digoxin and Sleep-Apnea--Obstructive

Heart failure (HF) is a syndrome characterized by upregulation of the sympathetic nervous system and abnormal responsiveness of the parasympathetic nervous system. Studies in the 1980s and 1990s demonstrated that inhibition of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors improved symptoms and mortality in HF resulting from systolic dysfunction, thus providing a framework to consider the use of β-blockers for HF therapy, contrary to the prevailing wisdom of the time. Against this backdrop, this article reviews the contemporary understanding of the sympathetic nervous system and the failing heart.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Afferent Pathways; Angiotensin Receptor Antagonists; Autonomic Nervous System Diseases; Brain; Cardiac Imaging Techniques; Cardiotonic Agents; Digoxin; Efferent Pathways; Exercise Therapy; Exercise Tolerance; Forecasting; Heart Failure; Humans; Kidney Failure, Chronic; Muscle, Skeletal; Myocardial Infarction; Norepinephrine; Oxidative Stress; Polymorphism, Genetic; Receptors, Adrenergic; Receptors, Adrenergic, beta; Reflex; Renin-Angiotensin System; Sleep Apnea, Obstructive; Sympathetic Nervous System

ACC Stage C heart failure includes those patients with prior or current symptoms of heart failure in the context of an underlying structural heart problem who are primarily managed with medical therapy. Although there is guideline-based medical therapy for those with heart failure with reduced ejection fraction (HFrEF), therapies in heart failure with preserved ejection fraction (HFpEF) have thus far proven elusive. Emerging therapies such as serelaxin are currently under investigation and may prove beneficial. The role of advanced surgical therapies, such as mechanical circulatory support, in this population is not well defined. Further investigation is warranted for these therapies in patients with Stage C heart failure.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiotonic Agents; Coronary Artery Bypass; Defibrillators, Implantable; Diet, Sodium-Restricted; Digoxin; Diuretics; Exercise Therapy; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Mitral Valve Insufficiency; Obesity; Patient Compliance; Patient Education as Topic; Sleep Apnea, Obstructive; Vasodilator Agents

The role of hypoxia-inducible factor (HIF)-1 in pancreatic β-cell response to intermittent hypoxia (IH) was examined. Studies were performed on adult wild-type (WT), HIF-1α heterozygous (HET), β-cell-specific

Topics: Animals; Digoxin; Disease Models, Animal; Glucose; Heterozygote; Hydrogen Peroxide; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NADPH Oxidase 4; Oxygen; RNA, Small Interfering; Sleep Apnea, Obstructive; Transcriptional Activation

Recent studies have provided evidence that hypoxia may stimulate the release of endogenous digitalislike factors (EDLF). Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep and may be associated with sympathetic activation and a high risk of developing hypertension. This study was designed to measure EDLF in the plasma of patients with OSA diagnosed by polysomnography, with patients being classified by the number of apneic-hypopneic episodes/h sleep (apnea-hypopnea index, AHI). Plasma was obtained in the morning from 8 male normotensive OSA patients (OSA-N) (AHI 70+/-6), 2 untreated hypertensive OSA patients (OSA-HT), and 11 age-matched healthy male controls (C). EDLFs of different hydrophobicities were separated from the same plasma sample by solid-state C18-cartridges with 25% acetonitrile (ACN) (EDLF-1) followed by 40% ACN (EDLF-2). This procedure recovered ouabain in the first fraction and digoxin and digoxigenin in the second. EDLF was quantified in pM ouabain-equivalents by a human placenta radioreceptor assay. EDLF-1 levels were similar for OSA-N and C (231+/-55 vs. 258+/-58), whereas EDLF-2 levels were increased in OSA-N (244+/-51 vs. 110+/-25 in C, p=0.02). Norepinephrine was increased in apneics. The two OSA-HT had EDLF and norepinephrine levels similar to OSA-N. These preliminary results suggest that OSA is associated with an increase in the more hydrophobic EDLF levels in both normotensive and hypertensive states. No significant increase was found for the less hydrophobic ouabain-like EDLF.

Topics: Adult; Cardenolides; Chromatography, High Pressure Liquid; Digoxin; Humans; Hypertension; Hypoxia; Male; Middle Aged; Saponins; Sleep Apnea, Obstructive