Changes in the microcirculation of the oral mucosa in post-COVID-19 patients not receiving anti-coagulant therapy

Introduction. The outbreak of a new coronavirus infection has become a challenge for the global health system. The COVID-19 infection is directly related to various disorders of the cardiovascular system, including the microcirculatory bed, caused by thrombotic events and deteriorations of blood rheology. Aims. The paper reports on the results of a study of Doppler sonographic parameters changes in patients with a novel coronavirus infection over the past 6 months. Materials and methods. We assessed the oral mucosa microcirculation in three segments using the high-frequency ultrasound dopple-rography. Results. We recorded the linear and volumetric blood flow rates and the Gosling and Purselo indexes in the course of our work. When comparing the obtained average statistical parameters of blood flow velocity, the linear and volumetric blood flow rates in patients of both groups were found to be lain in the same range and the mean values of Vas, Vam, Qas were equal. The mean values of the Purselo resistance index were closer to 1,0 in patients with COVID-19, and the values of the Gosling pulsation index (PI) were on average 53.3 % higher than in the control group. Conclusion. We evaluated the screening capabilities and potential of high-frequency ultrasound dopplerography for use in patients of different age groups and different somatic status.

Correlation and spectral analysis of microcirculatory changes in symmetric areas of human head in short-term hypoxic exposure

Purpose. To study the effect of short-term hypoxic exposure on correlation between microcirculatory parameters (MCR) of symmetric areas of the human head. Materials and methods. MCR parameters of 10 healthy male volunteer were measured by laser Doppler flowmetry method. Short-term hypoxic exposure was produced according to the hypoxic test method using the ReOxy Cardio unit (S. A. Aimediq). We assessed the perfusion metrics left and right areas of interest, neurogenic, myogenic, respiratory and cardiac contributors to vascular tone and correlations between baseline parameters and after hypoxic exposure. Results. We revealed the specificity of regional circulation system rearranging induced by hypoxic load. The specificity is caused by functional asymmetry of correlations between different vascular tone contributors in symmetrical head areas. Strong correlation declining under the hypoxic loads between baseline perfusion on left/right was found. The perfusion changes of symmetrical temporal areas under the hypoxic loads correlate negatively with the baseline perfusion of both the same and the opposite side. Conclusion. Short-term hypoxic load rearranges the balance of different vascular tone contributors regulatory role in MCR of symmetric head areas to maintain the sustainable activity of the whole MRC.

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A microcirculation study to assess the effectiveness of post-COVID rehabilitation treatment

The objective of the research is to study distal circulation and assess the results of post-COVID rehabilitation treatment. A total of 107 reconvalescents were examined, with a control group of 56 patients. The effectiveness of therapy was estimated with the help of microcirculation parameters registered by the Minimax-Doppler-K system before and after the treatment. The authors found correlation between microcirculation measurements and data of objective examinations, as well as other procedures (electrocardiography, echocardiography, pulse oximetry) and the subjective examination of patient’s condition.

Comparative analysis of hemostasis system state indicators in severe COVID-19

Introduction. Clinical experience in managing patients with a new coronavirus infection caused by the SARS-CoV-2 allowed to identify specific hemostasis disorders, and enables to introduce the concept of COVID-associated coagulopathy. The aim of the study was to assess the direction of coagulogram parameter changes, whole blood clotting parameters and characteristics of platelet and plasma hemostasis in patients with severe COVID-19. Materials and methods. The parameters of the hemostasis system were assessed using venous blood of 12 patients with severe COVID-19 and 16 healthy volunteers. The whole blood clotting process was investigated by low-frequency piezothromboelastography. The platelet count and indicators of spontaneous and ADP-induced platelet aggregation were estimated with the help of a laser platelet aggregation analyzer. Fibrinolytic activity of plasma, plasminogen activity, content of fibrinogen, D-dimer, PTT, APTT, PTI and INR were assessed. Results. An increased level of fibrinogen, a 6-fold increased D-dimer level, and increased PTT were found in patients with severe COVID-19. The patient platelets count was reduced by 51 % (p <0.05), spontaneous platelet aggregation remained at nearly normal level. Almost complete inhibition of ADP-induced platelet reactivity and inhibition of XIIa-dependent fibrinolysis was revealed, despite an increased by 19.3 % (p <0.05) plasminogen activity. Parameters of the whole blood coagulation process pointed a pronounced activation of platelet hemostasis, a significant intensification of the polymerization stage of clot formation and an increased intensity of clot lysis and retraction. Conclusion. The significant increase of D-dimer level and paradoxical inhibition of plasma fibrinolytic activity revealed by test of XIIa-dependent fibrinolysis (in contrast to the increased intensity of clot lysis when assessing the coagulation of whole blood) indicate the complex pathogenic mechanisms of coagulopathy caused by SARS-CoV-2 infection, and the involvement of blood cells and the vascular wall in the process of pathological thrombus formation.

The potential of high-frequency ultrasound Dopplerography in the assessment of microcirculatory disorders in post-COVID-19 patients with a cardiovascular profile

Introduction. Patients with cardiovascular diseases have endothelial dysfunction and a higher risk of severe course of COVID-19, and thrombotic complications. Associated endotheliitis caused by virus penetration and cytokines storm leads to the release of tissue factor, the formation of excess thrombin and fibrin and thrombosis. The aim. To identify the potential of high-frequency ultrasound Dopplerography (HFUDG) for the assessment of microcirculatory disorders in post-COVID-19 patients with cardiovascular profile and to assess the microcirculatory bed condition before and after treatment with sulodexide. Materials and methods. 49 patients recovered from moderate-severe COVID-19 one month ago, aged 20–80, were examined. 24 patients, received prophylaxis with POACs for 1 month, formed group I, group II – 25 patients without prophylaxis. The nail bed of the upper limb 1st finger was examined using HFUDG and a 25 MHz sensor. Shape and spectrum of curves taken from dopplerograms were analyzed. The control examination was performed 4 weeks after therapy. Results. In patients after COVID19, depletion of spectral characteristics was revealed in comparison with dopplerograms of healthy individuals. The predominantly red part of the spectrum corresponding to the fastest particles was recorded. Slow-moving particles corresponding to the lighter part of the spectrum were nearly non-existent. In patients administrated POAC prophylaxis, amplitude indices were higher. Significant increase in D-dimer, antithrombin III, and soluble fibrin monomer complexes (SFMC) was also detected. The remaining parameters of the coagulogram were within the norm before and after treatment. After a course of sulodexide therapy, the spectral characteristics and coagulogram parameters returned to normal. Conclusion. HFUDG allows to detect stasis of capillary blood flow, the appearance of shunt blood flow corresponding to microtrombosis. Microcirculation indicators in post-COVID-19 patients improved after a course of preventive therapy with sulodexide.

Non-respiratory functions of lungs in experimental intracerebral hemorage during fingolimod injection

Introduction. Intracerebral hemorrhage (ICH) is frequently accompanied by respiratory system complications. One of the correction method of post stroke complications is administration of immunosuppressive drug fingolimod. Theobjective of the study is to investigate non-respiratory lung functions in experimental ICH during fingolimod treatment. Materials and methods. Animals were divided into 3 groups: group 1 with ICH, group 2 with ICH receiving fingolimod and group 3 as reference group. Intracranial hemorrhage was modelled by 160 μl autologic blood injection into lateral brain ventricle (P=0.6; D=1.5; V=3.5). Fingolimod (FTY 720, «Sigma») was administered within 1 hour after ICH (intraabdominal, 1 mg/kg). Biochemistry and functional parameters of the lung surfactant in animals were studied. Phospholipids fractions spectrum was assessed by thin-layer chromatography, superficial surfactant activity by Wilhelmi method. Parameters of water metabolism, pulmonary blood filling were studied by gravimetric method. Level of blood nitric oxide was estimated by amount of nitrates and nitrites stable terminal metabolites. Results. We revealed that experimental ICH causes a decrease of alveolar stability index by 9 %, decrease of total alveolar phospholipids content by 25 % and change of its fraction composition, i.e. decrease of major surface active fraction (phosphatidylcholine) by 68 %, increase of phosphatidic acid amount by 151 % and increase of lisophosphatidylcholine by 163 %. Besides that, experimental ICH is followed by lung edema on the lung blood filling background and increase of blood NO. Fingolimod administration does not affect surfactant surface activity but totally corrects water balance, lung blood filling and blood NO content.

Changes in micro- and central hemodynamic parameters in rats under the action of acetylsalicylic acid and its coordination compounds with metals

Introduction. The cutaneous blood circulation is a representative model both for studying the mechanisms of vascular diseases and for assessing the current state of the central hemodynamics in preclinical researches of various chemical compounds. Aim. The changes in the parameters of cutaneous microcirculation and central hemodynamics (heart rate and blood pressure) were studied in the animals under the action of acetylsalicylic acid and its coordination compounds with cations of cobalt, zinc, nickel and manganese at a dose of 20 mg/kg. Materials and methods. The research was conducted using the laser Doppler flowmetry method on the Lazma-MC device (manufactured by RPE Lazma, Russia) and the NIBP200A system (Biopac Systems, Inc., USA). Results. The study shows that animals develop bradycardia, and microcirculation and central hemodynamics change in two ways after the introduction of acetylsalicylic acid and the tested metal salicylates. These ways are hypotension-related hyperemia (acetylsalicylic acid and cobalt salicylate) and ischemia (zinc, nickel and manganese salicylates) associated with hypertension. Conclusion. The obtained data confirm the cardiotropic activity of new coordination compounds. The data also prove that the generation of the acetylsalicylic acid derivatives allows enhancing it physiological effects, as well as obtaining completely new molecules. The molecules are different from the precursor one and are necessary for the production of effective drugs.

Hypertensive patients features of the microcirculation type after new coronavirus infection of COVID-19

Introduction. The COVID-19 pandemic multiplies the incidence of long-term adverse events. Family history of heart disease predicates the necessity of study hemostasis in hypertensive patients. The purpose was to study the microcirculation in hypertensive COVID-19 survivors. Materials and methods. We selected patients treated at the hospitals of Samara from January to March 2021. COVID-19 survivors (diagnosis was confirmed by polymerase chain reaction analysis) were divided into 2 groups and analysed: the group with family history of hypertension (167 patients) and control group with no relevant past medical history (68 patients). The main microcirculation characteristics were evaluated by laser Doppler flowmetry of skin blood flow. Results. The average age of COVID-19 survivors was 52.3±14.2 years, n=86 (51.4 %) – male. The majority of patients (n=61/36.5 %) were 45 to 54 years. A fifth of the patients (n=35/20.9 %) showed no complaints about the underlying disease, the clinical manifestations of the rest were general weakness, fever, shortness of breath, cough, headaches, unstable blood pressure, inflammation of the ENT organs. By comparison the microcirculation parameters of the case patients and control group, a decreased perfusion was detected. It requires a preventive medicine to prevent from early and distant micro and macrothrombosis. Conclusion. The study of microcirculation essential features by the LDF of skin blood flow revealed a pathological type with a predominance of vasoconstrictions in patients with a history of hypertension. Taking into account the proven increase in the incidence of thrombotic events in COVID-19 survivors, the noticed changes in microcirculation require a new approach to prevent from adverse events concerning the hypercoagulation process, especially in patients with famil y history of heart disease.

Embolism to the main limb arteries in patients with atrial fibrillation

Introduction. Acute limb ischemia due to embolism in patients with atrial fibrillation remains poorly studied. Objective – to study the clinical significance and role of atrial fibrillation (AF) in the development of embolism to the bifurcation of the aorta and the main arteries of the limbs. Materials and methods. Treatment results of 1816 patients with acute ischemia of the extremities due to embolism treated at a specialized vascular surgical department for the past 30 years were analyzed. 1611 (88.7 %) of them had AF. The distribution into studied groups was according to the period time factor. Group 1 (n = 744) consisted of patients admitted in the period from 1991 to 2000; in group 2 (n = 568) – admitted in the period from 2001 to 2010, in group 3 (n = 299) – from 2011 to 2020. Methods included clinical examination, electrocardiography, Doppler-ultrasound, echocardiography. Results. The role of rheumatic heart disease as a cause of AF has decreased over the past decades by almost 10 times (from 19.5 % in group 1 to 2.0 % in group 3). Currently, the main background diseases for the development of AF are arterial hypertension and various forms of coronary artery disease. Embolism in patients with AF may develop in the arteries of all vascular areas of the systemic circulation, but in the practice of a vascular surgeon more often in the main arteries of minor caliber – the brachial (24.5 %) and popliteal (13.0 %). Multiple embolisms to various vascular areas were found in 2.8 % of patients. Urgent surgical revascularization of the limb by open embolectomy was performed in 1481 (91.9 %) patients that allowed 1348 (83.7 %) to be discharged with limb-sparing. Conclusion. In patients with acute limb ischemia of embologenic ethiology, comorbid AF has 88.7 % of them. Urgent embolectomy allows 83.7 % of patients to be discharged without limb amputation. Hospital mortality in the period 1991–2000 was 15.6 %, the last decade has been reduced to 7.4 %.