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Abstract

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, chi2 test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 +/- 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06-0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated. 2007 S. Karger AG, Basel

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Hazards of postoperative atrial arrhythmias.

M J Rosenbloom, R Schuessler, Carla Cox … (1993)

Between January 1, 1986, and December 31, 1991, 4,507 adult patients underwent cardiac surgical procedures requiring cardiopulmonary bypass. Of these patients, 3,983 patients who did not undergo operation for supraventricular tachycardia and who were in normal sinus rhythm preoperatively form the study group for the present study. Postoperatively, all patients were monitored continuously for the development of arrhythmias until the time of hospital discharge. The incidence of atrial arrhythmias requiring treatment for the most commonly performed operative procedures were as follows: coronary artery bypass grafting, 31.9%; coronary artery bypass grafting and mitral valve replacement, 63.6%; coronary artery bypass grafting and aortic valve replacement, 48.8%; and heart transplantation, 11.1%. For all patients considered collectively, the risk factors associated with an increased incidence of postoperative atrial arrhythmias (p < 0.05 by multivariate logistic regression) included increasing patient age, preoperative use of digoxin, history of rheumatic heart disease, chronic obstructive pulmonary disease, and increasing aortic cross-clamp time. Postoperative atrial fibrillation was associated with an increased incidence of postoperative stroke (3.3% versus 1.4%; p < 0.0005), increased length of hospitalization in the intensive care unit (5.7 versus 3.4 days; p = 0.001) and postoperative nursing ward (10.9 versus 7.5 days; p = 0.0001), increased incidence of postoperative ventricular tachycardia or fibrillation (9.2% versus 4.0%; p < 0.0005), and an increased need for placement of a permanent pacemaker (3.7% versus 1.6%; p < 0.0005). These data provide a basis for targeting specific patient subgroups for prospective, randomized trials of therapeutic modalities designed to decrease the incidence of postoperative atrial arrhythmias.

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Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

C A Carnes, M Chung, T Nakayama … (2001)

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.

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Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

Andreas Goette, Thorsten Staack, Christoph Röcken … (2000)

The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF). Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear. Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques. Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.

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PubMed ID:: 17008797

DOI:: 10.1159/000095936

ScienceOpen disciplines: Chemistry

Keywords: Aged,Aged, 80 and over,Atrial Appendage,pathology,Atrial Fibrillation,surgery,Coronary Artery Bypass,adverse effects,Female,Fibrosis,Humans,Hypertrophy,Male,Middle Aged,Myocardium,Postoperative Complications

Histologic assessment of right atrial appendage myocardium in patients with atrial fibrillation after coronary artery bypass graft surgery.

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Karger: Cardiovascular System

Most cited references 16

Hazards of postoperative atrial arrhythmias.

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.

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