Effects of reference compounds on impedance signals from stem cellderived human cardiomyocytes
|
|
|
- Stephany Jennings
- 6 years ago
- Views:
Transcription
1 Effects of reference compounds on impedance signals from stem cellderived human cardiomyocytes Herbert M. Himmel, Safety Pharmacology, Bayer Pharma AG, Wuppertal, Germany SPS Webinar Cardiac Safety Testing Models 20 NOV 2014 Page 1
2 Disclaimer The thoughts expressed here are those of the speaker and do not necessarily reflect those of the speakers employer Bayer HealthCare AG. Page 2
3 Agenda introduction stem cell-derived cardiomyocytes impedance assay: principle & examples summary & conclusion Page 3
4 Introduction (1) 1990s: market withdrawal and late stage failure of drugs due to sudden cardiac death associated with QT prolongation and herg K + channel block 2005: ICH guidelines S7B and E14 cardiac risk assessment using at the very least herg assay, animal QT assay, and human thorough QT study 2010s: limited ability to predict risk of cardiotoxicity at substantial costs Recent technological developments: human induced pluripotent stem (hips) cell-derived cardiomyocytes measurement of impedance signals ± field potentials improved prediction of cardiotoxicity and proarrhythmia? Revolution dawning in cardiotoxicity testing Nature Rev. Drug Discov. 2013; 12: Page 4
5 Introduction (2) compound failure due to cardiotoxicity ~25% electrophysiology ~75% Ca homeostasis mitochondria Nature Rev. Drug Discov. 2013; 12: [Ca 2+ ] i handling coordinated activity of ion channels electrical activity mechanical activity energy supply mitochondria How can impedance signals from hipsc-derived cardiomyocytes improve early safety assessment and prediction of drug-induced cardiotoxicity?? Page 5
6 Agenda introduction stem cell-derived cardiomyocytes impedance assay: principle & examples summary & conclusion Page 6
7 Stem cell-derived vs adult cardiomyocytes: phenotype similar, but different slow (ultra)structural maturation 25 µm cardiac markers striation pattern cell shape alignment cell shortening Kattman et al. (2011) J CV Trans Res 4:66 (icells ) adult human VM (failing heart) Harding et al. (2007) Pharmacol Ther 113:341 Kamakura et al. (2013) Circ. J. 77:1307 Page 7
![hesc-cm, hipsc-cm [healthy, LQT, HCM, DCM]](/docs-images/74/70209217/images/8-5.jpg "ion channels: I Na, I to, I Ca.")
8 Human SC-derived cardiomyocytes: partially immature gene expression pattern Ca 2+ handling & ion channel genes Synnergren et al. (2012) Physiol. Genomics 44:245 (hesc cell line SA002) 0- (UD), 3- and 7-weeks post-differentiation versus fetal/adult heart (FH/AH) Liang et al. (2013) Circulation 127:1677 adult LV, hesc-cm, hipsc-cm [healthy, LQT, HCM, DCM] ion channels: I Na, I to, I Ca.L, herg (I Kr ), KvLQT1 (I Ks ), I K1 Page 8
9 Agenda introduction stem cell-derived cardiomyocytes impedance assay: principle & examples summary & conclusion Page 9
10 SC-derived cardiomyocytes: impedance-based contraction monitoring (1) measurement principle: impedance signals 96-well plate-based systems rhythmic contractions of spontaneously beating cardiomyocytes short-/long-term ms s min hrs - d early assay for contractility? low-voltage signal current cell spreading impedance (cell index) cell shape impedance Himmel (2013) JPTM 68:97 Page 10
11 SC-derived cardiomyocytes: impedance-based contraction monitoring (2) CO 2 incubator ACEA xcelligence CardioECR Nanion CardioExcyte 96 Page 11
12 SC-derived cardiomyocytes: impedance-based contraction monitoring (3) Impedance signal analysis: amplitude duration rise/fall time beating rate irregularity Guo et al. (2011) Toxicol Sci 123:281 Page 12
13 Human ipsc cardiomyocytes: impedance-based arrhythmia detection E-4031 Guo et al. (2011) Toxicol Sci 123:281 (icells ) Himmel (2013) JPTM (icells ) impedance-based contractions: amplitude( ), rate /, arrhythmia guinea-pig ventricular myocytes and LA/RA: cell shortening force (+20%), rate (-25%) (Wettwer et al., 1991) Page 13
14 Human ipsc cardiomyocytes: impedance-based contraction monitoring (4) ATX-II verapamil Himmel (2013) JPTM (icells ) impedance-based contractions: amplitude ( ), rate, AUC guinea-pig/rat ventric. myocytes & pap. m.: cell shortening, force (Hoey et al., 1994; Isenberg & Ravens, 1984) impedance-based contractions: amplitude ( ), rate / dog VM, gp RA, human PM: cell shortening, rate, force (Harmer, 2012; Tanaka, 1996; Schwinger, 1990) Page 14
15 Human ipsc cardiomyocytes: impedance-based contraction monitoring (5) 0.36 µm human ipsc-cm 10.8 µm Jonsson et al. (2011) Assay DDT 9:589 impedance-based contractions (e.g. iso [ampl ( ), rate ], carb [ampl, rate ( )]) positive/negative ino-/chronotropic effects in multicellular cardiac tissue preparations due to negative amplitude-frequency relation in hipsc cardiomyocytes Peters et al. (2014) Cardiovasc. Toxicol. DOI /s impedance-based signals: proarrhythmia contractility Page 15
16 SC cardiomyocytes: impedance-based monitoring of delayed cardiotoxicity doxorubicin pentamidine Abassi et al. (2012) BJP 165:1424; mouse esc-cm Similar results: kinase inhibitor-mediated delayed cardiotoxicity + biomarkers (e.g. ctnt injury, cellular ATP) (Lamore et al. (2013) Toxicol. Sci. 135:402) Page 16
17 Agenda introduction stem cell-derived cardiomyocytes impedance assay: principle & examples summary & conclusion Page 17
18 Summary & Conclusion impedance assays in human SC-derived cardiomyocytes: strenghts, weaknesses, opportunities stem cell-derived cardiomyocytes impedance assay strength weakness opportunity accessible immature human disease reproducible heterogenous many techniques low anisotropy micropatterns simple throughput time scale imcompletely understood pacing field potentials biomarkers impedance assays in human SC-derived cardiomyocytes offer a lot of potential for early detection of drug-induced cardiotoxicity full leverage of this potential in combination with pacing and field potentials Page 18
19 Page 19 Thank you!
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes. on the ACEA xcelligence RTCA CardioECR
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the ACEA xcelligence RTCA CardioECR Application Note Version 2.1 / March 2018 Contents 1. Introduction 1 2. Assessment of pro-arrhythmic
Metrion Biosciences: the ion channel specialists
Metrion Biosciences: the ion channel specialists In depth profiling of human ipsc cardiomyocytes: From electrophysiology to phenotypic assays Saïd El-Haou, PhD 30 November 2017 www.metrionbiosciences.com
xcelligence RTCA Cardio Instrument Monitor Cardiomyocyte Beating in Real Time for Drug Discovery Research
xcelligence RTCA Cardio Instrument Monitor Cardiomyocyte Beating in Real Time for Drug Discovery Research xcelligence RTCA Cardio Instrument A new way to test for compound cardiotoxicity Cardiac liability
Multiparametric assessment of the effects of chemotherapeutic drugs on the (electro)physiology of Pluricyte Cardiomyocytes
Multiparametric assessment of the effects of chemotherapeutic drugs on the (electro)physiology of Pluricyte Cardiomyocytes Event Presenter Date Ncardia Workshop Tessa de Korte, MSc December 1, 2017 Page
Advances in Safety Pharmacology: Utilizing ipsc-derived cardiomyocytes in early stage safety pharmacology investigations. Blake Anson, PhD.
Advances in Safety Pharmacology: Utilizing ipsc-derived cardiomyocytes in early stage safety pharmacology investigations Blake Anson, PhD. Presentation Outline I. Safety Pharmacology and in-vitro models
Welcome to the Exhibitor Tutorial presented by
Welcome to the Exhibitor Tutorial presented by February 1, 217 1 Calcium Handling Assays with Human ipsc-derived Cell Types Coby Carlson, Ph.D. 7 February 217 Transformative Potential of ipsc Technology
Cardiomyocyte? March 14 th 2013
What Makes a Cardiomyocyte a Cardiomyocyte? Kyle Kolaja March 14 th 2013 What Makes a Cardiomyocyte a Cardiomyocyte? Shouldn t proliferate Should beat Should be fairly pure Should look like and express
InPulse: Development of an ipsc cardiomyocyte (ipsc-cm) platform to assess drug-induced contractility liabilities.
InPulse: Development of an ipsc cardiomyocyte (ipsc-cm) platform to assess drug-induced contractility liabilities. Sponsors: Arun Sridhar, Peter J. Clements, Brian Berridge, Drug induced contractility
mesc Derived Cardiomyocytes and the RTCA Cardio Instrument - The Perfect Match for Screening Cardiac Effects
mesc Derived Cardiomyocytes and the RTCA Cardio Instrument - The Perfect Match for Screening Cardiac Effects Dr. Kristina Tressat, Axiogenesis AG ELRIG Drug Discovery II 7-8 Sep 2011, Manchester Challange
MEA assays using human ipsc-derived cardiomyocytes; challenges and opportunities
MEA assays using human ipsc-derived cardiomyocytes; challenges and opportunities Event Presenter Date EMA Workshop 2017 Tessa de Korte, MSc 2017, October 5 Page 1 Ncardia at a glance Foundation Ncardia
Ncardia. Assessment of pro-arrhythmic effects in Pluricyte Cardiomyocytes. using the Axion BioSystems Maestro TM MEA system
Ncardia Stem cell experts Assessment of pro-arrhythmic effects in Pluricyte Cardiomyocytes using the Axion BioSystems Maestro TM MEA system Application note Version 2.0 Contents 1. Introduction 1 2. Assessment
Measuring Cardiac Activity:
icell Cardiomyocytes Application Protocol Measuring Cardiac Activity: Intracellular Calcium Flux Detection on the FLIPR Tetra System Introduction icell Cardiomyocytes are human cardiomyocytes that recapitulate
Measuring Cardiac Activity:
icell Cardiomyocytes 2 Application Protocol Measuring Cardiac Activity: Impedance Detection with xcelligence RTCA Cardio System Introduction icell Cardiomyocytes 2, human cardiomyocytes derived from induced
xcelligence System RTCA Cardio Instrument
xcelligence System Application Note No. 15 January 2013 xcelligence System RTCA Cardio Instrument Preclinical Cardiac Safety Assessment using Human ipsc Derived icell TM Cardiomyocytes Introduction Over
Preclinical Approaches to Assess Potential Small Molecule Kinase Inhibitor-Induced Cardiac Toxicity: Past, Present, and Future
Preclinical Approaches to Assess Potential Small Molecule Kinase Inhibitor-Induced Cardiac Toxicity: Past, Present, and Future Baichun Yang, MD, PhD, DABT FDA/CDER/OND/DCRP Opinions presented here are
We ve crossed the Chasm and climbed out of the Trough. Advances and advantages with ipsc-derived cell types in drug discovery.
We ve crossed the Chasm and climbed out of the Trough. Advances and advantages with ipsc-derived cell types in drug discovery. Blake Anson Ph.D. Oct 31, 2014 Technology Hype Cycle The Chasm The Trough
Differing responses of human stem cell-derived cardiomyocytes to arrhythmogenic drugs, determined using impedance measurements
Fundamental Toxicological Sciences (Fundam. Toxicol. Sci.) Vol.3, No.2, 47-53, 2016 47 Letter Differing responses of human stem cell-derived cardiomyocytes to arrhythmogenic drugs, determined using impedance
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the ACEA xcelligence RTCA CardioECR
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the ACEA xcelligence RTCA CardioECR Version 1.2 CONTENTS Getting started... 3 Technical support and training... 3 1. Introduction...
In Vitro Assessment to Replace the Clinical TQT Study: The Comprehensive In Vitro ProArrhythmia Assay (CiPA) Initiative
In Vitro Assessment to Replace the Clinical TQT Study: The Comprehensive In Vitro ProArrhythmia Assay (CiPA) Initiative Gary Gintant, AbbVie for the Comprehensive in Vitro ProArrhythmia Assay Group Hot
xcelligence Cardio Symposium 2014 Cardiotoxicity, QT Prolongation, and Arrhythmia Prediction Using icell Cardiomyocytes: Past, Present, and Future
xcelligence Cardio Symposium 2014 Cardiotoxicity, QT Prolongation, and Arrhythmia Prediction Using icell Cardiomyocytes: Past, Present, and Future Blake Anson Ph.D. Oct 18, 2014 Outline Proarrhythmia Testing
Perspectives on Evaluating and Managing Cardiovascular Safety Risk for Anticancer Drugs
Perspectives on Evaluating and Managing Cardiovascular Safety Risk for Anticancer Drugs DCTD/DTP/TPB Myrtle Davis, DVM, Ph.D. Chief, Toxicology and Pharmacology Branch Division of Cancer Treatment and
Differences in cardiac atrial and ventricular ion channels
Differences in cardiac atrial and ventricular ion channels Norbert Jost, PhD Department of Pharmacology & Pharmacotherapy, University of Szeged Division for Cardiovascular Pharmacology, Hungarian Academy
TdP Mechanisms and CiPA
TdP Mechanisms and CiPA Craig T. January, MD, PhD Division of Cardiovascular Medicine University of Wisconsin-Madison Cardiac Safety Research Consortium Hilton Washington DC December 6, 2016 Disclosures
Measuring Cardiac Activity:
icell Cardiomyocytes 2 Application Protocol Measuring Cardiac Activity: Impedance and Extracellular Field Potential Detection with CardioExcyte 96 System Introduction icell Cardiomyocytes 2, human cardiomyocytes
Mechanisms of Arrhythmogenesis: Focus on Long QT Syndrome (LQTS)
Mechanisms of Arrhythmogenesis: Focus on Long QT Syndrome (LQTS) Craig T. January, MD, PhD Division of Cardiovascular Medicine University of Wisconsin-Madison CSRC-HESI-FDA Rechanneling the Current Cardiac
Patient Susceptibilities in Preclinical Drug Safety Assessment
Patient Susceptibilities in Preclinical Drug Safety Assessment B. R. Berridge GlaxoSmithKline ILAR Roundtable October, 2017 Animal studies represent an apical preclinical modeling system in drug development
hipsc Cardiomyocytes: Validation Study Results
CENTER FOR DEVICES AND RADIOLOGICAL HEALTH OFFICE OF SCIENCE AND ENGINEERING LABORATORIES hipsc Cardiomyocytes: Validation Study Results Ksenia Blinova, PhD US Food and Drug Administration HESI-CSRC CiPA
microheart: A screening-ready, physiologically relevant human ipsc-derived cardiomyocyte platform.
: A screening-ready, physiologically relevant human ipsc-derived cardiomyocyte platform. Human induced Pluripotent Stem Cells (hipscs) enable assays with human, patient and organ/system-specific cells
Human induced pluripotent stem cell derived cardiomyocytes are a more relevant model for assessing drug-induced effects on mitochondrial function
Human induced pluripotent stem cell derived cardiomyocytes are a more relevant model for assessing drug-induced effects on mitochondrial function than H9C2 cells 16 January 2013 SLAS2013 Presentation Outline
TCP Transl Clin Pharmacol
TCP 2018;26(4):145-149 https://doi.org/10.12793/tcp.2018.26.4.145 Five years of the CiPA project (2013 2018) - what did we learn? Dong-Seok Yim* Department of Clinical Pharmacology and Therapeutics, Seoul
Safety Pharmacology Post Meeting Survey 2014
Q1 Please enter your personal information below. (If you want to be included in the 2014 Annual Meeting survey for a chance to win $200, this information is REQUIRED) Answered: 132 Skipped: 14 Name: Company:
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes. on the ACEA xcelligence RTCA CardioECR
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the ACEA xcelligence RTCA CardioECR User Guide Version 3.0 / March 2018 Contents 1. Introduction 2 2. Workflow 3 3. Important recommendations
An Impedance-Based Cellular Assay Using Human ipsc-derived Cardiomyocytes to Quantify Modulators of Cardiac Contractility
TOXICOLOGICAL SCIENCES, 142(2), 2014, 331 338 doi: 10.1093/toxsci/kfu186 Advance Access Publication Date: September 18, 2014 An Impedance-Based Cellular Assay Using Human ipsc-derived Cardiomyocytes to
HHS Public Access Author manuscript Circ Res. Author manuscript; available in PMC 2016 June 05.
Tissue and Animal Models of Sudden Cardiac Death Karim Sallam, MD *,1,2,3, Yingxin Li, PhD *,1,2,3, Philip T. Sager, MD 1,2, Steven R. Houser, PhD 4, and Joseph C. Wu, MD, PhD 1,2,3 1 Stanford Cardiovascular
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the Axion Maestro system
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the Axion Maestro system Version 1.0 CONTENTS Getting started... 3 Technical support and training... 3 1. Introduction... 4 2. Workflow...
Cardiac toxicity is a leading cause for drug attrition during. Molecular Cardiology
Molecular Cardiology Drug Screening Using a Library of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes Reveals Disease-Specific Patterns of Cardiotoxicity Ping Liang, MD, PhD*; Feng Lan, PhD*;
Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using ipsc Cells
457590JBXXXX10.1177/1087057112457590Jo urnal of Biomolecular ScreeningSirenko et al. 2012 Multiparameter In Vitro Assessment of Compound Effects on Cardiomyocyte Physiology Using ipsc Cells Journal of
Drug-induced cardiotoxicity: screening methods, regulatory context, commercial environment. Beremans Ltd / Insight Pharma Reports April 2008
Drug-induced cardiotoxicity: screening methods, regulatory context, commercial environment. Overview Beremans Ltd / Insight Pharma Reports April 2008 This report identifies and discusses methods, products
Ionchannels and channelopaties in the heart. Viktória Szőts
Ionchannels and channelopaties in the heart Viktória Szőts Action of membrane transport protein ATP-powered pump Ion chanels Transporters 10 1-10 3 ions/s 10 7-10 8 ions/s 10 2-10 4 ions/s Cardiac K +
Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development
Review Pluripotent stem cell models of cardiac disease and their implication for drug discovery and development Richard P. Davis 1,2*, Cathelijne W. van den Berg 1*, Simona Casini 1, Stefan R. Braam 1,3
Ion channel dysfunction and diseases of the heart
Basisvorlesung (BVO) Zelluläre Signaltransduktion- Krankheitsbilder Sommersemester 2015 902.384 PhD- Programm Molecular Signal Transduction Ion channel dysfunction and diseases of the heart H. Todt Dpt.
Induced Pluripotent Stem Cells: an Introduction Oren Caspi MD, PhD
Induced Pluripotent : an Introduction Oren Caspi MD, PhD The Sohnis laboratory for cardiac electrophysiology and regenerative medicine The Bruce Rappaport Faculty of Medicine, Technion - Israel Institute
Breakout #4 Phase 1 ECG:
Breakout #4 Phase 1 ECG: Potential Role of ECG under CiPA HESI CSRC CiPA Meeting Washington, DC - May 22, 2018 Jose Vicente, PhD Christine Garnett, PharmD Division of Cardiovascular and Renal Products
The action potential and the underlying ionic currents. Norbert Jost, PhD
The action potential and the underlying ionic currents Norbert Jost, PhD The propagation of the stimulation in the heart Sinus node Left atria His Bundle Conduction velocity in m/s Time to arrive from
Preclinical Cardiovascular Safety in Oncology: Do We Need Plumbers, Electricians, or Strength Trainers?
Preclinical Cardiovascular Safety in Oncology: Do We Need Plumbers, Electricians, or Strength Trainers? Gary Gintant, Ph.D. Dept. Integrative Pharmacology Integrated Sciences & Technology, AbbVie CSRC
Resident cardiac stem cells: how to find and use them
Resident cardiac stem cells: how to find and use them G. Hasenfuß Cardiology and Pneumology Heart Research Center Göttingen Georg-August-University Göttingen Definition: Stem cell Selfrenewal Stem cell
Blocking the Late Sodium Current
Non-classical Targets in Antiarrhythmic Therapy Blocking the Late Sodium Current Luiz Belardinelli, MD SVP, Cardiovascular Therapeutics Gilead Sciences, CA, USA Madrid June 28, 2011 Disclosures: Full time
Use of hipsc derived Cardiomyocytes for Cardiac Safety Evaluation
Use of hipsc derived Cardiomyocytes for Cardiac Safety Evaluation Liang Gu, MD, Msc Sr. Principal Scientist/Lab Head, ADRD Investigative Toxicology March 14 th, 2018 (SOT Workshop) DEPARTMENT OF HEALTH
A New Comprehensive Translational Paradigm Using Human ipsc-derived Cardiomyocytes for Safety Assessment of Drug-Induced Arrhythmias
A New Comprehensive Translational Paradigm Using Human ipsc-derived Cardiomyocytes for Safety Assessment of Drug-Induced Arrhythmias Armando Lagrutta Safety & Exploratory Pharmacology (SEP) Department
Highlights Basic and Translational Science
Highlights Basic and Translational Science Excitation-Contraction Coupling Frank R. Heinzel Medical University of Graz, Austria Acknowledgments Ole Kemi, University of Glasgow, UK Julia Sprenger, University
Preparing for Changing Cardiac Safety Regulations. Joy Olbertz, PharmD, PhD
Preparing for Changing Cardiac Safety Regulations Joy Olbertz, PharmD, PhD Questions? Do I still have to assess proarrhythmic potential of my compound in a Thorough QT (TQT) study? If I have a TQT to conduct,
From Bench to Practice: Cardiac Resynchronisation Therapy
From Bench to Practice: Cardiac Resynchronisation Therapy Molecular Changes in the Dyssynchronous Heart and Cardiac Resynchronisation Therapy Gordon F. Tomaselli, M.D. Professor of Medicine and Molecular
Pluricyte Cardiomyocytes. Axion BioSystems Maestro TM MEA system
Pluricyte Cardiomyocytes Axion BioSystems Maestro TM MEA system User Guide Version 3.0 / March 2018 Contents 1. Introduction 2 2. Workflow 3 3. Important recommendations 4 4. Equipment, Materials and
Pluricyte Cardiomyocytes
Pluricyte Cardiomyocytes Manual Version 2.1 / March 2018 Contents 1. Introduction 2 2. Equipment, Materials and Reagents 3 3. Methods 4 3.1 Coating of tissue culture plates 4 3.2 Thawing Pluricyte Cardiomyocytes
Comparison of Electrophysiological Data From Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes to Functional Preclinical Safety Assays
toxicological sciences 134(2), 412 426 2013 doi:10.1093/toxsci/kft113 Advance Access publication May 20, 2013 Comparison of Electrophysiological Data From Human-Induced Pluripotent Stem Cell Derived Cardiomyocytes
Is There a Genomic Basis to Acquired Channelopathic disease
Is There a Genomic Basis to Acquired Channelopathic disease Yaniv Bar-Cohen, M.D. Associate Professor of Pediatrics Division of Cardiology / Electrophysiology Children s Hospital Los Angeles Keck School
New ECG Biomarkers and their Potential Role in CiPA: Results and Implications
New ECG Biomarkers and their Potential Role in CiPA: Results and Implications HESI CSRC CiPA Meeting Washington, DC - May 21, 2018 Jose Vicente, PhD for the ECG Biomarker Working Group Division of Cardiovascular
Validation and Utility of Human ips-vascular Smooth Muscle Cells as an in vitro Vascular Model
Validation and Utility of Human ips-vascular Smooth Muscle Cells as an in vitro Vascular Model Caroline Archer, Senior Scientist (Drug Safety and Metabolism) 30 th November 2017 Background Drug-induced
Ionchannels and channelopaties in the heart
Ionchannels and channelopaties in the heart Csatorna müködés Több betegség Drugok kapcsolodása csat.hoz Sejtekbe ioncsat.expresszios módszerek, bemutatása Viktória Szőts Action of membrane transport protein
Successes and Evolving Challenges Posed by the Comprehensive In Vitro Proarrhythmia (CiPA) Initiative
Successes and Evolving Challenges Posed by the Comprehensive In Vitro Proarrhythmia (CiPA) Initiative Gary Gintant Dept. Integrative Pharmacology Integrated Sciences and Technology AbbVie For the CiPA
Collin County Community College
Collin County Community College BIOL. 2402 Anatomy & Physiology WEEK 5 The Heart 1 The Heart Beat and the EKG 2 1 The Heart Beat and the EKG P-wave = Atrial depolarization QRS-wave = Ventricular depolarization
BJP. British Journal of Pharmacology. MPaci 1,JHyttinen 1,BRodriguez 2 and S Severi 3
British Journal of Pharmacology RESEARCH PAPER Human induced pluripotent stem cell-derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block MPaci 1,JHyttinen
Progress in Biophysics and Molecular Biology
Progress in Biophysics and Molecular Biology 110 (2012) 166e177 Contents lists available at SciVerse ScienceDirect Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio
Performing Bioenergetic Analysis: Seahorse XFe96 Analyzer
icell Cardiomyocytes 2 Application Protocol Performing Bioenergetic Analysis: Seahorse XFe96 Analyzer Introduction The myocardium is the most metabolically active tissue in the body and is highly sensitive
Comparison of different proarrhythmia biomarkers in isolated rabbit hearts
Comparison of different proarrhythmia biomarkers in isolated rabbit hearts Summary of PhD Thesis Szabolcs Orosz, MSc Supervisor: Attila Farkas MD, PhD 2nd Dept. of Internal Medicine and Cardiology Centre
Modeling of Anatomy, Electrophysiology and Tension Development in the Human Heart
European Functional Cardiac Modeling Meeting Modeling of Anatomy, Electrophysiology and Tension Development in the Human Heart Dr.-Ing. Gunnar Seemann Overview Electrophysiology Tension development Anatomy
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the Axion BioSystems Maestro TM MEA system
Assessment of pro-arrhythmic effects using Pluricyte Cardiomyocytes on the Axion BioSystems Maestro TM MEA system Version 1.2 CONTENTS Getting started... 3 1. Introduction... 4 2. Workflow... 5 Important
Professor Eric Schulze-Bahr
No CoI. Professor Eric Schulze-Bahr Institute for Genetics of Heart Diseases Department of Cardiology and Angiology University Hospital Münster / Germany ICD therapy in asymptomatic or borderline LQTS
Effect of ryanodine on sinus node recovery time determined in vitro
Brazilian Ryanodine Journal and sinus of Medical node recovery and Biological time Research (1999) 32: 139-143 ISSN -879X Short Communication 139 Effect of ryanodine on sinus node recovery time determined
Human Pluripotent Stem Cell Cardiomyocyte Differentiation Kit (PSCCDK) Introduction Kit Components Cat. # # of vials Reagent Quantity Storage
Human Pluripotent Stem Cell Cardiomyocyte Differentiation Kit (PSCCDK) Catalog #5901 Introduction Human pluripotent stem cells (hpsc), including embryonic stem cells (ESC) and induced pluripotent stem
Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome
Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome Direct Evidence From Intracellular Recordings in the Intact Left Ventricular Wall Gan-Xin
Clinical endpoints for VT/VF suppression in Patients with ICDs: Living longer and feeling better
Clinical endpoints for VT/VF suppression in Patients with ICDs: Living longer and feeling better Preston M. Dunnmon, MD, MBA, FACP, FACC Division of Cardiovascular and Renal Products US Food and Drug Administration
Drug-induced arrhythmogenesis. Prediction and Mechanisms. Blanca Rodriguez and Computational Biology Group University of Oxford
Drug-induced arrhythmogenesis. Prediction and Mechanisms Blanca Rodriguez and Computational Biology Group University of Oxford Feb 3 rd, 29 Work done by Esther Pueyo, Lucia Romero, Alberto Corrias, Martin
Preventing Sudden Death in Young Athletes. Outline. Scope of the Problem. Causes of SCD in Young Athletes. Sudden death in the young athlete
Preventing Sudden Death in Young Athletes Ronn E. Tanel, MD Director, Pediatric Arrhythmia Service UCSF Children s Hospital Associate Professor of Pediatrics UCSF School of Medicine Outline Sudden death
The case for induced pluripotent stem cell-derived cardiomyocytes in pharmacological screening
BJP British Journal of Pharmacology DOI:10.1111/j.1476-5381.2012.02118.x www.brjpharmacol.org Themed Section: Regenerative Medicine and Pharmacology: A Look to the Future REVIEW The case for induced pluripotent
Tailored therapy in long QT syndrome
Tailored therapy in long QT syndrome Dominic Abrams St. Bartholomew s & Great Ormond Street Hospitals London, UK Disclosures None Tailored therapy in long QTS Which patients should have tailored therapy...?...
DECLARATION OF CONFLICT OF INTEREST
DECLARATION OF CONFLICT OF INTEREST Disclosures: Research grants & clinical trials (Gilead), honoraria & clinical trials (Berlin-Chemie/Menarini) Ranolazine in Heart Failure with Preserved Ejection Fraction
Patient Resources: Cardiac Channelopathies
Patient Resources: Cardiac Channelopathies Overview of Cardiac Channelopathies: CPVT, Long QT Syndrome and Brugada Syndrome Heart muscle cells contract because of movement of certain molecules (called
QT prolongation and drug-drug interactions. Filip Josephson M.D., Ph.D Clinical Assessor Swedish Medical Products Agency
QT prolongation and drug-drug interactions Filip Josephson M.D., Ph.D Clinical Assessor Swedish Medical Products Agency Disposition Introduction to QT prolongation Three relevant DDI scenarios Concluding
Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes
Zhu et al. Stem Cell Research & Therapy REVIEW Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes Renjun Zhu 1, Adriana Blazeski 1, Ellen Poon 2, Kevin
MEA Application Note: Primary Culture Cardiomyocytes from Chicken Embryo
MEA Application Note: Primary Culture Cardiomyocytes from Chicken Embryo Information in this document is subject to change without notice. No part of this document may be reproduced or transmitted without
Genetics of Sudden Cardiac Death. Geoffrey Pitt Ion Channel Research Unit Duke University. Disclosures: Grant funding from Medtronic.
Genetics of Sudden Cardiac Death Geoffrey Pitt Ion Channel Research Unit Duke University Disclosures: Grant funding from Medtronic Duke U N I V E R S I T Y Sudden Cardiac Death High incidence 50-100 per
SEMINAIRES IRIS. Sudden cardiac death in the adult. Gian Battista Chierchia. Heart Rhythm Management Center, UZ Brussel. 20% 25% Cancers !
Sudden cardiac death in the adult Gian Battista Chierchia. Heart Rhythm Management Center, UZ Brussel.! " # $ % Cancers National Vital Statistics Report, Vol 49 (11), Oct. 12, 2001. 20% 25% State-specific
AF#in#pa(ents#with#CAD# Is#dronedarone#a#good#choice?!
AF#in#pa(ents#with#CAD# Is#dronedarone#a#good#choice?! DRUG#PROPHYLAXIS#OF#AF:# FOCUS#ON#DRONEDARONE# Friday#16C10C2015# Harry%JGM%Crijns% Maastricht,%The%Netherlands% Disclosures Harry Crijns - research
The QT Interval Safety Endpoint for DR- TB trials. Kelly Dooley & Gary Maartens (Disclaimer: I know very little cardiac electrophysiology)
The QT Interval Safety Endpoint for DR- TB trials Kelly Dooley & Gary Maartens (Disclaimer: I know very little cardiac electrophysiology) The ECG tracing Physiology of a cardiac myocyte Flow of ions (Na
Can the Thorough QT Study Be Replaced? Norman Stockbridge Division of Cardiovascular and Renal Products FDA/CDER
Can the Thorough QT Study Be Replaced? Norman Stockbridge Division of Cardiovascular and Renal Products FDA/CDER Can the TQT study be replaced? Yes. Thank you. Any questions? Four genre of replacement
A MODEL OF GAP JUNCTION CONDUCTANCE AND VENTRICULAR TACHYARRHYTHMIA
A MODEL OF GAP JUNCTION CONDUCTANCE AND VENTRICULAR TACHYARRHYTHMIA X. D. Wu, Y. L. Shen, J. L. Bao, C. M. Cao, W. H. Xu, Q. Xia Department of Physiology, Zhejiang University School of Medicine, Hangzhou,
Development and Use of Quantitative Adverse Outcome Pathways: Lessons Learned from Application to Cardiotoxicity
Development and Use of Quantitative Adverse Outcome Pathways: Lessons Learned from Application to Cardiotoxicity Chemicals Concentration 0.1 µm 1 µm 10 µm 100 µm Weihsueh A. Chiu, PhD Department of Veterinary
Developing and Validating an In Silico Model for Proarrhythmia Risk Assessment Under the CiPA Initiative
Developing and Validating an In Silico Model for Proarrhythmia Risk Assessment Under the CiPA Initiative May 2018 Zhihua Li, PhD for the CiPA In Silico Working Group US Food and Drug Administration This
a lecture series by SWESEMJR
Electrolyte disturbances Hypokalaemia Decreased extracellular potassium increases excitability in the myocardial cells and consequently the effect of very severe hypokalaemia is ventricular arrhythmia.
CiPA, Pre-clinical Testing. Derek Leishman PhD DSP & ICH S7B
CiPA, Pre-clinical Testing Derek Leishman PhD DSP & ICH S7B Outline Introduction Scenarios Conclusion Expressing an opinion What is not covered? Analysis/critique of the components too little time to try
The Cardiovascular System
Chapter 18 Part A The Cardiovascular System 1/19/16 1 Annie Leibovitz/Contact Press Images Similarities of Cardiac and Skeletal Muscle RMP Ion concentration Deploarization Action Potential Repolarization
International Graduate Research Programme in Cardiovascular Science
1 International Graduate Research Programme in Cardiovascular Science This work has been supported by the European Community s Sixth Framework Programme under grant agreement n LSHM-CT-2005-01883 EUGeneHeart.
In Vivo Animal Models of Heart Disease. Why Animal Models of Disease? Timothy A Hacker, PhD Department of Medicine University of Wisconsin-Madison
In Vivo Animal Models of Heart Disease Timothy A Hacker, PhD Department of Medicine University of Wisconsin-Madison Why Animal Models of Disease? Heart Failure (HF) Leading cause of morbidity and mortality
Evolution of strategies to improve preclinical cardiac safety testing
OPINION Evolution of strategies to improve preclinical cardiac safety testing Gary Gintant, Philip T. Sager and Norman Stockbridge Abstract The early and efficient assessment of cardiac safety liabilities
Chapter 9. Learning Objectives. Learning Objectives 9/11/2012. Cardiac Arrhythmias. Define electrical therapy
Chapter 9 Cardiac Arrhythmias Learning Objectives Define electrical therapy Explain why electrical therapy is preferred initial therapy over drug administration for cardiac arrest and some arrhythmias
Stretching Cardiac Myocytes: A Finite Element Model of Cardiac Tissue
Megan McCain ES240 FEM Final Project December 19, 2006 Stretching Cardiac Myocytes: A Finite Element Model of Cardiac Tissue Cardiac myocytes are the cells that constitute the working muscle of the heart.
Cardiac arrhythmias. Janusz Witowski. Department of Pathophysiology Poznan University of Medical Sciences. J. Witowski
Cardiac arrhythmias Janusz Witowski Department of Pathophysiology Poznan University of Medical Sciences A 68-year old man presents to the emergency department late one evening complaining of increasing
Understanding the electrophysiological maturation of human adult cardiomyocytes
Understanding the Electrophysiological Maturation of Human Adult Cardiomyocytes Lessons from the heart to be used for differentiation of pluripotent stem cells into cardiomyocytes Nikki H.L. van den Heuvel
Atrial Fibrillation 10/2/2018. Depolarization & ECG. Atrial Fibrillation. Hemodynamic Consequences
Depolarization & ECG Atrial Fibrillation How to make ORDER out of CHAOS Julia Shih, VMD, DACVIM (Cardiology) October 27, 2018 Depolarization & ECG Depolarization & ECG Atrial Fibrillation Hemodynamic Consequences