Effect of inhaled nitric oxide on intestinal integrity in cardiopulmonary bypass and circulatory arrest simulation: An experimental study.

Background and Aims: Cardiopulmonary bypass (CPB) and circulatory arrest (CA) can induce intestinal injury and consequently lead to multiple organ dysfunction. Nitric oxide (NO) has protective effects, but its effect on the intestine has not been studied. The study aimed to investigate intestinal injury variables and prove the intestinal protective effects of exogenous nitric oxide when modelling CPB and CA in an experiment. Methods: The study was performed on sheep (n = 24). There were four groups: CPB, CPB + NO, CPB + CA and CPB + CA + NO. Sheep in NO groups received intraoperative inhalation of NO at a dose of 80 ppm. Groups without NO underwent CPB and CA without NO delivery. Defaecation rate, dynamics of intestinal fatty acid binding protein (i-FABP), coefficient of microviscosity and polarity in the areas of lipid-lipid and protein-lipid interactions of erythrocyte membranes were assessed. One hour after CPB, the intestinal tissue was collected and assessed for tissue concentrations of adenosine triphosphate (ATP) and lactate. Results: The defaecation rate after CPB was higher in the CPB + NO group than in the CPB group. The concentration of i-FABP after CPB was lower in the CPB + NO and CPB + CA + NO groups than in the CPB and CPB + CA groups. Erythrocyte deformability before and after CPB revealed no significant dynamics in groups with NO. The ATP concentration 1 h after CPB was higher in the CPB + NO group than in the CPB group. The morphological picture in groups with NO was better. Conclusion: When modelling CPB and CA, NO had a positive effect on the functional and structural state of the intestine and also maintained erythrocyte deformability.

Potential Mechanisms for Organoprotective Effects of Exogenous Nitric Oxide in an Experimental Study.

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.

Expression of the ß1-adrenergic receptor (ADRB1) gene in the myocardium and ß-adrenergic reactivity of the body in patients with a history of myocardium infraction.

ß1-adrenergic receptors (ß1-AR) directly affect on intracardiac hemodynamic and the ability of the heart to tolerate physical activity by regulating its inotropic and chronotropic functions. Severe hypersympathicotonia, specific to coronary artery disease (CAD) and chronic heart failure (HF), leads to impaired functioning of ß1-AR. The aim of this research was to assess the expression level of the ß1-AR ADRB1 gene in the myocardium, to evaluate the ß-adrenergic reactivity of the membrane (ß-ARM) of erythrocytes, and to analyze the association of these parameters with myocardial contractile dysfunction in patients with a myocardial infarction (MI) in the past and without it. The study included 126 patients with chronic CAD. Among the patients, 55.6 % had a history of MI at least 6 months ago. The expression of the ADRB1 gene was assessed using real-time polymerase chain reaction. With this purpose, we isolated RNA from the right atrial appendage, which was excised when a heart-lung machine was connected during a planned coronary bypass surgery. ß-ARM was evaluated in 57 patients. This method is based on the fact of inhibition of hemolysis of erythrocytes, placed in a hyposmotic medium, in the presence of a ß-blocker. Within the whole sample of patients, the expression of the ADRB1 gene is comparable in different functional classes of HF. There was no linear correlation between the expression of the ADRB1 gene and left ventricle ejection fraction (LVEF). In patients with a history of MI, the expression of the ADRB1 gene was elevated when compared to a group of patients without MI (p = 0.017). Patients with a history of MI had higher values of ß-ARM than those without MI (p = 0.017). The reverse correlation between ß-ARM and LVEF (r = -0,570, p = 0,002) was revealed in the group of patients without MI but not in the group of patients with a history of MI (r = -0,137, p = 0,479). In the sample of patients with chronic CAD, in the myocardium of subjects with a history of MI, the relative expression of ADRB1 gene was higher compared to the group of patients without MI. In patients with different functional classes (FC) of HF and with different ejection fraction, both with MI and without it, ADRB1 gene expression was comparable. In the group of patients with a history of MI, an increase in ß-ARM was observed, i.e. decrease in the number or sensitivity of ß-AR. Among patients without MI, an inverse correlation was found between ß-ARM and LVEF.