who uses our systems for ecg studies in preclinical research and how

poster presented by Pieter-Jan Guns, Joeri Van Op den bosch, Els Weltens and Johan Lissens, Bio-Plus Safety Pharmacology, Vlasmeer, Belgium at the Safety Pharmacology Society meeting, Innsbruck, Austria, September 2011

the electro-mechanical window in anaesthetized guinea-pigs: a new marker for TdP risk screening

a negative electro-mechanical (E-M) window has been proposed as additional risk marker for TdP in a canine LQT1 model by van der Linde et al. The current work was aimed at explore the E-M window in anaesthetized guinea-pigs as potential screening marker for TdP risk in humans.

• E-M window = QLVPend - QT
• instrumented guinea-pigs
• ecgAUTO software
• Automated measurements of the electro-mechanical (E-M) window in anaesthetized guinea-pigs are feasible and reproducible

poster presented by Pieter-Jan Guns, Joeri Van Op den bosch, Els Weltens and Johan Lissens, Bio-Plus Safety Pharmacology, Vlasmeer, Belgium at the Safety Pharmacology Society meeting, Innsbruck, Austria, September 2011

accurate detection of ECG intervals in anaesthetized guinea-pigs: man versus machine

Accurate measurement of QT, PQ and QRS intervals in pre-clinical cardiovascular safety testing. The aim of this study was to compare the outcome of manual versus automated ECG analysis on efficiency and accuracy in anaesthetized guinea-pigs.

• automated analysis of individual complexes
• shape recognition algorithm
• user-defined ecg waveform library
• Female SPF Dunkin Hartley guinea-pigs
• assessment of left ventricular pressure (LVP)

Automated detection leads to accurate, reproducible and time-efficient analysis of ecg signals in anaesthetized guinea-pigs

poster presented by Pfizer, Global Safety Pharmacology and Pharma Therapeutics Biostatistics, Groton, CT, USA at the Safety Pharmacology Society meeting, Boston, MA, September 2010

the use of alternate QRS measurement methods to improve detection of propafenone-induced QRS prolongation

alternate methods of QRS interval measurement using propafenone, a compound that increases QRS duration

• beagle dogs
• measurement (prolongation) of the QRS interval
• safety pharmacology cardiovascular model

poster presented by Amgen, Department of Investigative Toxicology, Thousand Oaks, CA, USA at the Safety Pharmacology Society meeting, Boston, MA, September 2010

comprehensive arrhythmia analysis in telemetered non-human primates

determination of the normal frequency of arrhythmias in a colony of telemetered cynomolgus monkeys

• ecg waveform analysis
• PR interval analysis
• automated ecg analysis software can be leveraged to streamline detection
• quantification of arrhythmia incidence in telemetry colony is consistent with best practice recommendations

Cécile Fligny,* Yves Fromes,† Philippe Bonnin,§ Michèle Darmon,‡ Elisa Bayard,* Jean-Marie Launay,|| Francine Côté,* Jacques Mallet,*,1 and Guilan Vodjdani*,1, The FASEB Journal, Vol. 22 July 2008, *Unité Mixte de Recherche 7091 Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégénératifs (LGN), †Institut de Myologie, U582 Institut National de la Santé et de la Recherche Médicale, and ‡Unité Mixte de Recherche 677 Institut National de la Santé et de la Recherche Médicale/ Université Pierre et Marie Curie, Laboratoire de Neuropsychopharmacologie, Hôpital de la Pitié-Salpêtrière, Paris, France; and § Centre de Recherche Cardiovasculaire, Physiologic Explorations Fonctionnelles, U689 Institut National de la Santé et de la Recherche Médicale, Université Denis Diderot, and ||Service de Biochimie, Hôpital Lariboisière, APHP, Paris, France

serotonin influences cardiac function in adult offspring

cardiac function, through the plasma 5-HT concentration, is influenced by the maternal serotonergic status

• maternal effect
• heart failure animal model
• dilated cardiomyopathy
• ecgTUNNEL restraining device for small rodents
• emkaPACK external telemetry

poster presented by AstraZeneca, Global Safety Assessment, Alderley Park, Macclesfield, United Kingdom at the Society of Toxicology meeting, Salt Lake City, UT, March 2010

ecg recording methods in dog toxicology studies: what is the real benefit of external telemetry?

The availability of external telemetry using jacketed animals offers an interesting alternative that has been assessed in Tox studies for more than five years now. This review presents a comparison of historical data obtained using three different methods. Comparison of:

• standard snapshot recordings
• external telemetry (emka TECHNOLOGIES)
• standard invasive telemetry

Haisong Ju, Xuejun Wu, Robert Coatney, Jason Payseur, Lynne King, Jon Renninger, Dennis Murphy - poster presented by GlaxoSmithKline, UK, at the Society of Safety Pharmacology meeting, Madison, WI, USA, september 2008

an improved method for ecg recording in conscious dogs and monkeys : pericardial lead placement

study performed on dogs and monkeys

• comparison of ecg quality betwen pericardial lead placement method and standard subcutaneous ecg electrodes placement
• arrhythmias detections
• representative ecg waveforms from dog and non human primate using pericardial or subcutaneous electrodes placement

Haisong Ju, Xuejun Wu, Jason Payseur, Jon Renninger, Dennis Murphy - poster presented by GlaxoSmithKline, UK, at the Society of Safety Pharmacology meeting, Madison, WI, USA, september 2008

evaluation of test article-related ventricular premature complexes in conscious telemetered dogs

study performed on implanted beagle dogs

• ventricular arrhythmias detection using two methods:
• periodic analysis: visual inspection of selected timepoints
• (continuous analysis: ventricular premature complexes (VPCs) were quantified by analyzing all recorded ecg waveforms beat by beat for approximately 26 hours assisted by validated ecgAUTO computer software

Y. Panyasing1,², A. Kijtawornrat¹, C. Del Rio¹, L. Snedden¹, T. Mongkolmaneepol¹, J. Schmidt¹, T. Brown¹, R. Hamlin^1,2 1: QTest Labs, LLC, Columbus, OH 2: The Ohio State University, Columbus, OH, USA, - poster presented at the Society of Safety Pharmacology meeting, Madison, WI, USA, september 2008

analysis of dynamic restitution of ecg parameters in the rabbit Langendorff heart exposed to drugs that lengthen or abbreviate QT

study performed on ten anesthetized male rabbits

• relationship betwen escalating concentrations of dofetilide or pinacidil perfused on hearts and recorded parameters as QT
• screen captures of recordings made on an EMKA IOX Data Acquisition Unit.

Circulation, P. Kirchhof, L. Fabritz, M. Zwiener, H. Witt, M. Schäfers, S. Zellerhoff, M. Paul, T. Athai, K-H. Hiller, H. A. Baba, G. Breithardt, P. Ruiz, T. Wichter, B. Levkau, Hospital of the University of Muenster, Germany, July 2006

age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice

study performed on heterozygous plakoglobin-deficient mice to demonstrate that reduced desmosomal protein expression causes ARVC and this phenotype is accelerated by endurance training.

Journal of Pharmacological and Toxicological Methods, E. R. Nolan, M. R. Feng, J. R. Koup, J. Liu, D. Turluck, Y. Zhang, J. B. Paulissen, N. B. Olivier, T. Miller, M. B. Bailie, Pfizer Global Research and Development, Ann Arbor, MI, USA and Michigan State University College of Veterinary Medicine, East Lansing, MI, USA, February 2005

a novel predictive pharmacokinetic/ pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node-ablated, His bundle-paced dog

study performed on three male beagle dogs to evaluate the sensitivity of the conscious chronic atrioventricular node ablated,, His bundle-paced Dog for defining drug induced cardiacrepolarization prolongation - use of the EMKA system to analyze raw ecg data.

del Rio CL^1,2, Snedden L¹, Ueyama Y², Panyasing Y^1,2, Zwijnenberg R³, Kijtawornrat A^1,2, Hamlin RL^1,2, Muir WW^1,2
1: QTest Labs, 2: The Ohio State University - Columbus, OH (USA) and 3: Fort Dodge Animal Health - Princeton, NJ (USA) - poster presented at the Society of Safety Pharmacology meeting, Madison, WI, USA, september 2008

concentration-dependent changes in ecg-derived indices of repolarization triggered by Isoflurane : a study in telemetered beagle dogs

study performed on thirteen healthy beagle dogs

• evaluation of the independent ecg effects/liability of isoflurane anesthesia (ISO) in vivo
• screen captures of ecg signals analyzed by ecgAUTO.

Autonomic Neuroscience: Basic and Clinical, E. R. Nolan, M. B. Bailie , N.B. Olivier, Michigan State University, East Lansing, MI (USA), 2008

effect of autonomic blockade on ventricular repolarization shortening : response to behavioral stimulus in paced dogs

study performed on six male beagle dogs

• determine that parasympathetic withdrawal is the primary factor responsible in the facilitation of rate-independent repolarization shortening, following an excitatory stimulus in dogs
• graphs of RT Interval.

The FASEB Journal, J-C. Peter, J. Tugler, P. Eftekhari, D. Maurice, J. Hoebeke, J-C. Roegel, CNRS, IBMC, Strasbourg and Forenap Therapeutic Discovery, Strasbourg, France, 2005

effects on heart rate of an anti-M2 acetylcholine receptor immune response in mice

The study investigate the in vivo consequences on heart rate of the autoantibodie in vitro modulating the M2 acetylcholine receptor (M2ACh-R)s in mice.

Comparative Medicine, K. Nahas, P. Baneux, D. Detweiler, American Association for Laboratory Animal Science, USA, June 2002

electrocardiographic monitoring in the Göttingen minipig

The purpose of the study is to determine conditions for ecg monitoring in the Göttingen minipig in view of its use as a second non-rodent species in toxicology studies.

Haisong Ju, Xuejun Wu, Robert Coatney, Jason Payseur, Lynne King, Jon Renninger, Dennis Murphy GlaxoSmithKline, USA - poster presented at the Society of Safety Pharmacology meeting, Madison, WI, USA, september 2008

evaluation of test article-related ventricular premature complexes in conscious telemetered dogs

study performed on beagle dogs

• demonstrate the importance of a continuous analysis of ecg (with the assistance of emka ecgAUTO software), for detecting a test article-related ventricular arrhytmia in conscious telemetered dogs
• screen captures of ecgAUTO and graphs of VPCs data.

Environ Health Perspect, A. K. Farraj, N. Haykal-Coates,D. W. Winsett, M. S. Hazari, A. P. C., W. H. Rowan III, A. D. Ledbetter, W. E. Cascio, D. L. Costa, U.S. Environmental Protection Agency, Research Triangle Park, NC; University of North Carolina at Chapel Hill, Chapel Hill, NC; ITT Corporation, Advanced Engineering and Sciences, Alexandria, Virginia; Brody School of Medicine, East Carolina University, Greenville, NC, USA, 2008

increased non-conducted P-wave arrhythmias after a single oil fly ash inhalation exposure in hypertensive rats

study performed on male Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats to determine if SH rats are more susceptible to the development of PM-induced arrhythmia, altered ecg morphology, and reduced HRV than are WKY rats, a related strain with normal blood pressure.

Molecular and Cellular Biology, M. Membrez, E. Hummler, F. Beermann, J-A. Haefliger, R. Savioz, T. Pedrazzini, B. Thorens, University of Lausanne, Lausanne, Switzerland, June 2006

GLUT8 is dispensable for embryonic development but influences hippocampal neurogenenis and heart function

study performed on mice to show what relatively mild phenotypic alterations are led by inactivation of the glut8 gene. Analysis of electrocardiograms (by using the IOX data acquisition software and the ecgAUTO analysis software) on mice with suppressed GLUT8 expression r suggest a possible involvement of GLUT8 in the control of atrial contraction.

Laboratory Animals, P. Hess, M. Rey, D. Wanner, B. Steiner, M. Clozel, Actelion Pharmaceuticals Ltd, Switzerland, January 2007

measurements of blood pressure and electrocardiogram in conscious freely moving guineapigs a model for screening QT interval prolongation effects

study performed on male Dunkin Hartley guineapigs to assess whether conscious freely moving guineapigs can be used to predict QT prolongation in vivo, using telemetry system implantation.

Journal of Biological Chemistry, J-C. Peter, G. Wallukat, J. Tugler, D. Maurice, J-C. Roegel, J-P. Briand, J. Hoebeke, CNRS, Strasbourg, France, October 2004

modulation of the M2 Muscarinic Acetylcholine Receptor Activity with Monoclonal Anti-M2 Receptor Antibody Fragments

study performed on twelve mice to characterize a polypeptide with a specific inverse agonist activity on the M2 muscarinic receptor.

European Journal of Physiology, H. Mongue-Din, A. Salmon, M. Y. Fiszman, Y. Fromes, Institut de Myologie-INSERM U582, Groupe Hospitalier Pitié-Salpêtrière, France, January 2007

non-invasive restrained ecg recording in conscious small rodents: a new tool for cardiac electrical activity investigation

study performed on Syrian hamsters and several strains of mice

• comparison of a restrained ecg monitoring method and ecg monitoring using telemetry to obtain the best results on small animal models
• photograph of the six-lead restrained ecg monitoring system, ecgTUNNEL
• comparisons of ecg strip obtained with the ecgTUNNEL system and with telemetric system.

Hypertension, Q. Wang, A. A. Domenighetti, T. Pedrazzini, M. Burnier, University Hospital, Lausanne, Switzerland, June 2005

potassium supplementation reduces cardiac and renal hypertrophy independent of blood pressure in DOCA/salt mice

study performed on mice to determine if correcting hypokalemia would prevent the DOCA/salt-induced cardiac hypertrophy and ecg changes in normotensive gene and hypertensive gene mice.

Pacing and Clinical Electrophysiology, R. Sanders, M. Bailie, N. Bari Olivier, College of Veterinary Medicine, Michigan State University, MI, USA, November 2004

stability of ventricular repolarization in conscious dogs with chronic atrioventricular dissociation and His-bundle pacing

study performed on a conscious canine model of atrioventricular (AV) dissociation and His-bundle pacing

• description of the adaptation to a conscious model,
• evaluation of the stability of the model over 6 weeks of study
• preliminary assessment of the effects of programmed daily pacing rate on the QT-HR relationship
• echocardiographic evaluation of gross cardiac structural remodeling.

Circulation, A. Ouvrard-Pascaud, Y. Sainte-Marie, J-P. Bénitah, R. Perrier, C. Soukaseum, A. Nguyen Dinh Cat, A. Royer, K. Le Quang, F. Charpentier, S. Demolombe, F. Mechta-Grigoriou, A. T. Beggah, P. Maison-Blanche, M-E. Oblin, C. Delcayre, G. I. Fishman, N. Farman, B. Escoubet, F. Jaisser; INSERM U533, Medical School, Nantes, France, 2005

conditional mineralocorticoid receptor expression in the heart leads to life-threatening arrhythmias

Study performed on transgenic mouse model with conditional cardiac-specific overexpression of the human MR

• Specifically assess the role of the mineralocorticoid receptor (MR) in the heart, in the absence of changes in aldosteronemia.

Circulation, Anne Royer, PhD*; Toon A.B. van Veen, PhD*; Sabrina Le Bouter, PhD; Celine Marionneau, MSc; Violaine Griol-Charhbili, MSc; Anne-Laure Leoni, DVM; Marja Steenman, PhD; Harold V.M. van Rijen, PhD; Sophie Demolombe, PhD; Catharine A. Goddard, PhD; Christine Richer, PharmD, PhD; Brigitte Escoubet, MD, PhD; Therese Jarry-Guichard, PhD; William H. Colledge, PhD; Daniel Gros, PhD; Jacques M.T. de Bakker, PhD; Andrew A. Grace, PhD, FRCP; Denis Escande, MD, PhD; Flavien Charpentier, PhD, 2005

Mouse Model of SCN5A-Linked Hereditary Lenègre's Disease - age-related conduction slowing and myocardial fibrosis

study performed on Scn5a^+/- mouse model

Exp Physiol , Thireau J, Zhang BL, Poisson D, Babuty D. Laboratory of Cardiac and Vascular Cell Physiology (CNRS Unit "UMR 6542") , François-Rabelais University, Tours, France, 2007.

heart rate variability in mice: a theoretical and practical guide

The authors review the field of heart rate variability analysis and also attempt to establish a standardized protocol for the assessment of the autonomic neural regulation of heart rate in mice. This is necessary because currently, the multitudes of techniques used and subtle differences in methodology impede the comparison and clear interpretation of results.