Aim. To assess the complex dynamics of the main parameters of cardiovascular status and serum markers of endothelial dysfunction (ED) in patients with rheumatoid arthritis (RA), who were treated with infliximab.Material and methods. The main group (MG) included 50 patients with seropositive RA, who received a combination of methotrexate and infliximab. The examination took place at baseline, as well as two, six, and 14 weeks after the treatment started. Comparison groups (CG) included healthy volunteers (n=25) and RA patients treated with methotrexate only (n=110). Serum levels of tumor necrosis factor-α (TNO-α), interleukin-10 (IL-10), tissue plasminogen activator (TPA), and von Willebrand factor (vWf) were measured, using ELISA. Left ventricular (LV) function and microvascular status were assessed with echocardiography and laser Doppler flowmetry (LDF), respectively.Results. The E/A ratio was reduced in all subgroups, and at Week 14 of infliximab therapy, it slightly increased. At baseline, LDF parameters, such as neurogenic arteriole tone and intravascular resistance, were increased. Infliximab therapy was associated with a moderate decline of these parameters. Throughout the study, serum vWf concentration was higher in MG patients than in healthy controls. TPA activity was reduced at baseline (496±173 pg/ml), increasing at Week 14 up to 705±157 pg/ml. Baseline concentrations of TNF-α and UL-10 were substantially elevated (357,1±34 and 453±42 pg/ml, respectively). At Week 6, TNF-α concentration decreased significantly. At Week 14, not only TNF-α level decreased, reaching 94±28 pg/ml, but also the ratio TNF-α/IL-10 decreased (from 0,78±0,5 to 0,4±0,2).Conclusion. In RA patients, infliximab was highly effective for the functional cytokine dysbalance correction, also demonstrating pleiotropic effects, such as correction of microvascular and endothelial dysfunction.

Цель исследования - создание на основе анализа нарушений механизмов системы регуляции артериального давления (АД) нового методологического подхода в определении эффективности антигипертензивной терапии у пациентов с гипертонической болезнью. Методика. В исследование включены данные 277 пациентов (136 мужчин, 141 женщина) с гипертонической болезнью II стадии 1-2 степени, риск II, III. Возраст пациентов 58,6±6,4 лет, давность заболевания 7,2±1,4 лет. В группу контроля вошли 57 практически здоровых лиц (25 женщин, 32 мужчины) в возрасте 52,1±4,4 года. После скрининга и получения письменного информированного согласия в виде монотерапии назначены: небиволол, лизиноприл, лозартан, индапамид, амлодипин, и нефиксированная комбинация лизиноприла и индапамида. Изучены изменения показателей АД на выделенных уровнях системы регуляции АД после 6 мес терапии. Результаты. Оценка эффективности применяемой терапии показала, что при стабилизации артериального давления у пациентов всех 6 групп на должном уровне существенные различия выявлены на интегративном уровне регуляции. При применении амлодипина, лозартана, лизиноприла, а также комбинации лизиноприла и индапамида регуляторно-адаптивные возможности организма улучшились, при лечении индапамидом - не изменились, при применении небиволола снизились. Предложена оригинальная классификация уровней регуляции (контроля) артериального давления у человека, основанная на общебиологическом принципе иерархической организации регуляции вегетативных функций. Выделены уровни: интегративный, вегетативного обеспечения (осуществляемый автономной нервной системой), органный, периферический (эндотелиально-микроциркуляторный). Заключение. Количественная оценка на интегративном уровне является универсальным показателем эффективности лечения, что открывает возможность создания методологического подхода, основанного на оценке влияния терапевтических воздействий не только на орган- или функцию-мишень, но и на состояние организма как целостной системы. Aim. To create a new methodological approach for determining the effectiveness of antihypertensive therapy in patients with arterial hypertension based on the analysis of violation of mechanisms in the blood pressure (BP) regulation system. Methods. This study included 277 patients (136 males, 141 females) with stage II, grade 1-2 hypertension, risk II, III, aged 58.6±6.4 yrs, with disease duration 7.2±1.4 yrs. The control group included 57 essentially healthy individuals (25 females, 32 males) aged 52.1±4.4 yrs. After screening and obtaining written informed consent, the following monotherapy was prescribed: nebivolol, lisinopril, losartan, indapamide, and amlodipine, plus an unfixed combination of lisinopril and indapamide. Changes in BP indexes at the predetermined levels of the BP regulation system were studied after 6 mos. of treatment. Results. Evaluation of the therapy effectiveness showed that, when BP was stabilized in all six groups at proper values, significant differences were revealed at the integrative regulatory level. When patients were treated with amlodipine, losartan, lisinopril, as well as a combination of lisinopril and indapamide, the regulatory and adaptive capabilities of the body improved. When treated with indapamide, these capabilities were unchanged, and when treated with nebivolol, these capabilities decreased. A new classification of the regulatory levels of BP control in humans is proposed. This classification is based on the general biological principle of hierarchical organization for the regulation of autonomic functions. The following levels are distinguished: integrative, autonomic support, i.e., carried out by the autonomic nervous system, organ, and peripheral, i.e., endothelial-microcirculatory. Conclusion. Quantitative assessment at the integrative level is a universal indicator of the treatment effectiveness. It makes it possible to create a methodological approach to determine possible effectiveness of treatment based on the assessed impact not only on the target organ or function, but also on the status of the body as a whole system.