The effects of polyunsaturated fatty acids and antioxidant vitamins on atrial oxidative stress, nitrotyrosine residues, and connexins following extracorporeal circulation in patients undergoing cardiac surgery

Abstract

Cardiac surgery with extracorporeal circulation is characterized by different degrees of myocardial ischemia/reperfusion, which is often associated with postoperative atrial fibrillation (POAF). We have previously shown that a novel preventive therapy based on the reinforcement of the antioxidant system using omega-3 fatty acids plus antioxidant vitamin supplementation applied to patients undergoing cardiac surgery reduces POAF occurrence. We hypothesized that oxidative stress and nitrosative stress are involved in the development of an arrhythmogenic substrate by their effect on connexins (Cx40, Cx43 and Cx45) abundance and distribution pattern. Therefore, we have assessed the effect of redox status on atrial tissue in patients undergoing cardiac surgery. Placebo/POAF and supplemented/POAF patients showed 276 and 170% higher reactive oxygen species (ROS) levels and 223 and 96% higher nitrotyrosine residues levels, respectively, compared to sinus rhythm (SR). In POAF tissue, antioxidant supplementation prevented Cx40 and Cx43 lateralization on cardiomyocyte sarcolemma, keeping them at the intercalated disks. POAF samples showed Cx40 heterogeneous distribution pattern, presenting tissue areas lacking this protein (49 and 55% lower levels in placebo/POAF and supplemented/POAF groups, respectively, compared to SR). Of note, Cx45 overexpression occurred in POAF, being 211 and 167% higher in placebo/POAF and supplemented/POAF groups, respectively, compared to SR. It is concluded that treatment with omega-3 fatty acids and antioxidant vitamins reduces oxidative and nitrosative stress and prevents Cx40/Cx43 lateralization in atrial tissue likely contributing to POAF prevention. However, it failed to fully prevent POAF occurrence because these compounds have no effects on the normalization of Cx40 down-regulation and Cx45 up-regulation, which may promote POAF.

Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs

“…In addition, it has been reported recently that treatment with omega-3 PUFA and antioxidant vitamins reduces oxidative and nitrosative stress and prevents Cx40/Cx43 lateralization in human atrial tissue, which likely contributes to POAF prevention. However, it failed to fully prevent POAF occurrence, due to the fact that these compounds did not normalize Cx40 down-regulation and Cx45 up-regulation, that may promote POAF [ 85 ].…”

“…It appears that the anti-arrhythmic effect of beta-adrenergic blockers (often used in heart disease patients) may interfere with the anti-arrhythmic effect of omega-3 PUFAs. An attenuation of an abnormal Cx43 distribution by omega-3 PUFAs resulted in a reduction in POAF incidence [ 85 ].…”

Evaluation of in vitro anti-oxidant and anti-inflammatory activities of Korean and Chinese Lonicera caerulea

“…Oxidative stress is induced by reactive oxygen species (ROS) that can damage cells and result in diseases such as diabetes, cardiovascular ailments, cancer, and liver damage [ 5 ]. Anti-oxidant vitamins and enzymes, such as superoxide dismutase, glutathione peroxidase, and glutathione reductase, can reduce excessive ROS production [ 6 ]. Phytochemicals with distinct flavors, odors, and colors can also exhibit anti-oxidant activities, and it has been reported that berries contain many phytochemicals such as a flavonoids, anthocyanins, and phenolic acids [ 7 ].…”

microRNA-223-3p attenuates angiotensin II-dependent ROS effect on cell viability by targeting NLRP3 in H9c2 cells

“…In detail, oxidative stress is involved in the mechanism of AF in the following three aspects: atrial electrical remodeling, structural remodeling and connexin remodeling. [23][24][25][26] Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is a serine threonine kinase and can be oxidized by ROS at methionine residues 281/282 and then transform to ox-CaMKII which is associated with cardiovascular disease. 27 Additionally, ox-CaMKII was identified as a proarrhythmic signal because of promoting delayed afterdepolarizations (DADs) in Ang II infusion.…”