Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.

Ethan J. Anderson, Jimmy T. Efird, Stephen W. Davies, Wesley T. O'Neal, Timothy M. Darden, Kathleen A. Thayne, Lalage A. Katunga, Linda C. Kindell, T. Bruce Ferguson, Curtis A. Anderson, W. Randolph Chitwood, Theodore C. Koutlas, J. Mark Williams, Evelio Rodriguez, Alan P. Kypson

    Research output: Contribution to journalArticle

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    Abstract

    Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.

    Original languageEnglish (US)
    JournalJournal of the American Heart Association
    Volume3
    Issue number1
    DOIs
    StatePublished - Jan 1 2014

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    Monoamine Oxidase
    Atrial Fibrillation
    Oxidation-Reduction
    Myocardium
    Confidence Intervals
    Peroxidase
    Enzymes
    Thoracic Surgery
    Reactive Oxygen Species
    Oxidoreductases
    Atrial Appendage
    Quality of Health Care
    NADPH Oxidase
    Glutathione
    Patient Care
    Mitochondria
    Biomarkers

    All Science Journal Classification (ASJC) codes

    • Cardiology and Cardiovascular Medicine

    Cite this

    Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation. / Anderson, Ethan J.; Efird, Jimmy T.; Davies, Stephen W.; O'Neal, Wesley T.; Darden, Timothy M.; Thayne, Kathleen A.; Katunga, Lalage A.; Kindell, Linda C.; Ferguson, T. Bruce; Anderson, Curtis A.; Chitwood, W. Randolph; Koutlas, Theodore C.; Williams, J. Mark; Rodriguez, Evelio; Kypson, Alan P.

    In: Journal of the American Heart Association, Vol. 3, No. 1, 01.01.2014.

    Research output: Contribution to journalArticle

    Anderson, EJ, Efird, JT, Davies, SW, O'Neal, WT, Darden, TM, Thayne, KA, Katunga, LA, Kindell, LC, Ferguson, TB, Anderson, CA, Chitwood, WR, Koutlas, TC, Williams, JM, Rodriguez, E & Kypson, AP 2014, 'Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.', Journal of the American Heart Association, vol. 3, no. 1. https://doi.org/10.1161/JAHA.113.000713
    Anderson, Ethan J. ; Efird, Jimmy T. ; Davies, Stephen W. ; O'Neal, Wesley T. ; Darden, Timothy M. ; Thayne, Kathleen A. ; Katunga, Lalage A. ; Kindell, Linda C. ; Ferguson, T. Bruce ; Anderson, Curtis A. ; Chitwood, W. Randolph ; Koutlas, Theodore C. ; Williams, J. Mark ; Rodriguez, Evelio ; Kypson, Alan P. / Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation. In: Journal of the American Heart Association. 2014 ; Vol. 3, No. 1.
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    abstract = "Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95{\%} confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95{\%} CI=0.99 to 4.3; Q4: ARR=3.8, 95{\%} CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95{\%} confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95{\%} CI=0.36 to 1.1; Q4: ARR=0.56, 95{\%} CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.",
    author = "Anderson, {Ethan J.} and Efird, {Jimmy T.} and Davies, {Stephen W.} and O'Neal, {Wesley T.} and Darden, {Timothy M.} and Thayne, {Kathleen A.} and Katunga, {Lalage A.} and Kindell, {Linda C.} and Ferguson, {T. Bruce} and Anderson, {Curtis A.} and Chitwood, {W. Randolph} and Koutlas, {Theodore C.} and Williams, {J. Mark} and Evelio Rodriguez and Kypson, {Alan P.}",
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    T1 - Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.

    AU - Anderson, Ethan J.

    AU - Efird, Jimmy T.

    AU - Davies, Stephen W.

    AU - O'Neal, Wesley T.

    AU - Darden, Timothy M.

    AU - Thayne, Kathleen A.

    AU - Katunga, Lalage A.

    AU - Kindell, Linda C.

    AU - Ferguson, T. Bruce

    AU - Anderson, Curtis A.

    AU - Chitwood, W. Randolph

    AU - Koutlas, Theodore C.

    AU - Williams, J. Mark

    AU - Rodriguez, Evelio

    AU - Kypson, Alan P.

    PY - 2014/1/1

    Y1 - 2014/1/1

    N2 - Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.

    AB - Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high-risk patients, remains elusive. Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH-peroxidase (GPx) and GSH-reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10-fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.

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