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physiology of heart failure

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https://www.readbyqxmd.com/read/28429185/high-content-assessment-of-cardiac-function-using-heart-on-a-chip-devices-as-drug-screening-model
#1
Genevieve Conant, Benjamin Fook Lun Lai, Rick Xing Ze Lu, Anastasia Korolj, Erika Yan Wang, Milica Radisic
Drug discovery and development continues to be a challenge to the pharmaceutical industry despite great advances in cell and molecular biology that allow for the design of better targeted therapeutics. Many potential drug compounds fail during the clinical trial due to inefficacy and toxicity that were not predicted during preclinical stages. The fundamental problem lies with the use of traditional drug screening models that still largely rely on the use of cell lines or animal cell monolayers, which leads to lack of predictive power of human tissue and organ response to the drug candidates...
April 20, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28425435/fret-biosensor-uncovers-camp-nano-domains-at-%C3%AE-adrenergic-targets-that-dictate-precise-tuning-of-cardiac-contractility
#2
Nicoletta C Surdo, Marco Berrera, Andreas Koschinski, Marcella Brescia, Matias R Machado, Carolyn Carr, Peter Wright, Julia Gorelik, Stefano Morotti, Eleonora Grandi, Donald M Bers, Sergio Pantano, Manuela Zaccolo
Compartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and myofilament sites, reveals differential kinetics and amplitudes of localized cAMP signals...
April 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28424575/contribution-of-autonomic-reflexes-to-the-hyperadrenergic-state-in-heart-failure
#3
REVIEW
Edgar Toschi-Dias, Maria Urbana P B Rondon, Chiara Cogliati, Nazareno Paolocci, Eleonora Tobaldini, Nicola Montano
Heart failure (HF) is a complex syndrome representing the clinical endpoint of many cardiovascular diseases of different etiology. Given its prevalence, incidence and social impact, a better understanding of HF pathophysiology is paramount to implement more effective anti-HF therapies. Based on left ventricle (LV) performance, HF is currently classified as follows: (1) with reduced ejection fraction (HFrEF); (2) with mid-range EF (HFmrEF); and (3) with preserved EF (HFpEF). A central tenet of HFrEF pathophysiology is adrenergic hyperactivity, featuring increased sympathetic nerve discharge and a progressive loss of rhythmical sympathetic oscillations...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28420470/-explore-objective-clinical-variables-for-detecting-delirium-in-icu-patients-a-prospective-case-control-study
#4
Xiaojiang Liu, Jie Lyu, Youzhong An
OBJECTIVE: The aim of this case-control study is to explore clinical objective variables for diagnosing delirium of intensive care unit (ICU) patients. METHODS: According to the method of prospective case-control study, critical adult postoperative patients who were transferred to ICU of Peking University People's Hospital from October 2015 to May 2016 and needed mechanical ventilation were included. After evaluating the Richmond agitation sedation scale score (RASS), the patients whose score were -2 or greater were sorted into two groups, delirium and non-delirium, according to the confusion assessment method for the ICU (CAM-ICU)...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28417963/loop-diuretics-affect-skeletal-myoblast-differentiation-and-exercise-induced-muscle-hypertrophy
#5
Shintaro Mandai, Susumu Furukawa, Manami Kodaka, Yutaka Hata, Takayasu Mori, Naohiro Nomura, Fumiaki Ando, Yutaro Mori, Daiei Takahashi, Yuki Yoshizaki, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Yasuro Furuichi, Nobuharu L Fujii, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416103/a-new-twist-on-right-heart-failure-with-left-ventricular-assist-systems
#6
EDITORIAL
Brian A Houston, Keyur B Shah, Mandeep R Mehra, Ryan J Tedford
Despite significant efforts to predict and prevent right heart failure, it remains a leading cause of morbidity and mortality after implantation of left ventricular assist systems (LVAS). In this Perspective, we review the underappreciated anatomic and physiologic principles that govern the relationship between left and right heart function and contribute to this phenomenon. This includes the importance of considering the right ventricle (RV) and pulmonary arterial circuit as a coupled system; the contribution of the left ventricle (LV) to RV contractile function and the potential negative impact of acutely unloading the LV; the influence of the pericardium and ventricular twist on septal function; the role of RV deformation in reduced mechanical efficiency after device placement; and the potential of ongoing stressors of an elevated right-sided preload...
March 24, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28414037/spatio-temporal-regulation-of-connexin43-phosphorylation-and-gap-junction-dynamics
#7
REVIEW
Joell L Solan, Paul D Lampe
Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP3) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases...
April 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28413968/hypertension-and-heart-failure-with-preserved-ejection-fraction-connecting-the-dots
#8
Costas Tsioufis, Georgios Georgiopoulos, Dimitrios Oikonomou, Costas Thomopoulos, Niki Katsiki, Alexandros Kasiakogias, Christina Chrysochoou, Dimitrios Konstantinidis, Theodoros Kalos, Dimitrios Tousoulis
Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF...
April 14, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28413612/advances-in-understanding-the-renin-angiotensin-aldosterone-system-raas-in-blood-pressure-control-and-recent-pivotal-trials-of-raas-blockade-in-heart-failure-and-diabetic-nephropathy
#9
REVIEW
Lama Ghazi, Paul Drawz
The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the physiology of blood pressure control and the pathophysiology of hypertension (HTN) with effects on vascular tone, sodium retention, oxidative stress, fibrosis, sympathetic tone, and inflammation. Fortunately, RAAS blocking agents have been available to treat HTN since the 1970s and newer medications are being developed. In this review, we will (1) examine new anti-hypertensive medications affecting the RAAS, (2) evaluate recent studies that help provide a better understanding of which patients may be more likely to benefit from RAAS blockade, and (3) review three recent pivotal randomized trials that involve newer RAAS blocking agents and inform clinical practice...
2017: F1000Research
https://www.readbyqxmd.com/read/28410579/assessing-the-usability-by-clinicians-of-vision-a-hierarchical-display-of-patient-collected-physiological-information-to-clinicians
#10
Cubby L Gardner, Fang Liu, Paul Fontelo, Michael C Flanagan, Albert Hoang, Harry B Burke
BACKGROUND: The inability of patients to accurately and completely recount their clinical status between clinic visits reduces the clinician's ability to properly manage their patients. One way to improve this situation is to collect objective patient information while the patients are at home and display the collected multi-day clinical information in parallel on a single screen, highlighting threshold violations for each channel, and allowing the viewer to drill down to any analog signal on the same screen, while maintaining the overall physiological context of the patient...
April 14, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28406991/a-mathematical-model-for-active-contraction-in-healthy-and-failing-myocytes-and-left-ventricles
#11
Li Cai, Yongheng Wang, Hao Gao, Yiqiang Li, Xiaoyu Luo
Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model...
2017: PloS One
https://www.readbyqxmd.com/read/28403121/pheochromocytoma-crisis-in-icu-a-french-multicenter-cohort-study-with-emphasis-on-rescue-extracorporeal-membrane-oxygenation
#12
Bertrand Sauneuf, Nicolas Chudeau, Benoit Champigneulle, Claire Bouffard, Marion Antona, Nicolas Pichon, David Marrache, Romain Sonneville, Antoine Marchalot, Camille Welsch, Antoine Kimmoun, Bruno Bouchet, Elmi Messai, Sylvie Ricome, David Grimaldi, Jonathan Chelly, Jean-Luc Hanouz, Alain Mercat, Nicolas Terzi
OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males...
April 11, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28402745/effect-of-ularitide-on-cardiovascular-mortality-in-acute-heart-failure
#13
Milton Packer, Christopher O'Connor, John J V McMurray, Janet Wittes, William T Abraham, Stefan D Anker, Kenneth Dickstein, Gerasimos Filippatos, Richard Holcomb, Henry Krum, Aldo P Maggioni, Alexandre Mebazaa, W Frank Peacock, Mark C Petrie, Piotr Ponikowski, Frank Ruschitzka, Dirk J van Veldhuisen, Lisa S Kowarski, Mark Schactman, Johannes Holzmeister
Background In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis. Methods In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy...
April 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28402148/should-modulation-of-p50-be-a-therapeutic-target-in-the-critically-ill
#14
Amudan J Srinivasan, Clare Morkane, Daniel S Martin, Ian J Welsby
A defining feature of human hemoglobin is its oxygen binding affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), and the variability of this parameter over a range of physiological and environmental states. Modulation of this property of hemoglobin can directly affect the degree of peripheral oxygen offloading and tissue oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen affinity in normal and abnormal physiology and discusses the current state of the literature regarding artificial modulation of p50...
April 12, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28401511/deep-phenotyping-of-systemic-arterial-hemodynamics-in-hfpef-part-2-clinical-and-therapeutic-considerations
#15
Julio A Chirinos
Multiple phase III trials over the last few decades have failed to demonstrate a clear benefit of various pharmacologic interventions in heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF). Therefore, a better understanding of its pathophysiology is important. An accompanying review describes key technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. This review deals with the potential of this approach to enhance our clinical, translational, and therapeutic approach to HFpEF...
April 11, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28400916/angiotensin-receptor-blocker-drugs-and-inhibition-of-adrenal-beta-arrestin-1-dependent-aldosterone-production-implications-for-heart-failure-therapy
#16
EDITORIAL
Anastasios Lymperopoulos, Beatrix Aukszi
Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated...
March 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28399617/heart-failure-and-role-of-circulating-mmp-2-and-mmp-9
#17
Jana Radosinska, Miroslav Barancik, Norbert Vrbjar
The myocardial extracellular matrix (ECM) is the dynamic environment that is fundamental for the structural and physiological homeostasis of the heart. Alterations in ECM homeostasis may lead to diastolic or systolic dysfunction and consequent development of heart failure (HF). For degradation of ECM, matrix metalloproteinases (MMPs) are responsible. To the most frequently analyzed MMPs in relation to HF syndrome belong MMP-2 and MMP-9. This review summarizes the recent knowledge concerning the role of circulating MMP-2 and MMP-9 (i...
April 11, 2017: Panminerva Medica
https://www.readbyqxmd.com/read/28392700/urinary-cadmium-levels-predict-mortality-of-patients-with-acute-heart-failure
#18
Ching-Wei Hsu, Cheng-Hao Weng, Cheng-Chia Lee, Dan-Tzu Lin-Tan, Pao-Hsien Chu, Kuan-Hsing Chen, Tzung-Hai Yen, Wen-Hung Huang
BACKGROUND: Acute heart failure (AHF) is a serious condition that is associated with increased mortality in critically ill patients. Previous studies indicated that environmental exposure to cadmium increases mortality of general populations. However, the relationship of cadmium exposure and mortality is unclear for AHF patients. MATERIALS AND METHODS: A total of 153 patients with AHF in intensive care units (ICUs) met the inclusion criteria and were followed up for 6 months...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28392102/creatine-phosphate-administration-in-cell-energy-impairment-conditions-a-summary-of-past-and-present-research
#19
REVIEW
A V Gaddi, P Galuppo, J Yang
BACKGROUND: Creatine phosphate (CrP) plays a fundamental physiological role by providing chemical energy for cell viability and activity, especially in muscle tissue. Numerous pathological conditions, caused by acute or chronic ischaemic situations, are related to its deficiency. For these reasons, it has been used as a cardioprotective agent in heart surgery and medical cardiology for many years. OBJECTIVE: This article gives a brief overview of the main characteristics of exogenous CrP...
March 14, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28390796/handle-with-care-a-systematic-review-on-frailty-in-cardiac-care-and-its-usefulness-in-heart-transplantation
#20
REVIEW
Oliver Mauthner, Veerle Claes, Mieke Deschodt, Sunita R Jha, Sandra Engberg, Peter S Macdonald, Phillip J Newton, Sabina De Geest
BACKGROUND: There is growing consensus that frailty, a state of vulnerability and a decline in functioning across multiple physiological body systems, is a valuable criterion to guide clinicians' risk prediction for poor outcomes in adult transplant candidates. In its 2016 listing criteria for heart transplantation the International Society for Heart Lung Transplantation recommends frailty assessment. We aimed to summarize the usefulness of frailty assessment in heart transplant candidates or recipients reported throughout the literature...
March 30, 2017: Transplantation Reviews
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