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    ABSTRACT: The Redox-Optimized ROS Balance [R-ORB] hypothesis postulates that the redox environment [RE] is the main intermediary between mitochondrial respiration and reactive oxygen species [ROS]. According to R-ORB, ROS emission levels will attain a minimum vs. RE when respiratory rate (VO2) reaches a maximum following ADP stimulation, a tenet that we test herein in isolated heart mitochondria under forward electron transport [FET]. ROS emission increased two-fold as a function of changes in the RE (~400 to ~900mV·mM) in state 4 respiration elicited by increasing glutamate/malate (G/M). In G/M energized mitochondria, ROS emission decreases two-fold for RE ~500 to ~300mV·mM in state 3 respiration at increasing ADP. Stressed mitochondria released higher ROS, that was only weakly dependent on RE under state 3. As a function of VO2, the ROS dependence on RE was strong between ~550 and ~350mV·mM, when VO2 is maximal, primarily due to changes in glutathione redox potential. A similar dependence was observed with stressed mitochondria, but over a significantly more oxidized RE and ~3-fold higher ROS emission overall, as compared with non-stressed controls. We conclude that under non-stressful conditions mitochondrial ROS efflux decreases when the RE becomes less reduced within a range in which VO2 is maximal. These results agree with the R-ORB postulate that mitochondria minimize ROS emission as they maximize VO2 and ATP synthesis. This relationship is altered quantitatively, but not qualitatively, by oxidative stress although stressed mitochondria exhibit diminished energetic performance and increased ROS release.
    Biochimica et Biophysica Acta 11/2013;
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    ABSTRACT: Due to potential patient harm, magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices has traditionally been contraindicated. Following the EnRhythm MRI SureScan Study, an MR conditional pacemaker with modified leads was FDA approved. Electrical and handling characteristics of MR conditional pacing leads compared to traditional leads has not been established. To compare short and long term performance of the Medtronic 5086MRI to the Medtronic 5076 lead. Patients (n=466) implanted with two 5086MRI leads (EnRhythm MRI Study) and 316 patients implanted with two 5076 leads in two prospective clinical investigations were analyzed. Electrical characteristics were stable in both groups at implant compared to 12 months and clinically acceptable throughout. Ventricular capture thresholds (V) were slightly higher at 12 months for the 5086MRI lead than the 5076 (0.93±0.47 vs. 0.74±0.42, p<0.001). Ventricular sensing amplitudes (mV) for the 5086MRI were lower at implant (9.0±4.7 vs. 13.9±6.9, p<0.001) and 12 months (9.8±4.8 vs. 15.4±7.5, p<0.001) than 5076. There was no statistical difference in lead handling. At 12 months, the estimated right atrial lead-related complication-free survival rate was 99.3% for 5086MRI vs 99.6% for 5076 (log-rank p=0.65), and the estimated right ventricular lead-related complication-free survival rates were 98.5% vs 100% (log-rank p=0.03). Acute lead dislodgments occurred in 2.6% of patients with 5086MRI compared with 0.6% of patients with 5076 leads (p=0.05). The 5086MRI lead demonstrates clinically acceptable electrical characteristics while providing safe access to MR-guided diagnostics. However, compared to 5076, 5086MRI exhibits lower ventricular sensing, slightly higher ventricular capture thresholds, and higher acute lead dislodgement rate.
    Heart rhythm: the official journal of the Heart Rhythm Society 10/2013;
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    ABSTRACT: Background: Circulating factors delivered to the nodose ganglion (NG) by the occipital artery (OA) have been shown to affect vagal afferent activity, and thus the contractile state of the OA may influence blood flow to the NG. Methods: OA were isolated and bisected into proximal and distal segments relative to the external carotid artery. Results: Bisection highlighted stark differences between maximal contractile responses and OA sensitivity. Specifically, maximum responses to vasopressin and the V1 receptor agonist were significantly higher in distal than proximal segments. Distal segments were significantly more sensitive to 5-hydroxytryptamine (5-HT) and the 5-HT2 receptor agonist than proximal segments. Angiotensin II (AT)2, V2 and 5-HT1B/1D receptor agonists did not elicit vascular responses. Additionally, AT1 receptor agonists elicited mild, yet not significantly different maximal responses between segments. Conclusion: The results of this study are consistent with contractile properties of rat OA being mediated via AT1, V1 and 5-HT2 receptors and dependent upon the OA segment. Furthermore, vasopressin-induced constriction of the OA, regardless of a bolus dose or a first and second concentration-response curve, retained this unique segmental difference. We hypothesize that these segmental differences may be important in the regulation of blood flow through the OA in health and disease. © 2013 S. Karger AG, Basel.
    Journal of Vascular Research 10/2013; 50(6):478-485.
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    ABSTRACT: Recent legislation requires reducing Medicare payments to hospitals with higher than expected 30-day readmission rates, but there is no consensus strategy to identify patients who should optimally be targeted with care coordination services to mitigate this risk. To determine which hospital and patient factors predict variation in all discharge hospital readmission rates, a 5% sample of all Medicare fee-for-service beneficiaries with continuous Part A and B coverage was examined for the first 9 months of 2008 in combination with other administrative data available to the Centers for Medicare and Medicaid Services. We included age, sex, race, dual-eligibility status, number of comorbid conditions, geographic region, hospital case mix, and reason for entitlement in the multiple regression model to assess how they influenced the 30-day readmission rate. Beneficiaries with 10 or more chronic conditions were more than 6 times more likely to be readmitted than beneficiaries with 1 to 4 chronic conditions. These beneficiaries represent only 8.9% of all Medicare beneficiaries (31.0% of all hospitalizations), but they were responsible for 50.2% of all readmissions. The 31.8% of beneficiaries with 5 to 9 chronic conditions (55.5% of all hospitalizations) had the second highest odds ratio (2.5) and were responsible for 45% of all readmissions. Journal of Hospital Medicine 2013. © 2013 Society of Hospital Medicine. Journal of Hospital Medicine 2013. © 2013 Society of Hospital Medicine.
    Journal of Hospital Medicine 08/2013;
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    ABSTRACT: Syncope is a risk factor for sudden cardiac death (SCD) in many conditions associated with structural heart disease as well as inherited heart disease. The ECG in patients with syncope should be examined carefully for signs of structural heart disease, such as myocardial infarction or cardiomyopathy; signs of conduction system disease, such as bundle branch block or atrioventricular block; and signs of primary electrical disease. Important forms of cardiomyopathy accompanied by ECG changes include hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular dysplasia (ARVD/C). Common ECG findings in HCM include left ventricular hypertrophy by voltage, repolarization abnormalities, QRS widening, pseudoinfarction patterns, and slurred QRS upstroke mimicking delta waves. Classical ECG findings of ARVD/C include T-wave inversions and epsilon waves in the right precordial leads (V1-V3). Important forms of primary electrical disease which may result in syncope include Wolff-Parkinson-White syndrome, long QT syndrome, and Brugada syndrome, which is characterized by coved ST-segments in the right precordial leads, associated with a history of syncope, ventricular arrhythmia, or sudden cardiac death in probands or family member. There are three Brugada ECG patterns; however, only type I (spontaneous or induced) is considered diagnostic. Recently, studies have suggested that patients with J-point elevation or early repolarization pattern on ECG are at elevated risk of SCD. The clinical significance of finding early repolarization in a patient with syncope is unknown and should be a subject of future research.
    Journal of electrocardiology 08/2013;
  • Journal of the American College of Cardiology 08/2013;
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    ABSTRACT: Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk. Multi-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7) , height(2.7) , or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities. Left ventricular mass by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, P < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76. Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
    Echocardiography 08/2013;
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    ABSTRACT: Sudden cardiac death (SCD) is a major public health concern, accounting for 400,000 deaths in the US each year. Clinical and autopsy studies have consistently demonstrated a predominant, common pathophysiology in Western populations, showing that the most common electrophysiological mechanism of SCD is ventricular fibrillation, and the most common pathologic substrate is coronary heart disease (CHD). In about half of SCD cases, death is the first clinical manifestation of CHD. Yet risk factors of SCD early in the natural history of conditions predisposing SCD have not been fully identified, and SCD risk stratification strategy in the general population has not been developed. ECG is an easily available, non-expensive and non-invasive tool, which carries valuable information on electrophysiological properties of the heart. However, traditional analysis of ECG includes very limited assessment of the arrhythmogenic substrate. In this review rationale for development of ECG SCD risk score for screening in the general population is discussed.
    Journal of electrocardiology 08/2013;
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    ABSTRACT: We examined whether there is a relationship between repolarization abnormalities on electrocardiography (EKG) and deformation abnormalities by echocardiography. Analysis of baseline EKGs and mechanical (echo-based deformation) changes was performed in 128 patients with a clinical diagnosis of hypertrophic cardiomyopathy (HCM). Patients with left ventricular hypertrophy (LVH) or repolarization abnormalities had higher septal thickness when compared to patients with normal EKG. Patients with EKG evidence of LVH or QTc prolongation had lower systolic velocity, systolic strain, systolic strain rate, late diastolic velocity, and late diastolic strain rate than patients with a normal EKG. Patients with strain pattern or ST depression/T-wave inversion had lower systolic velocity, systolic strain, systolic strain rate, early diastolic velocity, and late diastolic velocity when compared to patients with normal EKGs. LVH and repolarization abnormalities on surface EKG are markers of impaired systolic and diastolic mechanics in HCM.
    Journal of Cardiovascular Translational Research 06/2013;
  • Heart rhythm: the official journal of the Heart Rhythm Society 05/2013;
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