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Cardiac Contractility Modulation

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https://www.readbyqxmd.com/read/29754812/a-randomized-controlled-trial-to-evaluate-the-safety-and-efficacy-of-cardiac-contractility-modulation
#1
William T Abraham, Karl-Heinz Kuck, Rochelle L Goldsmith, JoAnn Lindenfeld, Vivek Y Reddy, Peter E Carson, Douglas L Mann, Benjamin Saville, Helen Parise, Rodrigo Chan, Phi Wiegn, Jeffrey L Hastings, Andrew J Kaplan, Frank Edelmann, Lars Luthje, Rami Kahwash, Gery F Tomassoni, David D Gutterman, Angela Stagg, Daniel Burkhoff, Gerd Hasenfuß
OBJECTIVES: The authors sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. BACKGROUND: CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period...
May 5, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29744528/device-therapy-in-heart-failure-with-reduced-ejection-fraction-cardiac-resynchronization-therapy-and-more
#2
D Duncker, C Veltmann
In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology...
May 9, 2018: Herz
https://www.readbyqxmd.com/read/29732439/rad-gtpase-deletion-attenuates-post-ischemic-cardiac-dysfunction-and-remodeling
#3
Janet R Manning, Lakshman Chelvarajan, Bryana M Levitan, Catherine N Withers, Prabhakara R Nagareddy, Christopher M Haggerty, Brandon K Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A Andres, Jonathan Satin
The protein Rad interacts with the LTCC to modulate trigger Ca2+ , hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction (AMI). Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given a safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling...
February 2018: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29714134/medicinal-chemistry-of-potassium-channel-modulators-an-update-of-recent-progress-2011-2017
#4
Vivek K Vyas, Palak Parikh, Jonali Ramani, Manjunath Ghate
BACKGROUND: Potassium (K+) channels participate in many physiological processes, cardiac function, cell proliferation, neuronal signaling, muscle contractility, immune function, hormone secretion, osmotic pressure, changes in gene expression, and are involved in critical biological functions, and in a variety of diseases. Potassium channels represent a large family of tetrameric membrane proteins. Potassium channels activation reduces excitability, whereas channel inhibition increases excitability...
April 30, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29697870/long-term-results-of-combined-cardiac-contractility-modulation-and-subcutaneous-defibrillator-therapy-in-patients-with-heart-failure-and-reduced-ejection-fraction
#5
Susanne Röger, Boris Rudic, Ibrahim Akin, Tetyana Shchetynska-Marinova, Fabian Fastenrath, Erol Tülümen, Volker Liebe, Ibrahim El-Battrawy, Stefan Baumann, Jürgen Kuschyk, Martin Borggrefe
BACKGROUND: Cardiac contractility modulation (CCM) is an electrical-device therapy for patients with heart failure with reduced ejection fraction (HFrEF). Patients with left ventricular ejection fraction (LVEF) ≤35% also have indication for an implantable cardioverter-defibrillator (ICD), and in some cases subcutaneous ICD (S-ICD) is selected. HYPOTHESIS: CCM and S-ICD can be combined to work efficaciously and safely. METHODS: We report on 20 patients with HFrEF and LVEF ≤35% who received CCM and S-ICD...
April 26, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29695980/cardiac-remodeling-endothelial-cells-have-more-to-say-than-just-no
#6
REVIEW
Vincent F M Segers, Dirk L Brutsaert, Gilles W De Keulenaer
The heart is a highly structured organ consisting of different cell types, including myocytes, endothelial cells, fibroblasts, stem cells, and inflammatory cells. This pluricellularity provides the opportunity of intercellular communication within the organ, with subsequent optimization of its function. Intercellular cross-talk is indispensable during cardiac development, but also plays a substantial modulatory role in the normal and failing heart of adults. More specifically, factors secreted by cardiac microvascular endothelial cells modulate cardiac performance and either positively or negatively affect cardiac remodeling...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29695452/ppar%C3%AE-agonist-pioglitazone-reverses-pulmonary-hypertension-and-prevents-right-heart-failure-via-fatty-acid-oxidation
#7
Ekaterina Legchenko, Philippe Chouvarine, Paul Borchert, Angeles Fernandez-Gonzalez, Erin Snay, Martin Meier, Lavinia Maegel, S Alex Mitsialis, Eva A Rog-Zielinska, Stella Kourembanas, Danny Jonigk, Georg Hansmann
Right ventricular (RV) heart failure is the leading cause of death in pulmonary arterial hypertension (PAH). Peroxisome proliferator-activated receptor γ (PPARγ) acts as a vasoprotective metabolic regulator in smooth muscle and endothelial cells; however, its role in the heart is unclear. We report that deletion of PPARγ in cardiomyocytes leads to biventricular systolic dysfunction and intramyocellular lipid accumulation in mice. In the SU5416/hypoxia (SuHx) rat model, oral treatment with the PPARγ agonist pioglitazone completely reverses severe PAH and vascular remodeling and prevents RV failure...
April 25, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29690591/roles-of-pde1-in-pathological-cardiac-remodeling-and-dysfunction
#8
REVIEW
Si Chen, Walter E Knight, Chen Yan
Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways...
April 23, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29687617/noninvasive-assessment-of-autonomic-function-in-human-neonates-born-at-the-extremes-of-fetal-growth-spectrum
#9
Hasthi U Dissanayake, Rowena L McMullan, Adrienne Gordon, Ian D Caterson, David S Celermajer, Melinda Phang, Camille Raynes-Greenow, Michael R Skilton, Jaimie W Polson
Birth weight is associated with adult cardiovascular disease, such that those at both ends of the spectrum are at increased risk. This may be driven in part by modification to autonomic control, a mechanistic contributor to hypertension. However, birth weight is a relatively crude surrogate of fetal growth; and newborn body composition may more accurately identify the "at risk" infant. Accordingly, we sought to determine whether newborns with high or low body fat have altered autonomic control of vasomotor function and cardiac contractility...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29685688/critical-role-of-the-chymase-angiotensin-1-12-axis-in-modulating-cardiomyocyte-contractility
#10
Tiankai Li, Xiaowei Zhang, Heng-Jie Cheng, Zhi Zhang, Sarfaraz Ahmad, Jasmina Varagic, Weimin Li, Che Ping Cheng, Carlos M Ferrario
BACKGROUND: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for angiotensin II (Ang II) cardiac activity. The direct contractile effects of Ang-(1-12) in normal and heart failure (HF) remain to be demonstrated. We assessed the hypothesis that Ang-(1-12) may modulate [Ca2+ ]i regulation and alter cardiomyocyte contractility in normal and HF rats. METHODS AND RESULTS: We compared left ventricle (LV) myocyte contractile and calcium transient ([Ca2+ ]iT ) responses to angiotensin peptides in 16 SD rats with isoproterenol-induced HF and 16 age-matched controls...
April 20, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29620051/manipulation-free-cultures-of-human-ipsc-derived-cardiomyocytes-offer-a-novel-screening-method-for-cardiotoxicity
#11
Sheeja Rajasingh, Dona Greta Isai, Saheli Samanta, Zhi-Gang Zhou, Buddhadeb Dawn, William H Kinsey, Andras Czirok, Johnson Rajasingh
Induced pluripotent stem cell (iPSC)-based cardiac regenerative medicine requires the efficient generation, structural soundness and proper functioning of mature cardiomyocytes, derived from the patient's somatic cells. The most important functional property of cardiomyocytes is the ability to contract. Currently available methods routinely used to test and quantify cardiomyocyte function involve techniques that are labor-intensive, invasive, require sophisticated instruments or can adversely affect cell vitality...
April 5, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29618980/moderate-modulation-of-cardiac-pgc-1%C3%AE-expression-partially-affects-age-associated-transcriptional-remodeling-of-the-heart
#12
Natasha Whitehead, Jonathan F Gill, Marijke Brink, Christoph Handschin
Aging is associated with a decline in cardiac function due to a decreased myocardial reserve. This adverse cardiac remodeling comprises of a variety of changes, including a reduction in mitochondrial function and a decline in the expression of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a central regulator of mitochondrial biogenesis and metabolic adaptation in the myocardium. To study the etiological involvement of PGC-1α in cardiac aging, we used mouse models mimicking the modest down- and upregulation of this coactivator in the old and the exercised heart, respectively...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29616829/chronic-testosterone-administration-improves-cardiac-contractility-and-has-a-beneficial-effect-on-the-haemostatic-system-by-enhancing-fibrinolytic-activity-and-inducing-hypocoagulation-in-healthy-rats
#13
Naif M Alhawiti, Sultan A Alqahtani
This study investigated the effects of chronic supraphysiological dose of testosterone propionate administration cardiovascular function in rats from the perspective of haemostatic function including platelet functions, coagulation, and fibrinolysis. Testosterone significantly enhanced cardiac contractility by enhancing LVSP (10%), dp/dtmax (36.7%), dp/dtmin (14.6%) without altering heart rate, diastolic function, and serum lipid profile. While it has no effect on platelets count, thromboxane B2 levels, and platelet aggregation, testosterone significantly enhanced bleeding time and increased circulatory and thoracic aorta mRNA and protein levels of tPA (46...
April 4, 2018: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29611325/modulation-of-the-sympathetic-nervous-system-in-youngsters-by-vitamin-d-supplementation
#14
Rune Tønnesen, Peter Schwarz, Peter Hovind, Lars Thorbjørn Jensen
The level of circulating vitamin D is known to be associated with the ejection fraction in heart failure patients and studies in rats have shown that vitamin D depletion leads to increased levels of circulating norepinephrine and decreased atrial contractility. We elucidated the effects of vitamin D supplementation on the autonomous nervous system in healthy youngsters. Thirty healthy subjects aged 18-25 years were recruited based on their serum 25-hydroxyvitamin D (25[OH]D): 15 vitamin D insufficient (25[OH]D < 50 nmol/L) and 15 vitamin D sufficient (25[OH]D > 80 nmol/L) subjects...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29599964/syncytium-calcium-signaling-and-macrophage-function-in-the-heart
#15
REVIEW
Xin Zhou, Zhongguang Li, Zefan Wang, Eda Chen, Juan Wang, Frederic Chen, Odell Jones, Tao Tan, Shawn Chen, Hiroshi Takeshima, Joseph Bryant, Jianjie Ma, Xuehong Xu
Macrophages are traditionally viewed as a key component of the immunity defense system. Recent studies have identified resident macrophages in multiple organs including the heart, in which the cells perform their crucial role on tissue repair after myocardial infarction (MI). The cardiac-specific macrophages interdigitate with cardiomyocytes particularly at the atrioventricular node region. The integrative communication between macrophage and cardiomyocytes can modulate the contractile function of the heart...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29593122/inhibition-of-at1-receptors-by-losartan-affects-myocardial-slow-force-response-in-healthy-but-not-in-monocrotaline-treated-young-rats
#16
Oleg Lookin, Alexandr Balakin, Yuri Protsenko
The slow force response (SFR) of a cardiac muscle to a sudden stretch is thought to be important in the regulatory adaptation of myocardial contraction. Autocrine-paracrine regulation pathways which involve angiotensin II are participating in this mechanism. On the other hand, renin-angiotensin-aldosterone system (RAS) is altered in hypertrophic or failing myocardium. We compared the effects of sudden stretch to SFR as well as to twitch and Ca2+ transient characteristics in rat myocardium with monocrotaline-induced heart failure with those in normal rat myocardium without and with inhibition of angiotensin II type-1 (AT1) receptors...
March 2018: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29575758/a-selenoprotein-t-derived-peptide-protects-the-heart-against-ischemia-reperfusion-injury-through-inhibition-of-apoptosis-and-oxidative-stress
#17
Carmine Rocca, Loubna Boukhzar, Maria Concetta Granieri, Ifat Alsharif, Rosa Mazza, Benjamin Lefranc, Bruno Tota, Jérôme Leprince, Maria Carmela Cerra, Youssef Anouar, Tommaso Angelone
AIM: Selenoprotein T (SelT or SELENOT) is a novel thioredoxin-like enzyme whose genetic ablation in mice results in early embryonic lethality. SelT exerts an essential cytoprotective action during development and after injury through its redox-active catalytic site. The present study aims to determine the expression and regulation of SelT in the mammalian heart in normal and pathological conditions, and to evaluate the cardioprotective effect of a SelT-derived peptide, SelT43-52(PSELT) encompassing the redox motif which is key to its function, against ischemia/reperfusion(I/R) injury...
March 25, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29566368/the-trend-of-%C3%AE-3-adrenergic-receptor-in-the-development-of-septic-myocardial-depression-a-lipopolysaccharide-induced-rat-septic-shock-model
#18
Ni Yang, Xiao-Lu Shi, Bing-Lun Zhang, Jian Rong, Tie-Ning Zhang, Wei Xu, Chun-Feng Liu
Septic shock with low cardiac output is very common in children. However, the mechanism underlying myocardial depression is unclear. The role of β3-AR in the development of myocardial depression in sepsis is unknown. In the present study, we generated an adolescent rat model of hypodynamic septic shock induced by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS to mimic myocardial depression in sepsis, which was confirmed via an in vivo left ventricular hemodynamic study, and measurements of contractility and the Ca2+ transient in isolated adolescent and neonatal cardiomyocytes...
March 22, 2018: Cardiology
https://www.readbyqxmd.com/read/29544934/stress-induced-protein-s-glutathionylation-and-phosphorylation-crosstalk-in-cardiac-sarcomeric-proteins-impact-on-heart-function
#19
Nourdine Chakouri, Cyril Reboul, Doria Boulghobra, Adrien Kleindienst, Stéphane Nottin, Sandrine Gayrard, François Roubille, Stefan Matecki, Alain Lacampagne, Olivier Cazorla
BACKGROUND: The interplay between oxidative stress and other signaling pathways in the contractile machinery regulation during cardiac stress and its consequences on cardiac function remains poorly understood. We evaluated the effect of the crosstalk between β-adrenergic and redox signaling on post-translational modifications of sarcomeric regulatory proteins, Myosin Binding Protein-C (MyBP-C) and Troponin I (TnI). METHODS AND RESULTS: We mimicked in vitro high level of physiological cardiac stress by forcing rat hearts to produce high levels of oxidized glutathione...
May 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29544221/pim-1-kinase-phosphorylates-cardiac-troponin-i-and-regulates-cardiac-myofilament-function
#20
Ni Zhu, Bing Yi, Zhifu Guo, Guanxin Zhang, Shengdong Huang, Yongwen Qin, Xianxian Zhao, Jianxin Sun
BACKGROUND/AIMS: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI), a key component in regulating myofilament function in the heart. METHODS: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes...
March 10, 2018: Cellular Physiology and Biochemistry
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