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https://www.readbyqxmd.com/read/28806493/olaparib-a-clinically-used-poly-adp-ribose-polymerase-inhibitor-protects-against-oxidant-induced-cardiac-myocyte-death-in-vitro-and-improves-cardiac-contractility-during-early-phase-after-heart-transplantation-in-a-rat-model-in-vivo
#1
Sevil Korkmaz-Icöz, Bartosz Szczesny, Michela Marcatti, Shiliang Li, Mihály Ruppert, Felix Lasitschka, Sivakkanan Loganathan, Csaba Szabo, Gábor Szabó
BACKGROUND AND PURPOSE: Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) have recently been approved for human use for oncological indications. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effect of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in-vivo model of cardiac transplantation. EXPERIMENTAL APPROACH: H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen-peroxide (H2 O2 ) or with glucose-oxidase (GOx, which generates H2 O2 in the tissue culture medium)...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28805342/deletion-of-the-activating-nk-cell-receptor-nkg2d-accelerates-rejection-of-cardiac-allografts
#2
Cornelia Fabritius, Paul Viktor Ritschl, Thomas Resch, Mario Roth, Susanne Ebner, Julia Günther, Vanessa Mellitzer, Anh-Vu Nguyen, Johann Pratschke, Martina Sauter, Karin Klingel, Katja Kotsch
It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1(-/-) ). Although median survival was eight days for both recipient groups, we detected already at day 5 post-transplantation significantly greater intragraft frequencies of NKp46(+) NK cells in Klrk1(-/-) recipients than in wildtypes...
August 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28805266/hypothermic-pulsatile-preservation-of-kidneys-from-uncontrolled-deceased-donors-after-cardiac-arrest
#3
Xavier Matillon, Fabrice Danjou, Palmina Petruzzo, Olivier Thaunat, Thomas Rimmele, Claire Delsuc, Alexandre Faure, Maud Rabeyrin, Vannary Meas Yedid, William Hanf, Emmanuel Morelon, Lionel Badet, Ricardo Codas
Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 31.12.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with "in situ" cold perfusion or a normothermic regional perfusion...
August 14, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28805187/changes-in-patient-characteristics-following-cardiac-transplantation-the-montreal-heart-institute-experience
#4
Nicola Vistarini, Anthony Nguyen, Michel White, Normand Racine, Louis P Perrault, Anique Ducharme, Denis Bouchard, Philippe Demers, Michel Pellerin, Yoan Lamarche, Ismaïl El-Hamamsy, Geneviève Giraldeau, Guy Pelletier, Michel Carrier
BACKGROUND: Heart transplantation is no longer considered an experimental operation, but rather a standard treatment; nevertheless the context has changed substantially in recent years owing to donor shortage. The aim of this study was to review the heart transplant experience focusing on very long-term survival (≥ 20 years) and to compare the initial results with the current era. METHODS: From April 1983 through April 1995, 156 consecutive patients underwent heart transplantation...
August 3, 2017: Canadian Journal of Surgery. Journal Canadien de Chirurgie
https://www.readbyqxmd.com/read/28804814/factors-associated-with-cardiovascular-target-organ-damage-in-children-after-renal-transplantation
#5
Bianca Borchert-Mörlins, Daniela Thurn, Bernhard M W Schmidt, Anja K Büscher, Jun Oh, Tanja Kier, Elena Bauer, Sabrina Baig, Nele Kanzelmeyer, Markus J Kemper, Rainer Büscher, Anette Melk
BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study...
August 13, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28803602/short-and-long-term-therapeutic-efficacies-of-intravenous-transplantation-of-bone-marrow-stem-cells-on-cardiac-function-in-rats-with-acute-myocardial-infarction-a-meta-analysis-of-randomized-controlled-trials
#6
Can Jiang, Dong Zheng, Yun-Lu Feng, Jun Guo, Hai-Rui Li, Ai-Dong Zhang
Objective To investigate the short- and long-term therapeutic efficacies of intravenous trans- plantation of bone marrow stem cells (MSCs) in rats with experimental myocardial infarction by meta- analysis. Methods Randomized controlled trials were systematically searched from PubMed, Science Citation Index (SCI), Chinese journal full-text database (CJFD) up to December 2014. While the experimental groups (MSCs groups) were injected MSCs intravenously, the control groups were injected Delubecco's minimum essential medium (DMEM) or phosphate buffered saline (PBS)...
September 20, 2016: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28802997/prophylactic-use-of-an-intra-aortic-balloon-pump-in-a-high-risk-patient-with-peripartum-cardiomyopathy-requiring-cesarean-delivery
#7
R S Samalavicius, L Puodziukaite, I Radaviciute, I Norkiene, K Urbonas, I Misiuriene, V Janusauskas, A Zorinas, K Rucinskas, P Serpytis
The use of intra-aortic balloon counter-pulsation for circulatory support in pregnant women with cardiac failure is limited to several case reports. Few publications have addressed the use of intra-aortic balloon counter-pulsation during delivery. We report a case using prophylactic intra-aortic counter-pulsation during the management of a cesarean delivery in a patient with peripartum cardiomyopathy. A 28-year-old primigravid female at 37weeks of gestation was admitted with signs of worsening heart failure, and transthoracic echocardiography revealed a decreased left ventricular ejection fraction of 25%...
July 14, 2017: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/28802656/rethinking-papillary-muscle-resection-for-refractory-ventricular-tachycardia-in-the-lvad-era-a-case-report
#8
Zachary J Il'Giovine, Adam D DeVore, Chetan B Patel, Jason Koontz, Jacob Schroder
We report the case of a 57-year-old man with a history of ischemic cardiomyopathy who presented to the hospital with recurrent episodes of ventricular tachycardia refractory to antiarrhythmic medications. Mapping identified a deep premature ventricular contraction focus in the anterolateral papillary muscle, an area that has been previously identified as difficult to treat with radiofrequency catheter ablation. The hospital course was complicated by cardiogenic shock and VT-storm, and the patient ultimately underwent surgical resection of the anterolateral papillary muscle with left ventricular assist device placement as a successful bridge to cardiac transplantation...
July 12, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28801937/in-situ-split-liver-splitting-under-extra-corporeal-membrane-oxygenation-in-brain-dead-donor
#9
Assalino Michela, Pietro Majno, Christian Toso, Thierry Berney, Raphaël Giraud, Philipp Dutkowski, Axel Andres, Barbara Wildhaber, Laure Elkrief
Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in-situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs and four kidneys...
August 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28801074/rational-heart-transplant-from-hepatitis-c-donor-new-antiviral-weapons-conquer-the-trojan
#10
Robert L Gottlieb, Teena Sam, Suzanne Y Wada, James F Trotter, Sumeet K Asrani, Brian Lima, Susan M Joseph, Gonzalo Gonzalez-Stawinski, Shelley A Hall
BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely utilized for orthotopic heart transplantation (OHTx) due to post-transplant risks. New, highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. Upon daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir 400 mg / velpatasvir 100 mg (Epclusa) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy)...
August 8, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28800676/development-and-evaluation-of-heartbeat-a-machine-perfusion-heart-preservation-system
#11
Yongnan Li, Qingdong Zeng, Gang Liu, Junzhe Du, Bingren Gao, Wei Wang, Zhe Zheng, Shengshou Hu, Bingyang Ji
Static cold storage is accompanied with a partial safe ischemic interval for donor hearts. In this current study, a machine perfusion system was built to provide a better preservation for the donor heart and assessment for myocardial function. Chinese mini-swine (weight 30-35 kg, n = 16) were randomly divided into HTK, Celsior, and Heartbeat groups. All donor hearts were respectively preserved for 8 hours under static cold storage or machine perfusion. The perfusion solution is aimed to maintain its homeostasis based on monitoring the Heartbeat group...
August 11, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28799694/patient-with-a-total-artificial-heart-maintained-on-outpatient-dialysis-while-listed-for-combined-organ-transplant-a-single-center-experience
#12
Ramy M Hanna, Huma Hasnain, Mohammad Kamgar, Mina Hanna, Raffi Minasian, James Wilson
Advanced mechanical circulatory support is increasingly being used with more sophisticated devices that can deliver pulsatile rather than continuous flow. These devices are more portable as well, allowing patients to await cardiac transplantation in an outpatient setting. It is known that patients with renal failure are at increased risk for developing worsening acute kidney injury during implantation of a ventricular assist device (VAD) or more advanced modalities like a total artificial heart (TAH). Dealing with patients who have an implanted TAH who develop renal failure has been a challenge with the majority of such patients having to await a combined cardiac and renal transplant prior to transition to outpatient care...
August 11, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28797760/effect-of-left-ventricular-dysfunction-on-utilization-of-donor-hearts
#13
David Tryon, Nahidh W Hasaniya, Brice Jabo, Anees J Razzouk, Leonard L Bailey, David G Rabkin
BACKGROUND: In this study we investigated modern, non-utilization rates of potential cardiac donors with left ventricular dysfunction (LVD) to clarify this phenomenon's magnitude and the impact of recent studies suggesting these organs can be safely transplanted. METHODS: Using the United Network for Organ Sharing transplant database, we reviewed all donors evaluated between January 1, 2007 and June 30, 2014. Exclusion criteria included lack of consent and age <13 or >59 years...
July 19, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28797029/successful-use-of-equine-anti-thymocyte-globulin-atgam-for-fulminant-myocarditis-secondary-to-nivolumab-therapy
#14
Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill, Andrew Haydon
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality. METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28795995/toxic-myocarditis-caused-by-acetaminophen-in-a-multidrug-overdose
#15
Maxime Gosselin, Yann Dazé, Pascal Mireault, Marie Crahes
We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction...
August 9, 2017: American Journal of Forensic Medicine and Pathology
https://www.readbyqxmd.com/read/28795324/the-fgf23-klotho-axis-and-cardiac-tissue-doppler-imaging-in-pediatric-chronic-kidney-disease-a-prospective-cohort-study
#16
Ylva Tranæus Lindblad, Hannes Olauson, Georgios Vavilis, Ulf Hammar, Maria Herthelius, Jonas Axelsson, Peter Bárány
BACKGROUND: Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. METHODS: This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1...
August 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28791557/ren%C3%A3-favaloro-the-heart-surgeon
#17
Massimo Fioranelli, Maria Grazia Roccia, Miriam Rovesti, Francesca Satolli, Paola Petrelli, Claudio Feliciani, Torello Lotti
The story of René Favaloro is almost unknown to the general public. Christian Barnard, the cardiac surgeon who performed the world's first human-to-human heart transplant, is much more famous than him; still, nowadays many more lives are saved thanks to Favaloro's work rather than to heart transplants. This paper wants to pay tribute to a great doctor and an extraordinary man: René Favaloro.
August 8, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28790330/the-matrikine-acetylated-proline-glycine-proline-couples-vascular-inflammation-and-acute-cardiac-rejection
#18
Gregory A Payne, Jindong Li, Xin Xu, Patricia Jackson, Hongwei Qin, David M Pollock, J Michael Wells, Suzanne Oparil, Massoud Leesar, Rakesh P Patel, J Edwin Blalock, Amit Gaggar
The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790153/multiple-gene-variants-in-hypertrophic-cardiomyopathy-in-the-era-of-next-generation-sequencing
#19
Charlotte Burns, Richard D Bagnall, Lien Lam, Christopher Semsarian, Jodie Ingles
BACKGROUND: Multiple likely pathogenic/pathogenic (LP/P; ≥2) variants in patients with hypertrophic cardiomyopathy were described 10 years ago with a prevalence of 5%. We sought to re-examine the significance of multiple rare variants in patients with hypertrophic cardiomyopathy in the setting of comprehensive and targeted panels. METHODS AND RESULTS: Of 758 hypertrophic cardiomyopathy probands, we included 382 with ≥45 cardiomyopathy genes screened. There were 224 (59%) with ≥1 rare variant (allele frequency ≤0...
August 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28789911/discovery-of-tricyclic-dipyrrolopyridine-derivatives-as-novel-jak-inhibitors
#20
Hiroaki Yamagishi, Takayuki Inoue, Yutaka Nakajima, Jun Maeda, Hiroaki Tominaga, Hiroyuki Usuda, Takeshi Hondo, Ayako Moritomo, Fumihiro Nakamori, Misato Ito, Koji Nakamura, Hiroki Morio, Yasuyuki Higashi, Masamichi Inami, Shohei Shirakami
Janus kinases (JAKs) play a crucial role in cytokine mediated signal transduction. JAK inhibitors have emerged as effective immunomodulative agents for the prevention of transplant rejection. We previously reported that the tricyclic imidazo-pyrrolopyridinone 2 is a potent JAK inhibitor; however, it had poor oral absorption due to low membrane permeability. Here, we report the structural modification of compound 2 into the tricyclic dipyrrolopyridine 18a focusing on reduction of polar surface area (PSA), which exhibits potent in vitro activity, improved membrane permeability and good oral bioavailability...
July 27, 2017: Bioorganic & Medicinal Chemistry
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