The Nephroprotective Effect of Nitric Oxide during Extracorporeal Circulation: An Experimental Study.

This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO2 and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

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.