Uric acid and uric acid/creatinine ratio and their correlations with the hemorheological determinants in subjects with subclinical carotid atherosclerosis

BACKGROUND AND OBJECTIVE: we have examined the concentration of serum uric acid and the serum uric acid/creatinine ratio as well as their correlations with the main determinants of the hemorheological profile in a group of subjects with subclinical carotid atherosclerosis. METHODS: we evaluated the concentration of serum uric acid and the serum uric acid/creatine ratio in 43 men and 57 women [median age 66.00 (25)] with subclinical carotid atherosclerosis, subsequently divided according to the number of traditional cardiovascular risk factors and to the insulin resistance degree. RESULTS: serum uric acid, but not the serum uric acid/creatinine ratio, results strongly influenced by the number of cardiovascular risk factors and by the insulin resistance degree. In the whole group and in the subgroups of subclinical carotid atherosclerosis subjects, serum uric acid and serum uric acid/creatinine ratio show significant correlation, besides with whole blood viscosity, with plasma viscosity and erythrocyte aggregation. The influence of the serum uric acid on the erythrocyte aggregability that is a part of the erythrocyte aggregation is to ascribe to the action carried out by serum uric acid on the erythrocyte zeta potential. CONCLUSIONS: it is reasonable to think that the treatment of the asymptomatic or symptomatic hyperuricemia with the urate-lowering therapy that reduces the serum uric acid concentration may reflect on the hemorheological profile which role on the atherosclerotic cardiovascular disease is well known.

Epistaxis as a marker of the unfavorable course of hypertension

The aim of this research was to study changes in the nasal mucosa vessels in hypertensive patients suffering from recurrent epistaxis. Patients and methods. 78 hypertensive patients aged between 50 and 70, admitted due to epistaxis, were studied. Diabetic, coagulopathic patients and those taking anticoagulants were excluded from the research. All the patients were divided into 2 groups: group 1 (46 people) with a single epistaxis, group 2 (32 people) with a recurrent epistaxis. At the admission, all the patients showed elevated blood pressure, yet the differences between the patients of group 1 and group 2 were not significant. 14 patients of group 2 did not reveal any source of hemorrhage due to a severely deviated septum. These patients underwent septoplasty followed by mucoperichondrium biopsy. Histological study of the samples showed multiple erosions within the epithelial layer, as well as necrotic patches spreading to the deeper mucous coat layers. The microvasculature showed dystrophic changes in the endothelium, its focal desquamation with basal membrane exposure and thrombocytes and erythrocytes adhesion at such places, erythrocyte aggregation, plasma separation, erythrocyte and fibrinous thrombi formation. Thus, the cause of epistaxis is not high blood pressure, but those changes in the nasal mucosa vessels promoted by long-term arterial hypertension.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient’s age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

The chromatin-remodeling enzyme Smarca5 regulates erythrocyte aggregation via Keap1-Nrf2 signaling

Although thrombosis has been extensively studied using various animal models, our understanding of the underlying mechanism remains elusive. Here, using zebrafish model, we demonstrated that smarca5-deficient red blood cells (RBCs) formed blood clots in the caudal vein plexus. We further used the anti-thrombosis drugs to treat smarca5zko1049a embryos and found that a thrombin inhibitor, argatroban, partially prevented blood clot formation in smarca5zko1049a. To explore the regulatory mechanism of smarca5 in RBC homeostasis, we profiled the chromatin accessibility landscape and transcriptome features in RBCs from smarca5zko1049a and their siblings and found that both the chromatin accessibility at the keap1a promoter and expression of keap1a were decreased. Keap1 is a suppressor protein of Nrf2, which is a major regulator of oxidative responses. We further identified that the expression of hmox1a, a downstream target of Keap1-Nrf2 signaling pathway, was markedly increased upon smarca5 deletion. Importantly, overexpression of keap1a or knockdown of hmox1a partially rescued the blood clot formation, suggesting that the disrupted Keap1-Nrf2 signaling is responsible for the RBC aggregation in smarca5 mutants. Together, our study using zebrafish smarca5 mutants characterizes a novel role for smarca5 in RBC aggregation, which may provide a new venous thrombosis animal model to support drug screening and pre-clinical therapeutic assessments to treat thrombosis.

Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early-Onset Preeclampsia

We investigated peripartum maternal red blood cell (RBC) properties in early-onset preeclampsia (PE). Repeated blood samples were taken prospectively for hemorheological measurements at PE diagnosis (n = 13) or during 26–34 weeks of gestation in healthy pregnancies (n = 24), then at delivery, and 72 h postpartum. RBC aggregation was characterized by M index (infrared light transmission between the aggregated RBCs in stasis) and aggregation index (AI—laser backscattering from the RBC aggregates). We observed significantly elevated RBC aggregation (M index = 9.8 vs. 8.5; AI = 72.9% vs. 67.5%; p < 0.001) and reduced RBC deformability in PE (p < 0.05). A positive linear relationship was observed between AI and gestational age at birth in PE by regression analysis (R2 = 0.554; p = 0.006). ROC analysis of AI showed an AUC of 0.84 (0.68–0.99) (p = 0.001) for PE and indicated a cutoff of 69.4% (sensitivity = 83.3%; specificity = 62.5%), while M values showed an AUC of 0.75 (0.58–0.92) (p = 0.019) and indicated a cutoff of 8.39 (sensitivity = 90.9% and specificity = 50%). The predicted probabilities from the combination of AI and M variables showed increased AUC = 0.90 (0.79–1.00) (p < 0.001). Our results established impaired microcirculation in early-onset PE manifesting as deteriorated maternal RBC properties. The longer the pathologic pregnancy persists, the more pronounced the maternal erythrocyte aggregation. AI and M index could help in the prognostication of early-onset PE, but further investigations are warranted to confirm the prognostic role before the onset of symptoms.

Effects of preformed physical factors on blood rheology in patients with chronic post-embolic pulmonary hypertension

Введение. Основу взаимодействия физических факторов и организма составляют электрические и биоэнергетические процессы, вызывающие изменения показателей центральной и периферической гемодинамики, обменных процессов, трофики, дыхания, реактивности и сопротивляемости организма. К таким физическим факторам, в частности, относятся электромагнитные колебания оптического излучения или фототерапия. Цель исследования - оценка эффективности воздействия коротковолнового излучения (фотогемотерапии, ФГТ) и ультрафиолетового (УФ) облучения крови на ее реологические свойства в комплексной терапии больных хронической постэмболической легочной гипертензией (ХПЛГ). Методика. Проведено комплексное клинико-лабораторное обследование 64 пациентов (30 женщин и 34 мужчины), поступивших в клинику с симптомами хронической легочной недостаточности, развившейся после перенесенной тромбоэмболии легочной артерии. Больные ХПЛГ были распределены в 3 группы: 1-ю (контрольную) группу составили 15 пациентов, получавшие только базисное лечение; 2-ю (экспериментальную) группу - 26 больных, получавшие базисную терапию в комплексе с ФГТ; 3-ю (экспериментальную) группу - 23 пациента, которые получали базисную терапию в сочетании с воздействием на кровь УФ облучения. Для ФГТ синим светом и УФ воздействия на кровь применяли аппараты АФС-Соларис (Россия) со светодиодами, излучающими синий свет с длиной волны 450 ± 10 нм, и УФ лучи с длиной волны 365 ± 10 нм. Исследовали вязкость крови на ротационном вискозиметре RotoVisco-100 (Нааке GmbH, Германия) в диапазоне скоростей сдвига от 1 до 150 с-1, агрегацию эритроцитов на колориметре-нефелометре ФЭК-56 М (Россия), показатель гематокрита на гематокритной центрифуге (Autocrit, США). Результаты. У больных 1-й группы после базисного медикаментозного лечения отсутствовали статистически значимые изменения вязкости крови, агрегации эритроцитов и показателя гематокрита. У пациентов как 2-й, так и 3-й группы выявлены статистически значимые изменения реологических свойств крови: снижение вязкости крови, агрегации эритроцитов, показателя гематокрита. Заключение. Оптическое излучение синего света имеет выраженное физиологическое воздействие: вызывает медленный, но пролонгированный положительный эффект на реологические свойства крови. УФ облучение при воздействии на кровь также способствует улучшению гемореологии и циркуляции крови и активирует рудиментарные механизмы, запускающие адаптационные системы организма, ранее не функционирующие. Introduction. Electrical and bioenergetic processes that cause changes in central and peripheral hemodynamics, metabolic processes, trophism, respiration, reactivity, and body resistance are the basis of interaction between physical factors and the body. Such physical factors include, in particular, electromagnetic oscillations of the optical radiation or phototherapy. Aim: to assess the effectiveness of short-wave radiation (photohemotherapy, PHT) and ultraviolet (UV) irradiation of blood on its rheology in the complex treatment of chronic post-embolic pulmonary hypertension (CPPH). Methods. 64 patients (30 women and 34 men) with symptoms of chronic pulmonary insufficiency secondary to pulmonary embolism underwent a comprehensive clinical and laboratory examination. CPPH patients were divided into 3 groups: the 1st (control) group consisting of 15 patients who received only a basic treatment; the 2nd (experimental) group including 26 patients who received a basic therapy combined with PHT; and the 3rd (experimental) group consisting of 23 patients who received a basic therapy combined with UV irradiation of blood. AFS-Solaris devices (Russia) producing light-emitting diode-derived blue light with a wavelength of 450 ± 10 nm were used for FGT, and UV rays with a wavelength of 365 ± 10 nm were used for the UV exposure of blood. Blood viscosity was measured on a RotoVisco-100 (Нааке GmbH, Germany) rotational viscometer at shear rates ranging from 1 to 150 s-1; erythrocyte aggregation was studied with a FEK-56 M (Russia) colorimeter-nephelometer; and hematocrit was measured with a hematocrit centrifuge (Autocrit, USA). Results. There were no statistically significant changes in blood viscosity, erythrocyte aggregation, or hematocrit values in the 1st group after the basic treatment. Statistically significant changes in blood rheology parameters observed in both the 2nd and 3rd groups included decreases in blood viscosity, erythrocyte aggregation, and hematocrit values. Conclusion. Optical irradiation with blue light exerted a pronounced physiological effect evident as a slow but long-standing positive influence on blood rheology parameters. The UV irradiation of blood also improved hemorheology and blood circulation and activated rudimentary mechanisms triggering previously non-functional adaptive systems.

The role of hemorheological disorders in the pathogenesis of hemorrhagic pancreonecrosis

Введение. Вопросы патогенеза острого панкреатита и панкреонекроза до настоящего времени остаются в центре внимания исследователей и клиницистов. До сих пор до конца не выяснена роль изменений в системе гемостаза и гемореологических нарушений в развитии этого заболевания. Цель исследования: установить роль гемореологических нарушений в патогенезе геморрагического панкреонекроза и изучить специфику механизма этих расстройств. Материалы и методы. Обследовано 29 пациентов с геморрагическим панкреонекрозом (12 женщин и 17 мужчин) в возрасте от 23 до 60 лет. Исследовали вязкость крови, показатель гематокрита, количество эритроцитов и их диаметр, агрегацию, электрофоретическую подвижность, деформируемость и механическую резистентность эритроцитов, белковый состав плазмы, содержание сиаловой кислоты в плазме и в эритроцитах, параметры липидного обмена, содержание кальция и фибриногена в крови,фибринолитическую активность крови и агрегационную активность тромбоцитов, гемокоагуляционная активность исследована методом тромбоэластографии. Для определения нормальных значений исследованных показателей было обследовано 15 практически здоровых лиц (7 женщин и 8 мужчин). Результаты. У больных панкреонекрозом самым грубым нарушениям подвергаются эритроциты: их механическая резистентность снижалась в 2 раза, объем увеличивался на 18,7%, деформируемость падала на 43,8%, количество снижалось на 8,75%, показатель гематокрита при этом оставался на уровне нормальных значений по причине увеличенного объема (сферичности) клеток; в 1,8 раза возрастала агрегация эритроцитов. Вязкость крови при скорости сдвига 1 c–1 увеличивалась в 3,3 раза, а при скорости сдвига 150 c–1 — в 1,58 раза по сравнению с нормой. Причиной повышения агрегации эритроцитов являлось снижение их электрофоретической подвижности на 35,9% из-за десиализации их мембран: концентрация сиаловой кислоты в клеточных мембранах была снижена на 20,8%, а содержание конъюгированной сиаловой кислоты в плазме увеличено в 2,25 раза по сравнению с нормальными значениями. Заключение. Гемореологические расстройства, которые возникают первоначально у больных геморрагическим панкреонекрозом как результат некротических изменений поджелудочной железы, с определенного, довольно раннего этапа сами становятся фактором патогенеза данного заболевания. Доминирующим фактором прогрессивного увеличения вязкости крови у больных панкреонекрозом является нарушение морфофункциональных и физико-химических свой ств эритроцитов на фоне высокой активности протеолитических ферментов, биологически активных аминов и крайней степени токсемии. Background. The pathogenesis of acute pancreatitis and pancreonecrosis is still the focus of researchers and clinicians. The role of hemorheological disorders in these diseases remain uncertain until now. Objectives: to define the role of hemorheological disorders in the pathogenesis of hemorrhagic pancreonecrosis and to study the specifics of the mechanism of these disorders. Patients/Methods. This study included 29 patients (12 women and 17 men, age of 23 to 60 years old) with hemorrhagic pancreatic necrosis. We examined blood viscosity, hematocrit and some erythrocyte properties as count, diameter, aggregation, electrophoretic mobility, deformability and mechanical resistance; other investigated parameters were plasma protein composition, plasma and erythrocytes sialic acid concentrations, lipids, total calcium and fibrinogen concentrations, blood fibrinolytic activity, platelets aggregation activity; total hemocoagulation activity was studied with thromboelastography. Control group contained 15 practically healthy individuals (7 women and 8 men). Results. Expressed disturbances of blood rheological properties, mostly in erythrocytes were detected in patients with pancreonecrosis. Red blood cells (RBC) showed 2-times decreasing of mechanical resistance, of their volume by 18.7%, of deformability by 43.8%, of count by 8.75%. Hematocrit remained normal level due to RBC increased volume (sphericity). RBC aggregation had been increased by 1.8 times. Blood viscosity at the shear rate of 1 s–1 was increased by 3.3 times and at the shear rate of 150 s–1 by 1.58 times. Raised erythrocyte aggregation was caused by a decrease of RBC electrophoretic mobility of 35.9%. Sialic acid concentration in RBC membranes was lower of 20.8% whereas conjugated sialic acid in plasma showed increasing by 2.25 times. Conclusions. RBC morphofunctional and physicochemical disturbances cause the increase in blood viscosity in patients with pancreonecrosis. It is distinguishing feature of hemorheological disorders in hemorrhagic pancreonecrosis developing, seems, due to high activity of proteolytic enzymes and biologically active amines. Of particular importance in hemorrhagic pancreonecrosis belong to platelet involving into intravascular coagulation.

The chromatin-remodeling enzyme Smarca5 regulates erythrocyte aggregation via Keap1-Nrf2 signaling

Although thrombosis has been extensively studied using various animal models, however, our understanding of the underlying mechanism remains elusive. Here, using zebrafish model, we demonstrated that smarca5-deficient red blood cells (RBCs) formed blood clots in the caudal vein plexus that mimics venous thrombosis. We further used the anti-thrombosis drugs to treat smarca5zko1049a embryos and found that a thrombin inhibitor, argatroban, partially prevented blood clot formation in smarca5zko1049a. To explore the regulatory mechanism of smarca5 in RBC homeostasis, we profiled the chromatin accessibility landscape and transcriptome features in RBCs from smarca5zko1049a and their siblings and found that both the chromatin accessibility at the keap1a promoter and expression of keap1a were decreased. Keap1 is a suppressor protein of Nrf2, which is a major regulator of oxidative responses. We further identified that the expression of hmox1a, a downstream target of Keap1-Nrf2 signaling pathway, was markedly increased upon smarca5 deletion. Importantly, overexpression of keap1a or knockdown of hmox1a partially rescued the blood clot formation, suggesting that the disrupted Keap1-Nrf2 signaling is responsible for the venous thrombosis-like phenotypes in smarca5 mutants. Together, our study using zebrafish smarca5 mutants not only characterizes a novel role for smarca5 in blood clot formation, but also provides a new venous thrombosis animal model to support drug screening and pre-clinical therapeutic assessments to treat thrombosis.

Beneficial postoperative micro-rheological effects of intraoperative administration of diclophenac or ischemic preconditioning in patients with lower extremity operations –Preliminary data

BACKGROUND: Ischemia-reperfusion (I/R) may worsen blood rheology that has been demonstrated by clinical and experimental data. It is also known that anti-inflammatory agents and preconditioning methods may reduce I/R injury. OBJECTIVE: We aimed to analyze hemorheological alterations in elective knee operations and the effects of intraoperative nonsteroidal anti-inflammatory drug (NSAID) administration and application of ischemic preconditioning. METHODS: Hemorheological variables of 17 patients with total knee replacement or anterior crucial ligament replacement were analyzed. The ischemic (tourniquet) time was 92±15 minutes. Seven patients did not receive NSAID (Control group), 5 patients got i.v. sodium-diclophenac 10 minutes before and 6 hours after reperfusion. Five patients had ischemic preconditioning (3×15 minutes). Blood samples were collected before the ischemia, 10 minutes after reperfusion, on the 1st and 2nd p.o. day. RESULTS: Whole blood viscosity didn’t show notable inter-group differences, except for a slight decrease in the preconditioning group. RBC deformability decreased, erythrocyte aggregation enhanced by the 1st and 2nd p.o. days in Control group. In NSAID and preconditioning groups the changes were moderate, aggregation values significantly lowered compared to the Control group. CONCLUSION: Intraoperatively administered diclophenac or ischemic preconditioning could moderate the deterioration in micro-rheological parameters caused by I/R in patients.