Neurohormonal Activation In Heart Failure Research Articles

The historical evolution of knowledge of the involvement of neurohormonal systems in the pathophysiology and treatment of heart failure

Our knowledge of the pathophysiology of heart failure (HF) underwent profound changes during the 1980s. Once thought to be of exclusively structural origin, HF began to be seen as the consequence of hormonal imbalance. A number of seminal studies were published in that decade focusing on the impact of neurohormonal activation in HF. Presently, eight neurohormonal systems are known to have a key role in HF development: four stimulate vasoconstriction and sodium/water retention (the sympathetic nervous system, the renin-angiotensin-aldosterone system [RAAS], endothelin, and the vasopressin-arginine system), while the other four stimulate vasodilation and natriuresis (the prostaglandin system, nitric oxide, the dopaminergic system, and the natriuretic peptide system [NPS]). These systems are strongly interconnected and are subject to intricate regulation, functioning together in a delicate homeostasis. Disruption of this homeostasis is characteristic of HF. This review explores the historical development of knowledge on the impact of the neurohormonal systems on HF pathophysiology, from the first studies to current understanding. In addition, the therapeutic potential of each of these systems is discussed, and currently used neurohormonal antagonists are characterized. Special emphasis is given to the latest drug approved for use in HF with reduced ejection fraction, sacubitril/valsartan. This drug combines two different molecules, acting on two different systems (RAAS and NPS) simultaneously.

Noninvasive Urea Monitoring Using a Flexible Electrochemical Sweat Based Sensor

With the development of technology in healthcare systems, interest in a wearable, portable, and even implantable device is growing, allowing health indicators to be read by direct skin contact [1], [2]. The non-invasive sensing platform overcomes the inconvenience of the conventional monitoring system and enabling easy and quick medical diagnosis in real time [3]. Urea is a major metabolite of the human body in a form of nitrogen, a key biomarker above the renal failure, dehydration, and hepatic issues [4], [5]. Urea detection is conceivable from serum, urine, and sweat in the body. The concentration of urea in the sweat is higher than that of serum so sweat based urea sensor can substitute the current pricking test method [6]. Higher levels of urea in sweat are also essential notices because they are correlated with uremia [7]. To sense the non-electric active of urea, the present method uses an enzyme in electrochemical sensors. The enzyme-based sensor consists of an enzyme (urease) and a mediator, which distinguishes the urease-catalyzed hydrolysis products [8]. However, the enzymatic sensor is complex, unstable, and costly, so non-enzyme sensors are better suited for wearable sensor devices. Nickel-based catalysts with nanostructures, large surface area, good electrical conductivity, and low cost are the best nominees for urea detection as they oxidize urea without enzymes [9]. Recently, a polymer-type substrate has been utilized for the flexible and wearable sensor device which requires porous and conductive polymers. Herein, we investigated a facile approach to form nickel oxyhydroxide with metal (metal-NiOOH) based flexible electrochemical sensor by electrospinning method. The morphology and the structure of the metal-NiOOH catalysts were observed using transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. The metal-NiOOH catalysts with polymer showed excellent flexibility and competent linear sensitivity to urea electrooxidation in the physiological concentration area. A comprehensive investigation of the performances regarding metal-NiOOH as a catalyst in a sweat-based sensor will be presented. References Feiner, Ron, et al. "Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function." Nature materials 15.6 (2016): 679. Liu, Yuhao, Matt Pharr, and Giovanni Antonio Salvatore. "Lab-on-skin: a review of flexible and stretchable electronics for wearable health monitoring." ACS nano 11.10 (2017): 9614-9635. Pickup, John C., et al. "In vivo glucose monitoring: the clinical reality and the promise." Biosensors and Bioelectronics 20.10 (2005): 1897-1902. D'Apolito, Maria, et al. "Urea-induced ROS cause endothelial dysfunction in chronic renal failure." Atherosclerosis 239.2 (2015): 393-400. Thudichum, J. L. W. "On the analysis of urea in urine for clinical purposes." British medical journal 1.38 (1857): 788 Stefaniak, Aleksandr B., and Christopher J. Harvey. "Dissolution of materials in artificial skin surface film liquids." Toxicology in Vitro 20.8 (2006): 1265-1283. Kazory, Amir. "Emergence of blood urea nitrogen as a biomarker of neurohormonal activation in heart failure." The American journal of cardiology 106.5 (2010): 694-700. Liu, Yan-Ling, et al. "Flexible electrochemical urea sensor based on surface molecularly imprinted nanotubes for detection of human sweat." Analytical chemistry 90.21 (2018): 13081-13087. Mahshid, Sahar Sadat, et al. "Template-based electrodeposition of Pt/Ni nanowires and its catalytic activity towards glucose oxidation." Electrochimica Acta 58 (2011): 551-555. Acknowledgement This work was supported by Agency for Defense Development (ADD) as global cooperative research for high performance and light weight bio-urine based fuel cell (UD160050BD) and the Ocean University of China-Auburn University (OUC-AU) Grants program.

Neurohormonal activation in heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) develops when cardiac output falls as a result of cardiac injury. The most well-recognized of the compensatory homeostatic responses to a fall in cardiac output are activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS). In the short term, these 'neurohormonal' systems induce a number of changes in the heart, kidneys, and vasculature that are designed to maintain cardiovascular homeostasis. However, with chronic activation, these responses result in haemodynamic stress and exert deleterious effects on the heart and the circulation. Neurohormonal activation is now known to be one of the most important mechanisms underlying the progression of heart failure, and therapeutic antagonism of neurohormonal systems has become the cornerstone of contemporary pharmacotherapy for heart failure. In this Review, we discuss the effects of neurohormonal activation in HFrEF and highlight the mechanisms by which these systems contribute to disease progression.

Neprilysin Inhibitors: Emerging Therapy for Heart Failure

Biologically active natriuretic peptides (NPs) are an integral part of cardiac homeostasis as they help to maintain sodium and fluid balance. When homeostasis is perturbed by neurohormonal activation in heart failure, levels of NPs rise in response. Neprilysin (NEP) is a naturally occuring enzyme that breaks down NPs. Scientists have recently discovered a novel pharmacologic agent that combines a NEP inhibitor and an angiotensin receptor blocker. In a large clinical trial, this new drug was found to reduce hospitalization and mortality in systolic heart failure. The challenges of implementing this therapy include patient selection, cost, and risk of side effects including angioedema and Alzheimer's disease.

Current Concepts of Neurohormonal Activation in Heart Failure

Neurohormonal activation is a commonly cited array of phenomena in the body’s physiologic response to heart failure. Although various neurohormones and pharmacologic agents that moderate their pathophysiologic effects have been reviewed in the nursing literature, both the mechanisms of neurohormonal system activation and cellular and organ system effects have been described only in brief. Accordingly, this article reviews mechanisms of neurohormonal activation and describes cellular and cardiovascular effects of the (1) sympathetic nervous system, (2) renin-angiotensin-aldosterone system, (3) kallikrein-kininogen-kinin system, (4) vasopressinergic system, (5) natriuretic peptide systems, and (6) endothelin in the context of heart failure. This article implicitly details the physiologic basis for numerous current and potential future pharmacologic agents used in the management of heart failure. It is intended that this article be used as a reference for advanced clinical nursing practice, research, and education.

Current Concepts of Neurohormonal Activation in Heart Failure

Neurohormonal activation is a commonly cited array of phenomena in the body's physiologic response to heart failure. Although various neurohormones and pharmacologic agents that moderate their pathophysiologic effects have been reviewed in the nursing literature, both the mechanisms of neurohormonal system activation and cellular and organ system effects have been described only in brief. Accordingly, this article reviews mechanisms of neurohormonal activation and describes cellular and cardiovascular effects of the (1) sympathetic nervous system, (2) renin-angiotensin-aldosterone system, (3) kallikrein-kininogen-kinin system, (4) vasopressinergic system, (5) natriuretic peptide systems, and (6) endothelin in the context of heart failure. This article implicitly details the physiologic basis for numerous current and potential future pharmacologic agents used in the management of heart failure. It is intended that this article be used as a reference for advanced clinical nursing practice, research, and education.

Current Concepts of Neurohormonal Activation in Heart Failure

Current Concepts of Neurohormonal Activation in Heart Failure

Novel Strategies: Challenge Loop Diuretics and Sodium Management in Heart Failure—Part II

The conflicting results of diuretic treatments in heart failure (HF) and the importance of Na management in the context of the cardiorenal syndrome and neurohormonal activation in HF have suggested novel and counterintuitive strategies, focused primarily on the use of vasopressin antagonists and hypertonic saline solution with high doses of loop diuretics and their neurohormonal interference. The emerging novel therapies involving direct inhibition of vasopressin receptors appear to show promising results. The use of hypertonic saline solution mixed with a high dose of loop diuretics produces, probably by indirect mechanisms, a reduction or inhibition of the activated neurohormonal systems in HF patients. This treatment opens a new window on the role of sodium management in these patients and on the relation between sodium and the kidney's role and function in heart failure. The authors review the current evidence for these therapies and suggest hypothetical bases for their efficacy.

Prognostic markers in heart failure—congestion, neurohormones, and the cardiorenal syndrome

There are several markers of poor prognosis in heart failure (HF). The most established markers of poor prognosis in HF include neurohormonal (NH) imbalance, low ejection fraction (EF), ventricular arrhythmias, intraventricular conduction delays, low functional capacity, low SBP, and renal failure. The relative importance of these factors is unknown, as they have never been studied together. We present a 74-year-old female with nonischemic cardiomyopathy and an EF<20% who over 24 years since diagnosis, never developed clinical or hemodynamic congestion, was never hospitalized for HF, and never required a loop diuretic. She had all of the clinical indicators of poor prognosis in HF except for severe NH imbalance and renal failure, illustrating their importance in HF prognosis. While NH activation in HF is initially an adaptive mechanism, an imbalance of NH effectors causes congestion leading to a vicious cycle of congestion, renal dysfunction, and worsening of HF. The combination of NH activation and renal failure in HF is a vasomotor nephropathy known as the cardiorenal syndrome (CRS) and portends a poor prognosis. Pharmacological disruption of NH pathways early in HF may prevent CRS and, therefore, improve outcomes.

The Role of Brain Natriuretic Peptide in Systolic Heart Failure

Heart failure (HF) is a progressive multisystem disease that involves neurohormonal activation, dysfunction of cardiac and skeletal musculature, and a host of other pathological changes. The neurohormonal activation in HF triggers the release of the natriuretic peptides. One peptide of particular interest is brain natriuretic peptide (BNP). It is primarily released by the ventricles of the heart and has adaptive function in counteracting the effects of neurohormonal activation in patients with HF. The focus of this article is the discussion of the physiology of BNP as well as its role in systolic HF, although it also plays a role in diastolic HF.

Effect of metoprolol on heart rate variability in patients with heart failure

Background: Patients with heart failure(HF) apresented depresssed heart rate variability(HRV) as a marker of the severity of the disease.Beta-blocker therapy is believed to modulate the detrimental effect of overcompensating neurohormonal activation in HF and reverse autonomic dysfunction with improvement of the HRV. Objective: The aim of this study was evaluated the effects of metoprolol on HRV in patients with HF before and after three and six months of metoprolol combined therapy. Methods: We studied 102 consecutive patients with HF(65 men, age 60±14 years,), mean LVEF 29,84±1,61% by ventriculography radioisotopic, and New York Heart Association (NYHA) class II to IV. Twenty-four holter recording were performed before and after 3 and 6 months. HRV parameters were calculated in the time domain.

Clinical Use of Markers of Neurohormonal Activation in Heart Failure

Chronic heart failure secondary to ventricular dysfunction is characterized by neurohormonal activation, reflected mainly as increased sympathetic and renin-angiotensin system activation. Increased plasma levels of several neurohormones have been associated with increased morbidity and mortality. Neurohormone activation is part of the mechanism of compensation that is activated to maintain hemodynamic stability when heart output is reduced. Despite the initial benefits of this mechanism, neurohormone activation has been shown to contribute to progressive impairment of ventricular function and symptoms of heart failure, such that the greater the degree of activation, the worse the prognosis.Despite their important implications for prognosis, plasma neurohormone levels are not measured in clinical practice as part of the clinical evaluation of patients with heart failure. Medical treatment with ACE inhibitors and beta blockers, by lowering the plasma levels of some neurohormones, reduces their prognostic usefulness in establishing risk. Thus, no ideal biomarker is yet available that is stable and easy to measure, and that accurately established risk in patients with heart failure. Such a marker should also have an acceptable cost/benefit ratio.

Endothelin in neurohormonal activation in heart failure.

Endothelin in neurohormonal activation in heart failure.

Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group.

There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p less than 0.05), aldosterone (p = 0.003), noradrenaline (p less than 0.001), adrenaline (p = 0.001), and atrial natriuretic factor (p = 0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular.