Atrial fibrillation: Mechanistic insights and treatment options

Mathew, Sumi; Patel, Jigar; Joseph, Satheesh

doi:10.1016/j.ejim.2009.07.011

Cited by 66 publications

(54 citation statements)

References 120 publications

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“…Atrial enlargement has been recognized as a hallmark of AF [2,21]. In the present study, the LAV max and LAV min of the total LA were significantly higher in the PAF group compared to the control group and in the PeAF group compared to the PAF group, which was consistent with the results obtained in previous studies [22,23].…”

Section: Functional Assessment Of the La In Af Patientssupporting

confidence: 95%

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Assessment of the structural remodeling of the left atrium by 64-multislice cardiac CT: Comparative studies in controls and patients with atrial fibrillation

Park

Jung

et al. 2012

International Journal of Cardiology

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Section: Functional Assessment Of the La In Af Patientssupporting

confidence: 95%

“…In patients with atrial fibrillation (AF), mechanical remodeling of the LA manifests as decreased atrial contractility and increased atrial compliance, which leads to LA enlargement [2]. Radiofrequency ablation (RFA) has emerged as an important interventional procedure for the restoration of normal sinus rhythms in AF patients [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the structural remodeling of the left atrium by 64-multislice cardiac CT: Comparative studies in controls and patients with atrial fibrillation

Park

Jung

et al. 2012

International Journal of Cardiology

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“…Cardiac surgery is a common procedure with a significant incidence of post-operative complications associated with increased morbidity and several complications which have few effective therapies [1][2][3][4]. In addition, cardiac surgery inevitably results in varying degrees of cardiac ischaemia, trauma and introduction of blood and other foreign material into the pericardial compart- Abbreviations: (BHI), Bioenergetic health index; DMEM, dulbecco's modified eagle's medium; (ECAR), extracellular acidification rate; MAS, mannitol and sucrose; OCR, oxygen consumption rate; (PBMC), peripheral blood mononuclear cell; (PO-PCF), post-operative pericardial fluid; (ROS), reactive oxygen species; RPMI, Roswell Park Memorial Institute; (OCR), oxygen consumption rate.…”

Section: Introductionmentioning

confidence: 99%

Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients

et al. 2015

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SynopsisMonitoring the bioenergetics of leucocytes is now emerging as an important approach in translational research to detect mitochondrial dysfunction in blood or other patient samples. Using the mitochondrial stress test, which involves the sequential addition of mitochondrial inhibitors to adherent leucocytes, we have calculated a single value, the Bioenergetic Health Index (BHI), which represents the mitochondrial function in cells isolated from patients. In the present report, we assess the BHI of monocytes isolated from the post-operative blood and post-operative pericardial fluid (PO-PCF) from patients undergoing cardiac surgery. Analysis of the bioenergetics of monocytes isolated from patients' PO-PCF revealed a profound decrease in mitochondrial function compared with monocytes isolated from their blood or from healthy controls. Further, patient blood monocytes showed no significant difference in the individual energetic parameters from the mitochondrial stress test but, when integrated into the BHI evaluation, there was a significant decrease in BHI compared with healthy control monocytes. These data support the utility of BHI measurements in integrating the individual parameters from the mitochondrial stress test into a single value. Supporting our previous finding that the PO-PCF is pro-oxidant, we found that exposure of rat cardiomyocytes to PO-PCF caused a significant loss of mitochondrial membrane potential and increased reactive oxygen species (ROS). These findings support the hypothesis that integrated measures of bioenergetic health could have prognostic and diagnostic value in translational bioenergetics.

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“…The incidence and prevalence of AF increase with advancing age and aging-associated diseases such as hypertension, ischemic heart disease, and heart failure (2, 40) and contribute to increased morbidity, particularly an increased risk for stroke, heart failure, and death (25,52). Although the pathophysiology of AF has been well characterized, the underlying mechanisms that contribute to the progression of AF in human atria have not been fully defined (33,35,57,58,60). Mitochondria, occupying 30% of cardiomyocyte volume, are critical for maintaining normal energetics of the heart, a highly aerobic organ dependent on oxidative phosphorylation (OXPHOS) for maintenance of its normal electrical and mechanical function (1, 61).…”

mentioning

confidence: 99%

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation

Emelyanova

Ashary

Cosic

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation. Am J Physiol Heart Circ Physiol 311: H54 -H63, 2016. First published May 6, 2016 doi:10.1152/ajpheart.00699.2015Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 Ϯ 0.007 vs. 0.09 Ϯ 0.006 nmol·min Ϫ1 ·citrate synthase activity Ϫ1 , P ϭ 0.02) and II (0.11 Ϯ 0.012 vs. 0.16 Ϯ 0.012 nmol·min Ϫ1 ·citrate synthase activity Ϫ1 , P ϭ 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 Ϯ 0.027 vs. 0.12 Ϯ 0.01 nmol·min Ϫ1 ·citrate synthase activity Ϫ1 , P ϭ 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 Ϯ 17 vs. 11 Ϯ 2 arbitrary units, P ϭ 0.03) and 4-hydroxynonenal level (77.64 Ϯ 30.2 vs. 9.83 Ϯ 2.83 ng·mg Ϫ1 protein, P ϭ 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF. atrial fibrillation; humans; mitochondria; electron transport chain complexes; oxidative phosphorylation; oxidative stress; superoxide; 4-hydroxynonenal protein adducts NEW & NOTEWORTHYThe study provides evidence of a selective downregulation of mitochondrial electron transport chain functional activity predominantly affecting complexes I and II and associated increase ATRIAL FIBRILLATION (AF), a rapid irregular rhythm of the atria, is associated with electrical, functional, and structural changes in the atria that promote the substrate for its recurrence and progression (36, 53, 60). The incidence and prevalence of AF increase with advancing age and aging-associated diseases such as hypertension, ischemic heart disease, and heart failure (2, 40) and contribute to increased morbidity, particularly an increased risk for stroke, heart failure, and death (25,52). Although the pathophysiology of AF has been well characterized, the underlying mechanisms that contribute to the progression of AF in human atria have not been fully defined (33,35,57,58,60). Mitochondria, occupying 30% ...

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Atrial fibrillation: Mechanistic insights and treatment options

Cited by 66 publications

References 120 publications

Assessment of the structural remodeling of the left atrium by 64-multislice cardiac CT: Comparative studies in controls and patients with atrial fibrillation

Assessment of the structural remodeling of the left atrium by 64-multislice cardiac CT: Comparative studies in controls and patients with atrial fibrillation

Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation

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