Performing cardiac surgery under cardiopulmonary bypass (CPB) and circulatory arrest (CA) provokes the development of complications caused by tissue metabolism, microcirculatory disorders, and endogenous nitric oxide (NO) deficiency. This study aimed to investigate the potential mechanisms for systemic organoprotective effects of exogenous NO during CPB and CA based on the assessment of dynamic changes in glycocalyx degradation markers, deformation properties of erythrocytes, and tissue metabolism in the experiment. A single-center prospective randomized controlled study was conducted on sheep, n = 24, comprising four groups of six in each. In two groups, NO was delivered at a dose of 80 ppm during CPB (“CPB + NO” group) or CPB and CA (“CPB + CA + NO”). In the “CPB” and “CPB + CA” groups, NO supply was not carried out. NO therapy prevented the deterioration of erythrocyte deformability. It was associated with improved tissue metabolism, lower lactate levels, and higher ATP levels in myocardial and lung tissues. The degree of glycocalyx degradation and endothelial dysfunction, assessed by the concentration of heparan sulfate proteoglycan and asymmetric dimethylarginine, did not change when exogenous NO was supplied. Intraoperative delivery of NO provides systemic organoprotection, which results in reducing the damaging effects of CPB on erythrocyte deformability and maintaining normal functioning of tissue metabolism.

Aim      To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment. Material and methods The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity. Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= –0.54; р<0.05) and with left ventricular myocardial mass (LVMM) (r= –0.36; р<0.05) at two years of follow-up whereas beta-ARM delta at one week was interrelated with the renin concentration in the long-term (r= –0.44; р<0.05). At two years, the content of beta-ARM was increased in both groups. Conclusion The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

Aim. To identify the associations between beta-adrenergic reactivity of erythrocytes and the progression of heart failure (HF) in patients after myocardial infarction (MI).Material and methods. The study included 50 patients with HF and history of MI 6 months ago. To determine the level of sympathoadrenal system activity, we analyzed beta-adrenergic reactivity by changing the osmotic resistance of erythrocytes by use of adrenoceptor blocking agent.Results. The frequency of HF progression after index MI was 26% (n=13). All patients were divided into 2 groups depending on the presence/absence of HF progression in the postinfarction period. When determining beta-adrenergic reactivity, it was found that patients with HF progression compared with patients without it had the higher level of beta-adrenergic reactivity of membrane (β-ARM) of erythrocytes: 58,8 (50,9; 78,0) CU and 46,8 (38,0; 66,3) CU, p=0,025). A ROC analysis made it possible to establish the β-ARM level ≥49,53 CU a cut-off point, which can be considered as a marker of HF progression in patients after MI (sensitivity 92,3%, specificity 62,2%). This level of β-ARM is associated with a more than five-fold increase of HF progression risk in patients after MI (OR 5,48; 95% CI 1,28-23,37; p=0,024).Conclusion. In patients with HF and MI history, there is a decrease in the adrenergic reactivity of erythrocyte cell membrane, which is reflected by an increase of β-ARM above normal range of 20 CU. At the same time, β-ARM in patients with HF progression compared with patients without it is significantly increased. Established cut-off point of β-ARM (≥49,53 CU) allows predicting the HF progression with high sensitivity and specificity.

Introduction. Patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) are characterized by sympathetic hyperactivity. A promising method for the assessment is a measurement of erythrocyte membrane beta-adrenergic reactivity (β-ARM). However, little is known about β-ARM in patients with RHTN and T2DM.Purpose. To investigate the properties of β-ARM of erythrocytes in patients with RHTN and T2DM in relation to clinical, laboratory, and instrumental data.Material and Methods. The cross-sectional study comprised 38 patients with RHTN combined with T2DM with mean age of 62.1 ± 7 years (25 women (65.8%)), 24-hour systolic/diastolic blood pressure (24-BP) (SBP/DBP) of 160.3 ± 14.2/90.8 ± 10.5 mm Hg, and glycated hemoglobin (HbA1c) of 7.2 ± 1.4%. The comparison group comprised 24 patients with RHTN without T2DM, which did not significantly differ in sex and age. General clinical examinations, measurements 24-BP and office blood pressure, β-ARM, HbA1c, 24-hour urine, echocardiography, and 24-hour electrocardiography with the assessment of heart rate variability (HRV) with low-frequency (LF) and high-frequency (HF) components were performed in all patients.Research Results. In both groups, β-ARM was significantly higher than the normal value corresponding to 20 conventional units (CU): 45.9 ± 21.9 and 41.3 ± 18.9 for patients with RHTN+T2DM and RHTN without T2DM, respectively, p = 0.39. The incidence of increase in β-ARM was comparable: 82% in RHTN with T2DM patients and 88% in RHTN without T2DM patients, χ2 = 0.38, p = 0.537. The β-ARM values correlated with duration of hypertension (R = 0.31), SBP-24 variability (R = 0.36), LF (R = 0.60), and HF (R = –0.53)) values according to HRV, 24-hour urine volume (R = –0.32), left ventricular parameters (ejection fraction (R = 0.42), ventricular efficiency (R = –0.36), arterioventricular coupling (R = –0.40)), duration of T2DM (R = –0.45), and HbA1c level (R = –0.55).Conclusions. RHTN patients were characterized by a high frequency of β-ARM increase, whether or not T2DM was present, although a long and severe course of T2DM was associated with lower values of this indicator. According to the data from instrumental studies, β-ARM in patients with RHTN and T2DM was quantitatively related to the markers of sympathetic activity, which correlated with the duration of hypertension and parameters of renal and left ventricular functional status.