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

Mitochondria 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 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 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.

Association between alcohol consumption and systolic ventricular function: a population-based study.

BACKGROUND: Although moderate alcohol consumption is associated with decreased clinical heart failure, there are no population-based studies evaluating the relationship between alcohol consumption and left ventricular (LV) systolic function. We sought to evaluate the relationship between alcohol consumption and LV systolic function in the community. METHODS: In a population-based random sample of 2,042 adults, age ≥45 years, we assessed alcohol consumption by a self-administered questionnaire. Responders were categorized by alcohol consumption level: abstainer, former drinker, light drinker (<1 drink a day), moderate drinker (1-2 drinks a day), and heavy drinker (>2 drinks a day). Systolic function was assessed by echocardiography. RESULTS: We identified 38 cases of systolic dysfunction in 182 abstainers, 309 former drinkers, 1,028 light drinkers, 251 moderate drinkers, and 146 heavy drinkers. A U-shaped relationship was observed between alcohol consumption and moderate systolic dysfunction (LV ejection fraction [LVEF] ≤40%), with the lowest prevalence in light drinkers (0.9%) compared to the highest prevalence in heavy drinkers (5.5%) (odds ratio 0.14, 95% CI 0.04-0.43). This association persisted across different strata of risk factors of systolic dysfunction as well as in multivariate analysis. No significant association between alcohol consumption and systolic function was seen in subjects with LVEF >50% or ≤50%. CONCLUSIONS: There is a U-shaped relationship between alcohol consumption volume and LVEF, with the lowest risk of moderate LV dysfunction (LVEF ≤40%) observed in light drinkers (<1 drink a day). These findings are parallel to the relationship between alcohol consumption and cardiovascular disease prevalence.

Free vascularized lymph node transfer for treatment of lymphedema: A systematic evidence based review.

BACKGROUND: Free vascularized lymph node transfer (VLNT) is a relatively novel technique for treatment of lymphedema. The purpose of this systematic review was to evaluate the current evidence on VLNT and to determine if there is objective data concerning improved outcomes. METHODS: A literature search of PubMed, EMBASE and CENTRAL electronic databases was conducted to identify articles written in the English language on VLNT for treatment of lymphedema. Publications were selected according to inclusion criteria. Papers reporting adjunct techniques and those that did not describe outcomes were excluded. Data including patient demographics, surgical technique, complications and outcomes were extracted. A quality score was calculated for each article. RESULTS: Eighteen studies were included with an overall study population of 305 patients. Mean quality score of articles was 5.3 with levels of evidence range from II to IV. Among 182 patients who underwent limb circumference assessment, 165 (91%) showed postoperative improvement. Reduction of limb volume was noted in 98 of 114 (86%) patients. Ninety two patients underwent lymphoscintigraphy/lymphangiography and 55 (60%) demonstrated moderate or significant improvement of flow. Patient satisfaction was questioned in 105 patients and with exception of 7 patients, all reported a high satisfaction level with significant relief in symptoms and improved quality of life. Publications also reported a reduction in infectious episodes. CONCLUSION: VLNT appears to provide improvement in lymphedema. More studies with standardized methods for reporting outcomes and uniform patient selection are needed to evaluate this technique thoroughly.