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André M Travessa, L Menezes Falcão
Acute heart failure (AHF) contributes largely to the worldwide burden of heart failure (HF) and is associated with high mortality, poor prognosis and high rehospitalization rate. The pharmacologic therapy of AHF includes diuretics and vasodilators, which are a keystone when fluid overload and congestion are present. However, vasodilators are mainly focused on controlling symptoms, and drugs that also improve long-term mortality and morbidity seem to be in high demand. In this review, we summarize the existing evidence on mortality benefits of IV vasodilators in AHF...
February 23, 2018: European Journal of Internal Medicine
Shoichi Kageyama, Kojiro Nakamura, Bibo Ke, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a risk factor for early graft dysfunction and an obstacle to expanding donor pool in orthotopic liver transplantation (OLT). We have reported on the crucial role of macrophage Notch1 signaling in mouse warm hepatic IRI model. However, its clinical relevance or therapeutic potential remain unknown. Here, we used Serelaxin (SER), to verify Notch1 induction and putative hepatoprotective function in IR-stressed OLT. C57BL/6 mouse livers subjected to extended (18hr) cold storage were transplanted to syngeneic recipients...
February 21, 2018: American Journal of Transplantation
Maggie Lam, Simon G Royce, Chrishan S Samuel, Jane E Bourke
The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates it from these existing therapies. Relaxin has previously been reported to have cardioprotective effects in acute heart failure as well anti-fibrotic actions in several organs...
February 12, 2018: Pharmacology & Therapeutics
Patrick O Myers, Alice Bordessoule, Cécile Tissot
Serelaxin has been studied in trials in adults with acute heart failure, but not in children. We report the first compassionate use of serelaxin in an infant. A 6-month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane oxygenation following cardiac arrest unresponsive to medical treatment. Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator therapy. During the 48-hour infusion of serelaxin, we observed marked improvement in brain natriuretic peptide, left ventricular systolic function, and dilatation...
January 15, 2018: Cardiology in the Young
Marco Metra, Beth A Davison, Claudio Gimpelewicz, Valentina Carubelli, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Tsushung A Hua, Zoe Liu, Peter S Pang, Piotr Ponikowski, Thomas M Severin, Adriaan A Voors, Yi Wang, Gad Cotter, John R Teerlink
BACKGROUND: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response. METHODS AND RESULTS: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year)...
February 15, 2018: International Journal of Cardiology
Xue-Ping Wu, Hai-Jie Wang, Yong-Li Wang, Hao-Ran Shen, Yu-Zhen Tan
Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after inducion with TGF-β1 were examined...
October 4, 2017: Experimental Cell Research
Weijian Shao, Carla B Rosales, Camila Gonzalez, Minolfa C Prieto, L Gabriel Navar
Serelaxin is a novel recombinant human relaxin-2 that has been investigated for the treatment of acute heart failure. However, its effects on renal function, especially on the renal microcirculation remain incompletely characterized. Our immunoexpression studies localized RXFP1 receptors on vascular smooth muscle cells and endothelial cells of afferent arterioles and on principal cells of collecting ducts. Clearance experiments were performed in male and female normotensive rats and Ang II infused male rats...
October 4, 2017: American Journal of Physiology. Renal Physiology
Dong Wang, Yuhuan Luo, Komuraiah Myakala, David J Orlicky, Evgenia Dobrinskikh, Xiaoxin Wang, Moshe Levi
Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks...
August 29, 2017: Scientific Reports
Diana H Kim, Feng-Ju Chien, Howard J Eisen
PURPOSE OF REVIEW: This review aims to summarize the growing body of literature of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) with a focus on recent pharmacologics. RECENT FINDINGS: HFrEF continues to be more widely investigated than HFpEF. Ivabradine and combinatorial treatment with sacubitril and valsartan are promising newly approved therapies. Other experimental therapies have emerged, which include Serelaxin, Empagliflozin, Neuregulin, and Omecamtive mecarbil, among others...
August 24, 2017: Current Cardiology Reports
Claudio Gimpelewicz, Marco Metra, John G F Cleland, Peter Szecsödy, Chuan-Chuan Chang Wun, Leandro Boer-Martins, Gad Cotter, Beth A Davison, Gary Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter Pang, Piotr Ponikowski, Thomas Severin, Adrian A Voors, John R Teerlink
BACKGROUND: Acute heart failure (AHF) is a heterogeneous disorder, with most of the patients presenting with breathlessness along with varying degrees of peripheral edema. The presence of peripheral edema suggests that volume overload is the cause of decompensation leading to AHF, whereas breathlessness in the absence of edema may reflect a "vascular phenotype." This analysis investigated the characteristics, therapeutic response, and outcome of patients with AHF, with and without overt peripheral edema in the RELAX-AHF trial...
August 2017: American Heart Journal
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
No abstract text is available yet for this article.
July 27, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Jesus Sanchez-Mas, Antonio Lax, Mari C Asensio-Lopez, Miriam Lencina, Maria J Fernandez-Del Palacio, Angela Soriano-Filiu, Rudolf A de Boer, Domingo A Pascual-Figal
Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days...
December 2017: Journal of Cardiovascular Translational Research
Veronika Wetzl, Elisabeth Schinner, Frieder Kees, Lothar Faerber, Jens Schlossmann
Renal fibrosis is an important factor for end-stage renal failure. However, only few therapeutic options for its treatment are established. Zaprinast, a phosphodiesterase 5 inhibitor, and serelaxin, the recombinant form of the naturally occurring hormone relaxin, are differently acting modulators of cyclic guanosine monophosphate (cGMP) signaling. Both agents enhance cGMP availability in kidney tissue. These substances alone or in combination might interfere with the development of kidney fibrosis. Therefore, we compared the effects of combination therapy with the effects of monotherapy on renal fibrosis...
September 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
Robert G Bennett, Ronda L Simpson, Frederick G Hamel
AIM: To determine the effect of combined serelaxin and rosiglitazone treatment on established hepatic fibrosis. METHODS: Hepatic fibrosis was induced in mice by carbon tetrachloride administration for 6 wk, or vehicle alone (nonfibrotic mice). For the final 2 wk, mice were treated with rosiglitazone, serelaxin, or both rosiglitazone and serelaxin. Serum liver enzymes and relaxin levels were determined by standard methods. The degree of liver collagen content was determined by histology and immunohistochemistry...
June 14, 2017: World Journal of Gastroenterology: WJG
Filip Souček, Jan Novak
Heart failure (HF) is a complex clinical syndrome which is manifested by characteristic symptoms and objective signs of cardiac insufficiency. The incidence of HF, particularly its chronic form, is estimated 0.4-2 % in the central and western Europe, with an increase in higher age groups, affecting 10-20 % of the population aged over 80. With respect to its growing incidence and prevalence, novel modalities of pharmacological and non-pharmacological treatment are being developed in order to improve quality of life and survival of the affected patients...
December 0: Vnitr̆ní Lékar̆ství
René Schiffner, Juliane Reiche, Martin Schmidt, Christian Jung, Sebastian Walther, Andrey Irintchev, Sabine J Bischoff
BACKGROUND: The influence of the recombinant form of human relaxin-2 (serelaxin) on pulmonary hemodynamics under physiologic conditions have not been the subject of studies in an animal model up until now. METHODS: We therefore utilised the large animal model sheep, convenient in its similar cardiovascular physiology, to investigate said influence. All animals underwent right heart catheterization, a safe and reliable invasive procedure for the assessment of pulmonary hemodynamics, and then received either 30μg/kg serelaxin (n = 11) or saline (n = 13)...
May 2, 2017: Clinical Hemorheology and Microcirculation
Peter S Pang, John R Teerlink, Leandro Boer-Martins, Claudio Gimpelewicz, Beth A Davison, Yi Wang, Adriaan A Voors, Thomas Severin, Piotr Ponikowski, Tsushung A Hua, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Gad Cotter, Marco Metra
BACKGROUND: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial. METHODS: This is a post hoc analysis of the RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo, both in addition to usual AHF therapy...
May 2017: American Heart Journal
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
May 1, 2017: Cardiovascular Research
John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Peter S Pang, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A Hua, Thomas Severin, Marco Metra
Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180...
June 2017: European Journal of Heart Failure
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No abstract text is available yet for this article.
April 11, 2017: Nature Biotechnology
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