In this trial, perioperative statin therapy did not prevent postoperative atrial fibrillation or perioperative myocardial damage in patients undergoing elective cardiac surgery. Acute kidney injury was more common with rosuvastatin. (Funded by the British Heart Foundation and others; STICS ClinicalTrials.gov number, NCT01573143.).
Background-An altered nitric oxide-redox balance has been implicated in the pathogenesis of atrial fibrillation (AF).Statins inhibit NOX2-NADPH oxidases and prevent postoperative AF but are less effective in AF secondary prevention; the mechanisms underlying these findings are poorly understood. Methods and Results-By using goat models of pacing-induced AF or of atrial structural remodeling secondary to atrioventricular block and right atrial samples from 130 patients undergoing cardiac surgery, we found that the mechanisms responsible for the NO-redox imbalance differ between atria and with the duration and substrate of AF. Rac1 and NADPH oxidase activity and the protein level of NOX2 and p22phox were significantly increased in the left atrium of goats after 2 weeks of AF and in patients who developed postoperative AF in the absence of differences in leukocytes infiltration. Conversely, in the presence of longstanding AF or atrioventricular block, uncoupled nitric oxide synthase activity (secondary to reduced BH 4 content and/or increased arginase activity) and mitochondrial oxidases accounted for the biatrial increase in reactive oxygen species. Atorvastatin caused a mevalonate-reversible inhibition of Rac1 and NOX2-NADPH oxidase activity in right atrial samples from patients who developed postoperative AF, but it did not affect reactive oxygen species, nitric oxide synthase uncoupling, or BH 4 in patients with permanent AF. Key Words: atrial fibrillation Ⅲ free radicals Ⅲ nitric oxide synthase Ⅲ oxidative stress Ⅲ statins A trial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with significantly increased morbidity and mortality. 1 A striking feature of AF is its ability to sustain itself by inducing a number of electric and structural changes in the atrial myocardium, which in turn promote AF maintenance and increase vulnerability to relapse. 2 Although the process of AF-induced atrial remodeling and its role in begetting AF have been described in great detail in animal models of atrial tachyarrhythmia and in human AF, 2 the underlying mechanisms that result in these electric and structural changes remain unclear. Emerging data indicate that an altered nitric oxide (NO)-redox balance in the atrial myocardium may be implicated in the pathogenesis of AF and AF-induced atrial remodeling. In particular, in human and experimental atrial tachyarrhythmia, increased atrial production of reactive oxygen species (ROS) and reduced NO bioavailability are associated with atrial remodeling and increased vulnerability to AF, 3-7 both of which can be prevented by agents that decrease myocardial oxidative stress and inflammation. [7][8][9] In humans, NOX2-containing NADPH oxidases are the main source of ROS production in both right atrial (RA) homogenates and isolated myocytes, 6 and RA NADPH-stimulated superoxide production is independently associated with an increased risk of developing AF after cardiac surgery. 10 Statins prevent AF-induced early electric remodeling in dogs 9 and reduce the...
There is a strong independent association between myocardial O(2)(-)/ONOO(-) and in-hospital complications after cardiac surgery. Both myocardial O(2)(-) and ONOO(-) are reduced by pre-operative statin treatment, through a Rac1-mediated suppression of NADPH oxidase activity. These findings suggest that inhibition of myocardial NADPH oxidases may contribute to the beneficial effect of statins in patients undergoing cardiac surgery. (Effects of Atorvastatin on Endothelial Function, Vascular and Myocardial Redox State in High Cardiovascular Risk Patients; NCT01013103).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.