factors and vasoactive substances to coordinate local inflammatory responses and angiogenesis. Rab GTPase function in endothelial cells has been relatively well-explored, while only a handful of reports are available on these proteins in vascular smooth muscle. This review summarizes the present knowledge on Rab GTPases in the vasculature.

Imposed positive defocus changes choroidal blood flow in young human subjects

PurposeIt has previously been found that imposing positive defocus changes axial length and choroidal thickness after only 30 min. In the present study, we investigated whether these changes may result from an altered choroidal blood flow.MethodsEighteen young adult subjects watched a movie from a large screen (65 in.) in a dark room at 2 m distance. A 15-min wash-out period was followed by 30 min of watching the movie with a monocular positive defocus (+ 2.5D). Changes in axial length and ocular blood flow were measured before and after the defocus, by using low-coherent interferometer (LS 900, Haag-Streit, Switzerland) and a laser speckle flowgraphy (LSFG) RetFlow unit (Nidek Co., LTD, Japan), respectively. Three regions were analyzed: (1) the macular area, where choroidal blood flow can be measured, (2) the optic nerve head (ONH), and (3) retinal vessel segments.ResultsChanges in choroidal blood flow were significantly and negatively correlated with changes in axial length that followed positive defocus in exposed eyes (R = − 0.67, p < 0.01). The absolute values of changes in choroidal blood flow in the defocused eyes were significantly larger than in the fellow control eyes (2.35 ± 2.16 AU vs. 1.37 ± 1.44 AU, respectively, p < 0.05). ONH and retinal blood flow were not associated with the induced changes in axial length.ConclusionsPositive defocus selectively alters choroidal, but not retinal or ONH blood flow in young human subjects after short-term visual exposure. The results suggest that blood flow modulation is involved in the mechanism of choroidal responses to optical defocus.

Differences in the limb blood flow between two types of blood flow restriction cuffs: A pilot study.

Introduction: The determination of the optimal occlusion level is a key parameter in blood flow restriction (BFR). This study aimed to compare the effects of elastic (BStrong) vs. nylon (Hokanson) BFR cuffs on blood flow in the lower and upper limbs. Methods: Eleven healthy participants undertook several BFR sessions with 2 different cuffs of similar width on their lower and upper limbs at different pressures [200, 250, 300, 350, and 400 mmHg for BStrong and 0, 40, and 60% of the arterial occlusion pressure (AOP) for Hokanson]. Doppler ultrasound recorded blood flows through the brachial and femoral artery at rest. Results: With BStrong, only 350 and 400 mmHg pressures were significantly different from resting values (0% AOP). With Hokanson, both 40% and 60% of the AOP were significantly different from resting values (p < 0.05). Discussion: While both cuffs elicited BFR, they failed to accurately modulate blood flow. Hokanson is appropriate for research settings while BStrong appears to be a convenient tool for practitioners due to its safety (i.e., the impossibility of completely occluding arteries) and the possibility of exercising freely detached from the pump.

Computational Analysis of Flow Structures in Turbulent Ventricular Blood Flow Associated With Mitral Valve Intervention.

Cardiac disease and clinical intervention may both lead to an increased risk for thrombosis events due to a modified blood flow in the heart, and thereby a change in the mechanical stimuli of blood cells passing through the chambers of the heart. Specifically, the degree of platelet activation is influenced by the level and type of mechanical stresses in the blood flow. In this article we analyze the blood flow in the left ventricle of the heart through a computational model constructed from patient-specific data. The blood flow in the ventricle is modelled by the Navier-Stokes equations, and the flow through the mitral valve by a parameterized model which represents the projected opening of the valve. A finite element method is used to solve the equations, from which a simulation of the velocity and pressure of the blood flow is constructed. The intraventricular blood flow is complex, in particular in diastole when the inflow jet from the atrium breaks down into turbulent flow on a range of scales. A triple decomposition of the velocity gradient tensor is then used to distinguish between rigid body rotational flow, irrotational straining flow, and shear flow. The triple decomposition enables the separation of three fundamentally different flow structures, that each generates a distinct type of mechanical stimulus on the blood cells in the flow. We compare the results in a simulation where a mitral valve clip intervention is modelled, which leads to a significant modification of the intraventricular flow. Further, we perform a sensitivity study of the results with respect to the positioning of the clip. It was found that the shear in the simulation cases treated with clips increased more compared to the untreated case than the rotation and strain did. A decrease in valve opening area of 64% in one of the cases led to a 90% increase in rotation and strain, but a 150% increase in shear. The computational analysis opens up for improvements in models of shear-induced platelet activation, by offering an algorithm to distinguish shear from other modalities in intraventricular blood flow.

A dorsalis pedis venous flap containing a U-shaped venous arch for the reconstruction of fingertip defects.

In small-area soft tissue defects of the fingers, venous flaps have the advantages of easy design and harvesting, and also a thin and flexible texture. Although the artery-vein-vein (A-V-V) pattern is the safest pattern, the tiny veins in the finger pulp make anastomosis difficult. We have designed a modified blood flow pattern flap using the dorsum of the foot as the donor site and anastomosing the U-shaped blood vessels in the venous flap with the two digital arteries in an artery-vein-artery (A-V-A) pattern to reconstruct the digital arterial arch without the need for venous anastomosis. Our study included 22 patients with 23 fingertip defects. In the 23 fingers, 18 flaps survived completely and four had only partial marginal necrosis. The donor site healed well without significant scar hyperplasia.Level of evidence: IV.

CD44 mediates shear stress mechanotransduction in an in vitro blood-brain barrier model through small GTPases RhoA and Rac1.

Fluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the effect of shear on the blood-brain barrier (BBB) have yet to be clarified in cerebral vasculature despite its importance for brain homeostasis. The goal of this study is to probe components of shear mechanotransduction within the BBB to gain a better understanding of pathologies associated with changes in cerebral perfusion including ischemic stroke. Interrogating the effects of shear stress in vivo is complicated by the complexity of factors in the brain parenchyma and the difficulty associated with modulating blood flow regimes. The in vitro model used in this study is compatible with real-time measurement of barrier function using a transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level of shear stress required for barrier formation and that the composition of the extracellular matrix, specifically the presence of high molecular weight hyaluronan, dictates the flow response. Gene editing to modulate the expression of CD44, a mechanosensitive receptor for hyaluronan, demonstrates that the receptor is required for the endothelial response to shear stress. Manipulation of small GTPase activity reveals CD44 activates Rac1 while inhibiting RhoA activation. Additionally, adducin-γ localizes to tight junctions in response to shear stress and RhoA inhibition and is required to maintain the barrier. This study identifies specific components of the mechanosensing complex associated with the BBB response to fluid shear stress and, therefore, illuminates potential targets for barrier manipulation in vivo.

Skin Micrograph Protector in a Burn Wound: Alloderm or Hydrogel Coating?

AIM OF STUDY Was to compare the dynamics of engraftment of skin micrographs in a burn wound when using protectors from an allodermal graft and from a hydrogel coating.MATERIAL AND METHODS The experimental study was conducted on 18 rats with a scab formed 3 days after modeling a deep burn with an area of 20% of the body surface. Partial fascial necrectomy was performed: two rounded sections of the sling with a diameter of 25 mm were excised. 6 automicrographs of skin 4x4 mm, 0.3 mm thick, were applied to each surface freed from the scab. In each animal, micrographs on one of the wounds were covered with a hydrogel protector, on the other with an allodermotransplant from another animal of the group. A secondary aseptic dressing was applied to the protectors. On the 5th and 20th days after the operation, the state of micrographs was studied: blood circulation — according to laser Doppler flowmetry, microstructure in vivo — using optical coherence tomography, microstructure ex vivo — according to histological examination of biopsies.ReSUlTS Differences in the rate of restoration of blood circulation of micrographs in the early stages of the postoperative period were found. In the first 5 days, the perfusion of micrographs under an allodermal protector exceeded the indicator in micrographs under a hydrogel coating by 44 [21; 51] % (p=0.031) due to the contribution of endothelial and neurogenic mechanisms of blood flow modulation. Starting from day 10, the differences in perfusion were levelled, but there were signs of more active endothelial regulation of blood flow under the skin (p=0.028). Histologically, the appearance of full-blooded capillaries was revealed earlier in micrographs under the alloderm than when using a hydrogel protector. By 20 days, under the condition of regular change of hydrogel coatings, the area of wound healing under the studied coatings did not significantly differ. However, the structure of the integumentary tissue under the alloderm according to the optical coherence tomography data was closer to normal skin than when using a hydrogel protector.CONClUSIONS From the point of view of the physiology of the wound process, alloderm is the preferred option of an autograft protector in comparison with a hydrogel coating, which is probably due to the paracrine biological activity of the alloderm. However, hydrogel coatings can provide a comparable level of efficiency, provided they are regularly changed and, potentially, given the properties of cytokine activity.

Vascular Injury in the Zebrafish Tail Modulates Blood Flow and Peak Wall Shear Stress to Restore Embryonic Circular Network.

Mechano-responsive signaling pathways enable blood vessels within a connected network to structurally adapt to partition of blood flow between organ systems. Wall shear stress (WSS) modulates endothelial cell proliferation and arteriovenous specification. Here, we study vascular regeneration in a zebrafish model by using tail amputation to disrupt the embryonic circulatory loop (ECL) at 3 days post fertilization (dpf). We observed a local increase in blood flow and peak WSS in the Segmental Artery (SeA) immediately adjacent to the amputation site. By manipulating blood flow and WSS via changes in blood viscosity and myocardial contractility, we show that the angiogenic Notch-ephrinb2 cascade is hemodynamically activated in the SeA to guide arteriogenesis and network reconnection. Taken together, ECL amputation induces changes in microvascular topology to partition blood flow and increase WSS-mediated Notch-ephrinb2 pathway, promoting new vascular arterial loop formation and restoring microcirculation.

Experimental testing of tannic acid target delivery system for correcting periodontal microcirculation

Objective: to study the effect of the targeted delivery system of tannic acid (TA) in silver alginate microcapsules on the state of gum microvasculature in rats with intact periodontium vs. experimental periodontitis. Materials and Methods. The study was conducted on 90 white rats, distributed among six groups: the control group, two groups with intact periodontium and single application of gel with microcapsules loaded/not loaded with TA, experimental periodontitis group, and two groups of animals with periodontitis and repeated application of gel with microcapsules loaded/not loaded with TA. We assessed gingival perfusion and blood flow modulation mechanisms in rats via laser Doppler flowmetry. Results. Applying gel with silver microcapsules to an intact gum in rats caused 7.5% transient increase in perfusion and activation of microcirculation modulation. Loading microcapsules with TA reduced the severity of transient microcirculatory changes. Using gel with TA-loaded capsules in rats with periodontitis allowed achieving a more pronounced normalization of perfusion and mechanisms of microcirculation modulation vs. using gel containing microcapsules without active components. Conclusion. Loading alginate microcapsules with silver ions and TA yielded reduction of the irritating effect on gingival mucosa accompanied by an increase in the effectiveness of correcting microcirculatory disorders in periodontitis.

FEATURES OF SKIN MICROCIRCULATION IN RATS OF DIFFERENT SEX AND AGE

Purpose. Investigate the parameters of skin microcirculation of rats of different sex and age by laser Doppler flowmetry.&#x0D; Materials and methods. The study was conducted on 60 mongrel rats of both sexes weighing 120-270 g. The first group included 20 rats aged 1 month, the second – 20 rats aged 6-12 months and the third – 20 rats aged more than 18-24 months. Microcirculation was studied using a laser Doppler flowmeter with zoletil-xylazine anesthesia on the skin of the anterior abdominal wall. Statistical analysis was performed using the application package Statistica 13.0 (StatSoft, USA).&#x0D; Results. The microcirculation index was slightly higher in males than in females rats in the skin of the animals’ abdomen. In the 1st age group, this difference was 8.96% (R=-0.27), in the 2nd - 4.19% (R=0.09), in the 3rd – 0.62% (R=-0.13). The myogenic tone index was consistently lower in males than in females – by 59.73% in 1st (R=0.12), by 9.86% in 2nd (R=0.20) and by 8.84% (R=0.46) in the 3rd age group. The microcirculation index was decreased by 11.15% (R=0.75) between 1st and 2nd age groups, by 39.04% (R=0.29) between 1st and 3rd age groups. The index ϭ (variable component of the microcirculation index) was increased in animals of the 2nd and 3rd groups. It indicated the preservation of the mechanisms of modulation of cutaneous blood flow in aged animals.&#x0D; Conclusion. There was no statistically significant dependence of the microcirculation index in the skin of the abdomen on the sex of the animals. The basic parameters of microcirculation and the amplitude-frequency spectrum were decreased in aged animals.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases.

Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects.

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient’s growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design criteria for shunt diameter changes. Then, two stages of prototyping were performed to design, build and test responsive hydrogel systems that facilitate tuning of the shunt diameter by adjusting the hydrogel’s degree of crosslinking. We examined two mechanisms to drive crosslinking: infusion of chemical crosslinking agents and near-UV photoinitiation. The growth model showed that 15–18% increases in shunt diameter were required to accommodate growing patients’ increasing blood flow; similarly, the computational models demonstrated that blood flow magnitudes were in agreement with previous reports. These target levels of diameter increases were achieved experimentally with model hydrogel systems. We also verified that the photocrosslinkable hydrogel, composed of methacrylated dextran, was contact-nonhemolytic. These results demonstrate proof-of-concept feasibility and reflect the first steps in the development of this novel blood shunt. A tunable shunt design offers a new methodology to rebalance blood flow in this vulnerable patient population during growth and development.

Study of the relationship between regional cerebral saturation and pCO2 changes during mechanical ventilation to evaluate modifications in cerebral perfusion in a newborn piglet model.

Near-infrared spectroscopy (NIRS) could be a useful continuous, non-invasive technique for monitoring the effect of partial pressure of carbon dioxide (PaCO2) fluctuations in the cerebral circulation during ventilation. The aim of this study was to examine the efficacy of NIRS to detect acute changes in cerebral blood flow following PaCO2 fluctuations after confirming the autoregulation physiology in piglets. Fourteen piglets (<72 h of life) were studied. Mean arterial blood pressure, oxygen saturation, pH, glycemia, hemoglobin, electrolytes, and temperature were monitored. Eight animals were used to evaluate brain autoregulation, assessing superior cava vein Doppler as a proxy of cerebral blood flow changing mean arterial blood pressure. Another 6 animals were used to assess hypercapnia generated by decreasing ventilatory settings and complementary CO2 through the ventilator circuit and hypocapnia due to increasing ventilatory settings. Cerebral blood flow was determined by jugular vein blood flow by Doppler and continuously monitored with NIRS. A decrease in PaCO2 was observed after hyperventilation (47.6±2.4 to 29.0±4.9 mmHg). An increase in PaCO2 was observed after hypoventilation (48.5±5.5 to 90.4±25.1 mmHg). A decrease in cerebral blood flow after hyperventilation (21.8±10.4 to 15.1±11.0 mL/min) and an increase after hypoventilation (23.4±8.4 to 38.3±10.5 mL/min) were detected by Doppler ultrasound. A significant correlation was found between cerebral oxygenation and Doppler-derived parameters of blood flow and PaCO2. Although cerebral NIRS monitoring is mainly used to detect changes in regional brain oxygenation, modifications in cerebral blood flow following experimental PaCO2 changes were detected in newborn piglets when no other important variables were modified.

Neurovascular disease: 2022 update.

In this update we present a series of papers focused on topics that have emerged in vascular disease over the prior year. The first two papers focus on the pathogenesis of vascular malformations, the first on brain arteriovenous malformations, and the second on cerebral cavernous malformations. These disorders can lead to significant brain injuries from intracerebral hemorrhage (if they rupture) or other neurological complications, including seizures. The next set of papers reflects work that has advanced our understanding of how the brain and the immune system "communicate" after brain injury, including stroke (papers 3-6). The first of these shows that T cells are involved in white matter repair after ischemic injury, an effect dependent on microglia, demonstrating the important cross-talk between innate and adaptive immunity. The next two papers focus on B cells, which have been relatively understudied in the context of brain injury. The contribution of antigen-experienced B cells from the meninges and skull bone marrow, rather than blood-derived B cells in neuroinflammation opens up a very novel area of investigation. The possibility that antibody secreting B cells may contribute to vascular dementia will certainly be an active area for future investigations. Similarly, in paper 6, investigators found that CNS-infiltrating myeloid cells can originate from brain borders tissues. These cells have unique transcriptional signatures that are distinct from their blood-derived counterparts, and likely contribute to myeloid cell infiltration from bone-marrow niches in close proximity to the brain. The contribution of microglia, the primary innate immune cell of the brain, to amyloid deposition and propagation is then discussed, followed by work on how perivascular Aβ is potentially cleared along the cerebral vessels in patients with cerebral amyloid angiopathy. The final two papers focus on the contribution of senescent endothelial cells and pericytes. The first used a model of accelerated senescence (Hutchinson-Gilford progeria syndrome; HGPS) and shows the translational potential of an approach to reduce telomere shortening to slow aging. The final paper demonstrates how capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain. Interestingly, several of the papers identified therapeutic strategies that could be potentially translated into clinical populations.

Drag-Reducing Polymers Improve Vascular Hemodynamics and Tissue Oxygen Supply in Mouse Model of Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia and glucose intolerance caused by impaired insulin action and/or defective insulin secretion. Long-term hyperglycaemia leads to various structural and functional microvascular changes within multiple tissues, including the brain, which involves blood-brain barrier alteration, inflammation and neuronal dysfunction. We have shown previously that drag-reducing polymers (DRP) improve microcirculation and tissue oxygen supply, thereby reducing neurologic impairment in different rat models of brain injury. We hypothesised that DRP could improve cerebral and skin microcirculation in the situation of progressive microangiopathies associated with diabetes using a mouse model of diabetes mellitus. Diabetes was induced in C57BL/6 J mice with five daily consecutive intraperitoneal injections of streptozotocin (50mg/kg/day). Animals with plasma glucose concentrations greater than 250mg/dL were considered diabetic and were used in the study following four months of diabetes. DRP (2ppm) was injected biweekly during the last two weeks of the experiment. Cortical and skin (ear) microvascular cerebral blood flow (mCBF) and tissue oxygen supply (NADH) were measured by two-photon laser scanning microscopy (2PLSM). Cerebrovascular reactivity (CVR) was evaluated by measuring changes in arteriolar diameters and NADH (tissue oxygen supply) during the hypercapnia test. Transient hypercapnia was induced by a 60-second increase of CO2 concentration in the inhalation mixture from 0% to 10%. Compared to non-diabetic animals, diabetic mice had a significant reduction in the density of functioning capillaries per mm3 (787±52 vs. 449±25), the linear velocity of blood flow (1.2±0.31 vs. 0.54±0.21mm/sec), and the tissue oxygen supply (p<0.05) in both brain and skin. DRP treatment was associated with a 50% increase in all three parameters (p<0.05). According to the hypercapnia test, CVR was impaired in both diabetic groups but more preserved in DRP mice (p<0.05). Our study in a diabetic mouse model has demonstrated the efficacy of hemorheological modulation of blood flow by DRP to achieve increased microcirculatory flows and tissue oxygen supply.

Preliminary Results of Hepatic Blood Flow Modulation in an Experimental Model of Hepatectomy – Implications for Hepatic Artery Buffer Response Modulation

Introduction: Portal hyperperfusion of the remnant liver has been implicated in post hepatectomy liver failure (PHLF) following major hepatectomy by inducing arterial vasoconstriction, also called Hepatic Artery Buffer Response (HABR). We aimed to compare the effect of a selective A2Aadenosine receptor agonist Regadenoson to a porto-caval (P-C) shunt in an experimental model of hepatectomy in piglets on hepatic blood flow modulation. Methods: A cohort study with cross-over design of serial doppler measurements in landrace pigs weighing 25-30 Kg was performed; all subjects underwent laparotomy and baseline measurements were taken. Thereafter extended left hepatectomy with P-C shunt was performed and measurements were repeated. Finally, the P-C shunt was occluded and all animals were administered intra-arterially 400mcg of regadenoson, prior repeating measurements. Results: The baseline portal vein and hepatic artery flow were 28.5 ± 7.47 ml/sec and 118.66 ± 19.28 ml/sec respectively. After hepatectomy a significant increase of the portal vein flow by 91.8% while the hepatic artery flow increase only by 26.4%, signifying activation of the HABR. Opening of the P-C shunt decreased the portal vein flow by 24.69% and a more pronounced decrease of hepatic artery flow (34.22%). After occlusion of the portocaval shunt and administration of regadenoson there was a minor decrease of the portal flow by 13.71% while there was a significant drop of the hepatic artery flow by 55.33%, thus more effectively decreasing arterial vasoconstriction (p<0.005). Conclusion: Regadenoson can more effectively decrease hepatic artery flow than PC shunt, thus signifying a potential role in the management of PHLF.

ПЕРФУЗІЙНА ДИСФУНКЦІЯ ПРИ ГОСТРОМУ ПАНКРЕАТИТІ: ПЕРСПЕКТИВНІ НАПРЯМКИ УДОСКОНАЛЕННЯ ДІАГНОСТИКИ ТА СТРАТИФІКАЦІЇ ЗАХВОРЮВАННЯ

Introduction. Acute pancreatitis (AP) is one of the most common diseases of the digestive system that require hospitalization. To date, the problem of stratification and differential diagnosis of AP in the early stages remains unresolved, which encourages the search for new methods of diagnosis and prediction of the severity of AP. Aim. To evaluate the possibility of creating a clinically oriented system of stratification and prognosis of AP on the basis of dynamic changes in microcirculation depending on the duration of the disease and severity of AP. Materials and methods. Assessment of the state of microcirculation (MC) of patients by laser Doppler flowmetry (LDF) was performed with the “LAKK-02” device. Kruskal-Wallis non-parametric analysis of variance and the median test were used to test statistical hypotheses when comparing independent samples. Pairwise comparison of independent samples was performed using the Mann-Whitney U test. Results. The study determined the indicators of MC in patients with different AP severity degrees on the first day of the disease. The microcirculation parameter (MP) in patients with mild, moderate, and severe AP was 3.9; 3.8 and 6.8 perfusion units (p.u.), respectively. The blood flow modulation rate (ơ) was 0.52; 0.54 and 0.69 p.u. in mild, moderate, and severe AP. In our study, the coefficient of variation (Kv) averaged 17.3%; 20.0% and 11.7% in patients with mild, moderate, and severe AP, respectively. Conclusions. LDF in AP is an informative method of diagnosing the state of MC, which is a universal link in all pathophysiological reactions of the organism. Changes of MC in AP depend on the severity of AP and the period of the disease. The pathophysiological microcirculatory phenomena, revealed on the first day of the disease, provide us with the perspectives of early clinical distinguishing the moderate and severe forms of AP from the so-called group of “destructive forms”.

Auxiliary Liver Transplantation for Cirrhosis: From APOLT to RAPID: A Scoping Review.

To survey the available literature regarding the use of auxiliary liver transplantation (ALT) in the setting of cirrhosis. ALT is a type of liver transplantation (LT) procedure in which part of the cirrhotic liver is resected and part of the liver graft is transplanted. The cirrhotic liver left in situ acts as an auxiliary liver until the graft has reached sufficient volume. Recently, a 2-stage concept named RAPID (Resection and Partial Liver segment 2/3 transplantation with Delayed total hepatectomy) was developed, which combines hypertrophy of the small graft followed by delayed removal of the native liver. A scoping review of the literature on ALT for cirrhosis was performed, focusing on the historical background of RAPID and the status of RAPID for this indication. The new comprehensive nomenclature for hepatectomy ("New World" terminology) was used in this review. A total of 72 cirrhotic patients underwent ALT [heterotopic (n = 34), orthotopic (Auxiliary partial orthotopic liver transplantation, n = 34 including 5 followed by resection of the native liver at the second stage) and RAPID (n = 4)]. Among the 9 2-stage LTs (APOLT, n = 5; RAPID, n = 4), portal blood flow modulation was performed in 6 patients by deportalization of the native liver (n = 4), portosystemic shunt creation (n = 1), splenic artery ligation (n = 3) or splenectomy (n = 1). The delay between the first and second stages ranged from 18 to 90 days. This procedure led to an increase in the graft-to-recipient weight ratio between 33% and 156%. Eight patients were alive at the last follow-up. Two-stage LT and, more recently, the RAPID procedure are viable options for increasing the number of transplantations for cirrhotic patients by using small grafts.

The root of the matter: nitrate-rich beetroot juice reduces skeletal muscle O2 uptake during exercise.

The root of the matter: nitrate-rich beetroot juice reduces skeletal muscle O2 uptake during exercise.

Impact of Adaptogens of Animal Origin on Microcirculation in Rats

Velvet antler products are adaptogens of animal origin, capable of increasing the physical and mental capacity of the body. It is known that the velvet antler products based the maral blood and a histolysate obtained from the genitals of males exhibit a more pronounced revitalizing effect. Experiments were conducted on 40 mature white male Wistar rats weighing 230±20 g, divided into 3 groups: intact group (n=20); control group (n=10); experimental group (n=10). The experimental group received a concentrate Pantohematogen (Lubyan’gem) at a dose of 2 ml per 100 g of body weight for 30 days; the control group – an aqueous solution of concentrate additives; the intact animals – water in the same volume. On the 31st day of the experiment, the microcirculation indicators of all animals were studied by laser doppler flowmetry. In comparison with intact animals, the rats of the experimental group receiving the concentrate for 30 days showed an increase in the blood flow modulation by 108% (p=0.006), in the amplitude of endothelial fluctuations by 71% (p=0.006), and in the amplitude of vasomotor waves by 45% (p=0.024). This indicates an intensification of the “active” mechanisms of microcirculation regulation.