2007年08月24日
A-5 Chikara Abe
【演題名】 完全埋め込み型マイクロインフュージョンポンプ「iPRECIO」の応用例
Applications of the infusion pump “iPRECIO” in conscious rats.
安部 力
岐阜大学 大学院医学系研究科 生理学分野
Chikara Abe
Department of Physiology, Graduate School of Medicine
Gifu University, 501-1194 Gifu, Japan
iPRECIOは，動物実験における新しいタイプのインフュージョンポンプである。iPRECIOはポンプ自体にプログラム可能な，完全埋め込み型マイクロインフュージョンポンプとして開発された。主な特徴としては，①完全埋め込み型であること，②プログラムにより投薬スピードを変化させることができること，③薬剤の再注入ができることにより長期の実験が可能であること，が挙げられる。この機能により，より正確な実験結果を提供することが可能となる。今回の発表では，意識下のラットを用いて，アンギオテンシンIIによる動脈血圧の変化を例に挙げて，iPRECIOの特徴と応用例を紹介する。
The iPRECIO is a novel type of the totally implanted and programmable micro-infusion pump for small animals. The major characteristics of iPRECIO are 1) totally implantable, 2) variable of the drug delivery speed，3) refillable during experiment. These functions which the conventional infusion pump system does not have will provide more precise data. In this presentation, we will introduce the some characteristics and applications of the iPRECIO from the aspect of the relationship between the arterial pressure and angiotensin II in conscious rats
✽ 講演時間変更のお知らせ:
8月24日 14:00 - 14:40の日程でご発表頂きます。(A-1 Dr.Jonny Roughanの講演中止に伴い、予定時間を変更致しました。8/21)
最新のタイムテーブルは、こちらからご確認下さい。
投稿者 prime-watanabe : 16:40
A-4 Tonya Coulthard M.Sc
【演題名】 Vevo 770® High-Resolution Ultrasound Imaging System for In Vivo Research
Tonya Coulthard
Molecular Applications Specialist
VisualSonics Inc.
The Vevo 770 is a high-resolution ultrasound system designed specifically for the imaging of small laboratory animals, such as mice and rats.
Ultrasound is a non-invasive imaging modality which provides anatomical, as well as hemodynamic information; and with the introduction of our MicroMarker Contrast Agents the Vevo 770 also provides molecular information as well.
This presentation will overview the Vevo 770 system, and images will be shown from a wide array of applications including developmental biology and tumor imaging, with the majority of time being spent on cardiovascular imaging. An entire section of the presentation will be reserved for the introduction of the MicroMarker Contrast Agents, showing representative images from the three product offerings.
投稿者 prime-watanabe : 16:00
A-3 Michiel Helmes, Ph.D.
【演題名】Research tools for cellular physiology: measuring force and fluorescence in single cells.
細胞生理学のための研究道具 ：単一細胞における力と蛍光の測定
Michiel Helmes
ION Optix Europe
The ability to measure calcium and dimension changes in live, individual cells has greatly helped to understand the physiology of mechanically active cells such as cardiac myocytes. Ionoptix has been instrumental in the growth of this research area by developing integrated systems for fluorescence and contractility measurements. Here Ionoptix presents an emerging new technique that allows to measure and control the force produced by individual myocytes, opening up a new area in single cell physiology research.
投稿者 prime-tazaki : 15:20
Tonya Coulthard, M.Sc.
Tonya Coulthard, M.Sc.
Molecular Applications Specialist
VisualSonics Inc.
= Experience ===============
2006 - present
Molecular Applications Specialist
Visual Sonics Inc. , Toronto, ON, CA
2002
Research Assistant
Canadian Science Centre for Human and Animal Health
Winnipeg, MB, CA
= Publications ===============
Churg A, Tai H, Coulthard T, Wang R, Wright JL. Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Am J Respir Crit Care Med. 2006. Dec 15; 174(12):1327-34.
= Education ===============
2003-2005 M.Sc Experimental Medicine
University of British Columbia, Vancouver, BC, CA
1998-2003 B.Sc Honors Biochemistry, co-op
University of Waterloo, Waterloo, ON, CA
【発表日程】 8月24日(金) A-4 Advanced Technologies Session アブストラクト
投稿者 prime-tazaki : 15:00
A-2 Hironobu Morita, Ph.D.
【演題名】 Long-term gravity load induces plastic alteration in vestibulo-cardiovascular reflex in conscious rats.
Hironobu Morita, Chikara Abe, Kunihiko Tanaka
Department of Physiology, Graduate School of Medicine
Gifu University, 501-1194 Gifu, Japan
Recently, we have demonstrated that the vestibular system has a major role in controlling arterial pressure (AP) during gravitational change. The vestibular system is known to be highly plastic, thus it is possible that exposure to an altered gravitational environment produces an adaptation in the vestibulo-cardiovascular reflex. To test this hypothesis, the AP response to gravitational change was examined in 2 groups of rats, the 3-G group and 1-G group, in which rats were kept under 3 G or 1 G environment for 2 weeks, respectively. To further examine the central activation, glutamate concentration in the hypothalamus was measured using enzyme-based glutamate biosensor probe (Pinnacle Technology, Lawrence, KS). Gravitational change was produced by parabolic flight, which consisted of three phases, “pull-up”, during which the G load gradually increased to 2 G, a 20 s “push-over” into microgravity, and “pull-out”, during which the G load increased to 1.8. Subsequently, G returned to 1. In the 1-G group, the AP increased by 11.9 ± 1.2 mmHg during pull-up hypergravity period. The AP response was significantly attenuated in the 3-G group (4.0 ± 0.8 mmHg). During push-over microgravity period, the AP decreased from the peak level of pull-up period and recovered to the pre-parabola control level (-1.8 ± 2.4 mmHg). In rats of 3-G group, the AP was not altered by push-over microgravity. These AP responses were associated with a significant increase in glutamate concentration in the hypothalamus (4.4 ± 0.7%). The glutamate response was also significantly attenuated in the 3-G group compared with the 1-G group. These results indicate that an altered gravitational environment induces plastic alterations in the vestibulo-cardiovascular reflex.
投稿者 prime-watanabe : 14:30
Michiel Helmes, Ph.D.
Michiel Helmes, Ph.D.
Research Associate
University of Oxford
Department of Physiology, Anatomy and Genetics
http://www.dpag.ox.ac.uk/research/cardiac_science/peter_kohl/kohl_members
ION Optix Europe
http://www.ionoptix.com/
【発表日程】 8月24日(金) A-2 Advanced Technologies Session アブストラクト
投稿者 prime-watanabe : 14:20
【講演中止(8/21)】A-1 Johnny Roughan Ph.D.
【お知らせとお詫び -8月21日】
講師の都合により、急遽下記A-1の講演は中止となりました。
ご迷惑をおかけ致しまして申し訳ありませんが、何卒ご了承頂けますようお願い致します。この中止に伴い、プログラム・タイムテーブルに変更がございます。8月24日最新のタイムテーブルは、こちらからご確認下さい。(PDFリンク)
【演題名】
Automated analysis of post-operative behaviour: a potentially useful method to rapidly identify pain and analgesic effects in mice.
手術後の振舞の自動化された解析：マウスにおいて迅速に疼痛と鎮痛効果を特定する潜在的に有用な方法
Johnny Roughan,
Pain Systems Group, Comparative Biology Centre,
University of Newcastle, UK
This study evaluated whether the automated behaviour recognition software ‘HomeCageScan’ (HCS) could detect behaviour changes and any positive analgesic effects in 2 mouse strains (C3H/HeN and C57BL/6) undergoing vasectomy.
Another objective was to test the effectiveness of HCS relative to a manual collection of behaviour data.
Control were normal mice; mice given meloxicam alone (10mg/kg-1), or either saline or meloxicam (10mg/kg-1) 30 minutes prior to anaesthesia.
The vasectomised mice received either saline or meloxicam at 5, 10, or 20mgkg-1.
Each animal was filmed for 20 minutes at one hour following surgery. Only the first 6 minutes of this footage was analysed manually. In a time-matched test HCS produced data on rearing and walking that closely resembled the results of manual analysis.
Both methods showed the behaviour of the controls was distinct from those that underwent surgery, and identified strain differences. Both HCS and the manual analysis found the C57 mice were overall more active, but not following vasectomy.
The control treatments had only minor effects compared to surgery, where both types of analysis detected markedly reduced activity.
HCS analysis showed high pre-operative dose of meloxicam reduced mobility, and the only apparent positive effects on mobility occurred in the C3H mice given 5mg/kg-1; a result that was also reflected in the manual analysis.
HCS provided a sufficiently accurate and rapid method of analysing mouse behaviour and makes more prolonged assessment practicable. This could be of considerable value for assessing post-operative behaviour and determining analgesic requirements in a range of animal models.
Johnny Roughan Ph.D. 【A-1】
8月21日：A-1の講演は講師の都合により急遽中止となりました。ご迷惑をおかけ致します。
投稿者 prime-watanabe : 13:50
Johnny V. Roughan, Ph.D.
【お知らせとお詫び -8月21日】
下記講師の講演は、都合により急遽中止となりました。
ご迷惑をおかけ致しまして申し訳ありませんが、何卒ご了承頂けますようお願い申し上げます。
===============================================================
Johnny Roughan, Ph.D.
Senior Research Associate
Pain Systems Group
School of Neurology, Neurobiology and Psychiatry
Comparative Biology Centre
The Medical School
University of Newcastle, U.K.
http://www.ncl.ac.uk/ion/staff/profile/j.v.roughan
= Publications ===============
1. Roughan, J. V. and Flecknell, P. A. (2001) Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats. Pain, 90: 65-74.
2. Roughan, J. V. and Flecknell, P. A. (2002) Buprenorphine: A reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals. Laboratory Animals, 36: 322-343.
3. Roughan, J. V. and Flecknell, P. A. (2003) Evaluation of a short duration behaviour- based post- operative pain scoring system in rats. European Journal of Pain, 7(5): 397-406.
4. Roughan, J. V.,Flecknell, P. A. and Davies, B. R. (2004) Behavioural assessment of the effects of tumour growth in rats and the influence of the analgesics carprofen and meloxicam. Laboratory Animals, 38: 286-296.
5. Roughan, J. V. and Flecknell, P. A. (2004) Behaviour-based assessment of the duration of laparotomy induced abdominal pain and the analgesic effects of carprofen and buprenorphine in rats. Behavioural Pharmacology, 15: 461-472.
6. Roughan, J. V. and Flecknell, P. A. (2006) Training in behaviour-based post-operative pain scoring in rats – an evaluation based on improved recognition of analgesic requirements. Applied Animal Behaviour Science, 96: 327-342.
7. Wright-Williams, S. L., Courade, J-P., Richardson, C. A., Roughan, J. V. and Flecknell, P. A. (2006) Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone levels and behaviour in two strains of laboratory mouse. Pain, 130: 108-118.
= Awards ===============
Awards: 2007 FELASA (Federation of European Laboratory Animal Science Associations) Award for Animal Welfare.
= Career History ===============
1990 - 1994:
PhD. Zoology
‘Physiological processes in the brain of the Mongolian Gerbil (Meriones unguiculatus)’
The Queen's University of Belfast.
1994 - 1998:
Junior Research Associate,
Comparative Biology Centre, University of Newcastle.
1998 - 2003:
Research Associate,
Comparative Biology Centre, University of Newcastle.
2003 - Present:
Senior Research Associate,
Comparative Biology Centre, University of Newcastle.
【発表日程】8月24日(金) A-1 Advanced Technologies Session アブストラクト
投稿者 prime-watanabe : 13:40
S-7 Klaas Kramer, Ph.D.
【演題名】
Animal stress before and after transport assessed with telemetry
Klaas Kramer(1), PhD, Sara Capdevila(2), PhD and Sylvia Stemkens(3), DVM
(1)Department of Safety and Environmental Affairs,
Free University, Van der Boechorststraat 1, 1081 BT Amsterdam,
E-mail: k.kramer
dienst.vu.nl;
(2)Harlan Interfauna Iberica S.L., Sant Feliu de Codines, Barcelona, Spain;
(3)Harlan Netherlands, Horst, The Netherlands
The article 5 of the Appendix A of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes ETS no 123 says that “unless the state of health of animals introduced into an establishment is satisfactory, it is recommended that they should undergo a period or quarantine ..Even the animals are seen to be sound health it is good husbandry for them to undergo a period of acclimatization before being used in procedure. The time required depends on several factors, such as the stress to which the animals have been subjected which in turn depends on several factors such as the duration of the transportation and the age of the animal. This time shall be decided by a competent person”.
In general, animals subjected to environmental changes such as being placed in a transport box, moved during several hours and placed in a new animal facility with new caretakers will react to the new situation with changes in their physiological responses, such as body weight, hormonal levels in plasma, heart rate and blood pressure. To foster good scientific practice the animal should be used in an experimental procedure after being adapted to the new situation when the physiological parameters are stable. Since the telemetry technique provides a way to obtain accurate and reliable physiological measurements from awake and freely moving animals in their own environment, it is a valuable tool to investigate animal welfare without the overlay of stress-producing factors associated with conventional techniques.
During this presentation two rodents studies will be discussed showing the time of acclimatization small laboratory animals needed after transport.
References:
1.Capdevila S. and K. Kramer et al. (2007) Note on assessing the time required for acclimatization of rats after five hours of transport to a new animal facility. Laboratory Animals 41, 255-261 (2007).
2.Stemkens S. and K. Kramer et al. (2007) The use of radio-telemetry to assess the time needed to acclimatize guinea pigs following several hours of transport. Laboratory Animals (Submitted).
Klaas Kramer, Ph.D.
S-7 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 12:10
Klaas Kramer, Ph.D.
Klaas Kramer, Ph.D.
Departmentof Health, Safety and the Environment,
Vrije Universiteit (Free University), Amsterdam, The Netherlands
IMTC bv (Microsurgical Training Centre)
CEO & Technical Director
http://www.intmtc.com/
Klaas Kramer was born on 1 march, 1951 in Haarlem, The Netherlands.
After secondary education he entered the Higher Laboratory School (HBO) where he graduated with zoology as main subject.
From August 1972 until July 1973 he worked as a technician at the Graphic Company Joh. Enschedé en Zn in Haarlem.
From September 1973 until December 1988 he worked as a research technician at the Faculty of Chemistry, Department of Pharmacochemistry, Division of Molecular Pharmacology at the Vrije Universiteit, Amsterdam, The Netherlands.
From December 1988 until January 2000 he worked at the same Division as a senior research assistant. He received his BSc in December 1998 at the Hogeschool van Amsterdam (HLO) with biochemistry as main subject.
On April 27th, 2000 he defended his PhD thesis with the title: "Applications and Evaluation of Radio-Telemetry in Small Laboratory Animals" successfully at the University of Utrecht, The Netherlands. He wrote his PhD thesis under supervision of the promotors Prof. dr. Bert van Zutphen from The Department of Laboratory Animal Science, Veterinary Faculty, University of Utrecht, The Netherlands, and Prof. dr. René Remie from The Department of Pharmacology, University of Groningen, The Netherlands.
From January 2000 he started as researcher in the field of Animal Welfare (Reduction, Refinement and Replacement) at The Department of Animals, Science and Society, Division of Laboratory Animal Science, Veterinary Faculty, University of Utrecht, The Netherlands and as co-worker at the Section Animal Welfare from the Department of Safety and Environmental Affairs at the Vrije Universiteit, Amsterdam, The Netherlands.
He is first author and co-author of 50 full scientific papers and 64 scientific abstracts related to the topic of his PhD thesis, which are published in international scientific journals.
He also presented more then 100 lectures, related to the topic of his PhD thesis, at scientific meetings all over the world and he recently received three national awards and the Nathan R. Brewer Scientific Achievement International Award for his radio-telemetry work as described in his PhD thesis.
He also published another 23 full scientific papers and another 26 scientific abstracts in international journals in the field of Molecular Pharmacology.
He is CEO and technical Director of the International Microsurgical Training Centre (IMTC).
IMTC combines industry and academia experience in teaching microsurgical and experimental techniques including telemetry. For more detailed information about IMTC, please visit the IMTC website (www.intmtc.com).
He is also CEO of Research and Telemetry B.V. (RaT B.V.)
【発表日程】
8月23日(木) U-2 Telemetry Users Group Meeting アブストラクト
8月24日(金) S-7 Symposium アブストラクト
投稿者 prime-watanabe : 11:30
S-6 Robert Hamlin, DVM, Ph.D.
【演題名】 Giraffes would make great fighter pilots, bats great cardiologists… and please give me a heart that is part guinea pig, part spider, part goat, and part rat!
キリンは優れた戦闘機パイロットになり、コウモリは優れた心臓専門医になる；
私にモルモット、クモ、ヤギ、ラットの心臓をください！
Robert L Hamlin, DVM, PhD, DACVIM (Cardiology/Internal Medicine)
Stanton Youngberg Professor of Physiology/Pharmacology,
Professor of Biomedical Engineering,
Professor of Ross Heart and Lung Research Institute,
The Ohio State University; Scientific Director, QTest Labs, LLC
We —human beings— are lucky we’re so smart, because, when compared to other animals, we certainly lack many anatomical and physiological features that suite us to survive. For example, the giraffe is not affected by postural change because it wears a natural anti-gravity suite, echolocation by bats allows them to interrogate moving targets with enormous precision, the spider heart can never develop diastolic dysfunction because it possess an active relaxation, the guinea can never have a heart attack because it possesses spectacular coronary collateral channels, the goat heart can never develop dysynchorny or bundle branch block because of its collateral branches between main left and right and nearly complete endocardial to epicardial penetration of Purkinje fibers, and the rat cannot develop torsades de pointes because it lacks IKR channels. So why is it that man survives to 2.4 billion heart beats, cats to 1.2 billion, and all other animals to 700 million in a life time? Because we’re so smart and appear not to need those superior anatomical and physiological properties.
Robert Hamlin, DVM, Ph.D.
S-6 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 11:30
S-5 Marc D. Feldman, M.D.
【演題名】
Advances in invasive murine cardiovascular studies
ネズミを用いた侵襲性の心血管研究における進歩
1Rodolfo J. Trevino, 4Douglas L. Jones, 3John Porterfield, 3Anil Kottam, 2Gary B. Chisholm, 1Daniel Escobedo, 1Amanda Barton, 3Jon Valvano, 3John Pearce, 1,3Marc D. Feldman
1- Department of Medicine, University of Texas Health Science Center in San Antonio, Texas;
2- Department of Epidemiology and Biostatistics, University of Texas Health Science Center in San Antonio, Texas;
3- Department of Electrical Engineering, School of Engineering, University of Texas at Austin, Texas; and
4- Departments of Physiology, Pharmacology and Medicine, University of Western Ontario, Canada.
There is interest in generating accurate invasive left ventricular (LV) pressure-volume (PV) relations in gene altered mice. The current systems are based upon the magnitude of the conductance signal (old fashion conductance). There are two limitations which limit this approach. First, the electric field is not homogenous and thus the conductance to volume relationship is non-linear. Second, there is leakage of current into the myocardium which contaminates the conductance signal, when only the blood signal is desired. We have developed a solution to the second problem. We propose the use of complex admittance as a new approach to generate LV PV relations with removal of instantaneous parallel conductance. The admittance approach takes advantage of myocardium having both real and imaginary components, whereas blood only has real components, which allows us to remove the myocardium from the combined blood-myocardial signal. Such an approach eliminates the use of hypertonic saline in the mouse, and can generate absolute ventricular function measures such as end-systolic elastance, allowing mouse-to-mouse comparisons for the first time. A comparison of magnitude only conductance at 2 kHz versus admittance at 30 kHz derived LV PV relations acquired at the same time in the same murine heart will be presented.
Due to the demanding design constraints created by the intact murine heart, developing a micro-manometer pressure sensor that has little temperature or pressure drift, a flat frequency response to at least ten times the murine heart rate, and adequate sensitivity has been difficult. Millar Instruments successfully solved this problem in 1998, and since that time, the 1.4 F Millar micro-manometer pressure sensor has served as the “gold standard” for invasive cardiovascular murine studies. Recently, Scisence Inc. has developed a competing micro-manometer pressure sensor for cardiovascular applications in the mouse. It was designed with the sensor being recessed inside the protective housing with a circumference of 1.2 F. However, despite use of this new Scisense pressure sensor by the cardiovascular research community, the Scisense sensor has not been previously tested in a rigorous fashion to validate its use in the murine heart. We demonstrate that both sensors had equivalent in vitro swept frequency response over time, frequency response at 100mmHg, and catheter step response to transient pressure drop. Both sensors also performed similarly during in vivo dose-response studies to iv isoproterenol, and simultaneous placement of both micro-manometer pressure sensors in the same intact murine heart. However, the Millar sensor had slightly greater in vitro temperature drift and in vivo pressure drift. We conclude that both sensors are equivalent, and that the Scisense pressure sensor represents an alternative to the Millar micro-manometer pressure sensor.
Marc D. Feldman, M.D. (University of Texas Health Science Center )
S-5 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 10:40
Marc D. Feldman, M.D.
MARC DAVID FELDMAN, M.D.
http://medicine.uthscsa.edu/faculty.asp
http://cardiology.uthscsa.edu/
» Recent Biography «
= Faculty Positions ===============
2006-present
Director, Cardiac Catheterization Laboratories,
University of Texas Health Science Center at San Antonio
2001-present
Associate Professor of Physiology,
University of Texas Health Science Center at San Antonio.
1998-present
Adjunct Faculty, Biomedical Engineering,
combined University of Texas at San Antonio – University of Texas HSC at San Antonio
1998-present
Staff Physician, South Texas Veterans Health Care Systems
1998-present
Adjunct Associate Professor,
University of Texas School of Biomedical Engineering, Austin, Texas
1998-present
Associate Professor of Medicine, Division of Cardiology,
University of Texas Health Science Center at San Antonio
1994-1998
Associate Professor of Medicine, Division of Cardiology,
University of Pittsburgh School of Medicine
1993-1994
Associate Professor of Medicine, Cardiovascular Division,
University of Virginia School of Medicine
1987-1993
Assistant Professor of Medicine, Cardiovascular Division,
University of Virginia School of Medicine
= Publications ===============
» Articles «
Over 60 articles have been published.
Wei C-L, Valvano JW, Feldman MD, Nahrendorf M, Peshock R, Pearce JA.
Volume catheter parallel conductance varies between end-systole and end-diastole. IEEE Transactions on Biomedical Engineering. In press 2007
Mani G, Feldman MD, Patel D, Agrawal CM.
Coronary stents: A materials prospective.
Journal of Biomaterials Research. 2007 28 (9): 1689-1710.
Colston JT, Boylston WH, Feldman MD, Jenkinson CP, De La Rosa S, Barton A, Trevino RJ, Freeman GL, Chandrasekar B.
Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload. Biochemical Biophysical Research Communications. 2007; 354 (2); 552 -558.
Oh J, Feldman MD, Kim J, Sanghi P, Kang, HW, Milner TE.
Magneto-motive detection of tissue-based macrophages by differential phase optical coherence tomography.
Lasers in Surgery and Medicine. 2007; 39 (3): 266-272.
Ayon A, Cantu M, Chava, K, Agrawal, M, Feldman, MD, Johnson, D, Patel, Marton, D, Shi, Emily. Drug loading of nanoporous TiO2 Films. Journal of Biomedical Materials. 2006 (4): L11-L15.
» Books «
Cilingiroglu M, Oh J-H, Sanghi PK, Kemp NJ, Thomsen S, Milner TE, Feldman MD. Clinical Lessons from Optical Coherence Tomography Imaging of Apo E Knockout Mice. Handbook of Optical Coherence Tomography in Cardiovascular Research.
Edited by E. Regar, TG van Leeuwen and P Serruys. 2006.
= Editorial Consultant ===============
Circulation, Circulation Research , Journal of the American College of Cardiology, Catheterization and Cardiovascular Diagnosis, American Journal of Physiology, European Heart Journal, Cardiovascular Drugs and Therapy, Journal of Applied Physiology, Journal of Molecular and Cellular Cardiology
【発表日程】 8月24日(金) S-5 Symposium アブストラクト
投稿者 prime-watanabe : 10:35
S-4 Attila Kovacs, M.D.
【演題名】
New Developments in Small Animal Cardiovascular Research using High-Resolution Micro-Ultrasound Imaging.
高解像度マイクロ超音波イメージングを用いた、小動物心血管研究における新たな進展
Major research efforts are being devoted to refine echo techniques and to find new applications for increasingly sophisticated non-invasive evaluation of cardiovascular phenotypes in genetically manipulated mouse models of human cardiovascular diseases.
The purpose of this presentation is to share with the audience some of the recent experiences with the use of the Vevo 770 system in the Mouse Cardiovascular Phenotyping Core laboratory at Washington University in Saint Louis Missouri. This laboratory has been engaged in this type of work for over 10 years, and during this time there has been a remarkable explosion in the numbers and especially in the sophistication of the techniques as well as genetic manipulation of mice.
This parallel development, and arguably, mutually beneficial interaction has lead to the establishment and, by now, virtual requirement of phenotyping laboratories at a variety of academic institutions and pharmaceutical companies.
These laboratories, such as the one at Washington University, employ a variety of invasive and non-invasive techniques to study the cardiovascular system in mice.
Due to its remarkable versatility, echocardiography plays a critical role in this process.
The main goal of the presentation is to show how the use of the Vevo 770 system, even in a short period of time, has had and continues to have a major impact on the phenotyping work in the laboratory.
The presentation will show a few examples of cardiac and vascular models, surgically created or as a result of genetic manipulation, and through these examples demonstrate that comprehensive evaluation of cardiovascular structure, function and now through molecular imaging, even the non-invasive study of molecular mechanisms is currently possible in many if not most of these experimental conditions.
Examples will be shown where the improved imaging capabilities of the Vevo system compelled the users to reevaluate well established and previously validated models, such as aortic banding to study pressure overload LV hypertrophy and coronary ligation model to study ischemic heart disease, as well as new areas of application including most of the vascular work, which previously has not been possible using clinical imagers.
And finally, results of preliminary experiments using different types of microbubble contrast will be shown to demonstrate the great potential of these agents in the quantitative evaluation of myocardial perfusion and non-invasive in vivo elucidation of molecular mechanisms underlying common cardiovascular diseases such as myocardial infarction and atherosclerosis.
Attila Kovacs, M.D.
S-4 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 10:00
Attila Kovacs, M.D.
Attila Kovacs, M.D.
Associate Professor of Medicine
Cardiovascular Division, Department of Medicine
Washington University , School of Medicine
Director, Mouse Cardiovascular Phenotyping Core
Center for Cardiovascular Medicine
http://cardiology.wustl.edu/faculty/akovacs.html
http://mcpc.wustl.edu/echo/echo.htm
= Publications ===============
Over 40 articles has been published.
Holland MR, Kovacs A, Posdamer SH, Wallace KD, Miller JG. Anisotropy of apparent backscatter in the short-axis view of mouse hearts. Ultrasound Med Biol. 2005;31:1623-9.
DeBosch B, Lupu TS, Weinheimer C, Kovacs A, and Muslin AJ. Akt1 is required for physiologic cardiac growth. Circulation, 2006;113:2097-104.
Rovner A, Valika AA, Kovacs A, Kates AM. Possible paradoxical embolism as a rare cause for an acute myocardial infarction. Echocardiography. 2006 May;23(5):407-9.
Lau JM, Jin X, Ren J, Avery J, Debosch BJ, Treskov I, Lupu TS, Kovacs A, Weinheimer C, Muslin AJ. The 14-3-3{tau} Phosphoserine-Binding Protein Is Required for Cardiomyocyte Survival. Mol Cell Biol. 2007 Feb;27(4):1455-66.
Ma X, Liu Y, Tittiger M, Hennig A, Kovacs A, Popelka S, B Wang, Herati R, Bigg M, Ponder KP. Improvements in mucopolysaccharidosis I mice after adult retroviral vector-mediated gene therapy with immunomodulation, Molecular Therapy, in press.
Yang J, Sambandam N, Han X, Gross RW, Michael Courtois M, Kovacs A, Febbrai M, Finck BN, Kelly DP. CD36 Deficiency Rescues Lipotoxic Cardiomyopathy. Circ Res, in press.
= Education ===============
1987 - 1990
Intern and Resident in Internal Medicine
New York Medical College, Program B
Metropolitan Hospital Center, New York, NY
Awarded "Certificate of Merit: in recognition of exceptional achievement
as a PGY-II resident in 1989"
1990 - 1991
Chief Resident in Internal Medicine
New York Medical College, Program B
Metropolitan Hospital Center, New York, NY
1991 - 1993
Clinical Postdoctoral Fellow in Cardiology
Division of Cardiology, Department of Medicine,
University of Missouri-Columbia, Columbia, MO
1993 - 1994
Postdoctoral Fellow
Division of Cardiology and
Dept. Molecular Microbiology and Immunology
University of Missouri-Columbia, Columbia, MO
1995 - 1996
Advanced Echocardiography Fellow in Cardiology
Division of Cardiology, Department of Medicine
Washington University School of Medicine, St. Louis, MO
【発表日程】 8月24日(金) S-4 Symposium アブストラクト
投稿者 prime-watanabe : 10:00
2007年08月23日
T-4 Blair Poetschke
【演題名】 Advancing Pressure-Volume Measurements in Rodents
Blair Poetschke
President, Scisense Inc.
Over the past decade, the mouse has become one of the most prominent species used in cardiovascular research labs. They are easy to maintain, relatively inexpensive and have very short gestational periods. Most importantly, the mouse genome has been highly characterized and can very easily be manipulated to study specific diseases. The biggest challenge for Scientists, however, has been to find suitable tools to perform classical physiological studies with these small animals. Scisense Inc., a Canadian medical device company, has responded to this need by manufacturing a full line of catheter-based products specifically for use in the murine model of cardiac dysfunction.
Of particular interest is our state-of-the-art pressure-volume (PV) system for use in mice. Since the 1970’s, the pressure-volume (PV) loop has steadily become the gold standard as a means to study myocardial contractility, compliance, muscle energetics and other important quantitative measurements of cardiac function in vivo. These measurements, however, have only been possible in the larger animal model, until now. Our smallest catheter measures only 1.2F (0.4 mm) in diameter at the tip and 0.8F (0.27 mm) along the tube. The standard ring spacing is 4.5 mm which is suitable for mice in the 20+ gram range. A customized electrode ring spacing of 3.5 mm can be provided to study slightly smaller and younger animals.
Typical parameters acquired by the Scisense mouse PV system include: heart rate, maximum and minimum pressure, maximum and minimum volume, end-systolic and end-diastolic pressure/volume, stroke volume, cardiac output, ejection fraction, stroke work and PV loop derived parameters of elastance (ESPVR) and compliance (EDPVR). Most of these parameters can be obtained in real-time – from a single instrument!
The Scisense pressure-volume (and pressure) catheter has been uniquely designed to allow for easy insertion and maneuverability, to reduce trauma during insertion into the left ventricle and to minimize impact on aortic flow and central hemodynamics. Scientists previously unfamiliar with surgical procedures for mice have been able to quickly learn the techniques to insert the Scisense pressure and pressure-volume catheters, due their small size and flexible, but strong, construction.
The hardware component of the mouse PV system amplifies and conditions the signals from the sensors at the tip of the catheter. Signal outputs are analog voltages that can be directly acquired by any computerized acquisition system.
Finally, Scisense also manufactures an assortment of pressure, dual pressure, electrophysiology (EP) and PV catheters for mice, rats, rabbits and larger animal models. All pressure transducers contain a high-fidelity pressure sensor which is recessed and insensitive to side impacts from the left ventricle and vessel walls. High-fidelity pressure sensors offer high frequency response, are not prone to motion artifact or overshoot as with conventional fluid-filled catheters and are vented to atmosphere to correct for barometric pressure.
投稿者 prime-watanabe : 17:15
Blair Poetschke
Blair Poetschke
President
Scisense Inc.
【発表日程】 8月23日(木) T-4 Technical Session アブストラクト
投稿者 prime-watanabe : 17:05
T-3 Philippe Zitoun
【演題名】 Addressing new trends in Safety Pharmacology with new advanced tools from non-invasive non-implantable ECG measurements to advanced in-vitro early safety.
Philippe Zitoun,
President of NOTOCORD Systems,
"Speeding up Research, Empowering Science".
In the last 10 years, cardiac/respiratory safety pharmacology has become one of the most computerized research activities developed by the pharmaceutical industry. The cost of operation, data management, performance and productivity in all research areas are some of the new key issues for Safety/Tox studies.
NOTOCORD is covering these new challenges and will present:
- a unique non-invasive ECG recording and analysis solution combining efficiency with high performance qualification.
- new solutions to go further in in-vitro early safety, as hemodynamic, arrhythmia analysis and EEG measurements.
投稿者 prime-watanabe : 16:45
Philippe Zitoun
Philippe Zitoun
CEO, NOTOCORD Systems SAS
【発表日程】 8月23日(木) T-3 Technical Session アブストラクト
投稿者 prime-watanabe : 16:45
Michael C. Girand
Michael C. Girand
DSI-Ponemah Marketing Product Manager
Data Sciences International
QUALIFICATIONS
13 years pharmaceutical experience
· Manager/supervisor · 6 years experience
· 3 years sales experience
· Extensive telemetry surgery and data acquisition experience
· Study director, department trainer, and computer skills
· Strong analytical and organizational skills
· Excellent presentation and communication skills
· Firm knowledge protocol development and GLP guidelines
EDUCATION
UNIVERSITY OF PHOENIX
Mater of Business Administration, 2005
MICHIGAN STATE UNIVERSITY, College of Natural Science, 1992
B.S. Zoology Emphasis: Cellular and Developmental Biology
EXPERIENCES
PFIZER GLOBAL R&D, Ann Arbor, MI - 1991 – 2003
2001 - 2003 : Scientist, Safety Pharmacology, Pfizer Global Research & Development, Ann Arbor, Michigan
1998 - 2001 : Senior Associate Scientist, Safety Pharmacology, Pfizer Global Research & Development, Ann Arbor, Michigan
1997 - 1998 : Associate Scientist, Safety Pharmacology, Warner-Lambert / Parke-Davis, Ann Arbor, Michigan
1995 - 1997 : Senior Assistant Scientist, Pathology and Experimental Toxicology, Warner-Lambert / Parke-Davis, Ann Arbor, Michigan
1993 - 1995 : Assistant Scientist, Pathology and Experimental Toxicology, Warner-Lambert / Parke-Davis, Ann Arbor, Michigan
1992 - 1993 : Laboratory Assistant, Cardiovascular, Warner-Lambert / Parke-Davis, Ann Arbor, Michigan
1991 – 1992 : Laboratory Assistant, Atherosclerosis, Warner-Lambert / Parke-Davis, Ann Arbor, Michigan
CERTIFICATIONS
Hand on Implantable Telemetry Techniques for Laboratory Animals (AALAS/DSI),
University of Michigan Management I & II,
University of Michigan Leadership Practices in Action, Influence Management,Resolving Conflict, Behavioral Interviewing,Technical Report Writing, Civil Treatment for Managers,
Professional Selling Skills (Achieve Global)
PUBLICATIONS
Olivier NB, Eyster GE, Sanders R, Cheng J, Bohart G, Girand M, Bailie M.
Atrioventricular nodal ablation and His-bundle pacing: an acute canine model for proarrhythmic risk assessment. Journal of Cardiovascular Electrophysiology, Dec; 14(12), 1356-60. (2003)
【発表日程】
8月23日(木) T-2 Technical Session アブストラクト
投稿者 prime-watanabe : 16:05
T-2 Michael C. Girand
【演題名】 Safety Pharmacology Cardiovascular Study Design and ECG Analysis
Michael C. Girand
DSI-Ponemah Marketing Product Manager
Data Sciences International
Cardiovascular Safety Pharmacology studies provide valuable insight into a drug’s adverse effects, as well as a preview of what may be observed clinically. Implantable radiotelemetry is the preferred technology for obtaining measurements in unrestrained conscious test subjects.
In this presentation, a typical Cardiovascular Safety Pharmacology study design will be outlined. In addition, market trends pertaining to standardization, data collection, and analysis will be addressed. Last, features using the Ponemah Physiology Platform will be showcased as the preferred tool for data acquisition and analysis of small and large quantities alike.
投稿者 prime-watanabe : 16:05
T-1 Robert Brockway
【演題名】 A Practical Guide to EEG Telemetry Applications
Bob Brockway
Product Planning and Business Development Manager
Data Sciences International
A brief overview will be given regarding recent DSI product releases including the 4ET, ART 4.1, the F40-TT, JET external telemetry, and NeuroScore CNS analysis software. DSI CNS solutions will be reviewed in detail including the 4ET transmitter model and the NeuroScore software. Sample study data will be presented along with the analysis process and results. The conclusion of this presentation is that DSI telemetry and NeuroScore provide an effective and efficient tool for CNS applications.
投稿者 prime-watanabe : 15:35
Robert Brockway
Marketing Manager
Data Sciences International
【発表日程】
8月23日(木) T-1 Technical Session アブストラクト
投稿者 prime-watanabe : 15:25
U-3 Hiroyoshi Sei M.D.
【演題名】 Arterial pressure rises with spontaneous apnea during REM sleep in mice
マウスのレム睡眠期に見られる無呼吸は血圧上昇を伴う
徳島大学 医学部 統合生理学講座
教授 勢井 宏義
Hiroyoshi Sei M.D.
Professor, Dept. of Integrative Physiology,
The University of Tokushima, Faculty of Medicine
睡眠時無呼吸症候群は、昼間の強い眠気を引き起こし、居眠り運転による事故などの原因となる。また、高血圧など生活習慣病との関連性も指摘されており、その予防・治療に関する研究は医学的に重要な課題の一つである。無呼吸はマウスのレム睡眠期においても観察される。一方、レム睡眠期の血圧も大きく変動し、スパイク様の昇圧が頻回に観察される。今回、EMMS社のplethysmographとDSI社のテレメトリ装置を併用し、マウス（ICR系）におけるレム睡眠期の呼吸と血圧の関連について観察した。まず、TL11M2-F20を用いて、マウスの脳波、筋電図をテレメトリで記録しながら、各睡眠段階の呼吸様式について観察した（EEG-resp群）。さらに、別の群（AP-resp群）において、TA11PA-C20を用いて、呼吸と血圧の同時測定を行った。EEG-resp群から、マウスのレム睡眠期では無呼吸が観察され、その特徴的な呼吸様式から、逆にレム睡眠期を推定できることが分かった。AP-resp群において、呼吸様式から判別したレム睡眠期では、血圧が上昇し、さらに一過性のスパイク様昇圧も観察された。呼吸回数は、レム睡眠期の初めに最低値をとり、その後、レム睡眠の継続と共に増加した。平均血圧のレム睡眠期におけるピークは、無呼吸の発生時期とほぼ一致していた。また、スパイク様昇圧は、無呼吸からおよそ2秒ほど遅れて発生していた。呼吸賦活薬であるアセタゾラミドの慢性投与は、レム睡眠期の呼吸回数を増やし、血圧の上昇を抑えた。これらの結果から、マウスのレム睡眠期では換気不全のため脳が低O2あるいは高CO2状態に陥り、それに対する化学受容器を介した昇圧反応が起こっているのではないかと仮説される。
Spontaneous apnea can be observed during REM sleep in mice. Arterial pressure (AP) during REM sleep shows large fluctuation with several phasic surges. We investigated relationship between apnea and AP surge during REM sleep using whole body plethysmograph (EMMS, UK) and telemetric devices (DSI, USA). One group of mice (EEG-resp group), we performed simultaneous recording of sleep and ventilation to estimate respiratory pattern during each sleep state. The mice were implanted with a telemetric device (TL11M2-F20) for recording electroencephalography (EEG) and electromyography (EMG). Another group of mice (AP-resp group), we recorded AP and ventilation simultaneously to observe the relationship between AP surge and impaired respiratory event during REM sleep. The mice were implanted with a telemetric device (TA11PA-C20) for recording AP. For both group, after 10-day recovery period, each mouse was put into a whole body plethysmography chamber and the receiver for telemetric device was put under the chamber. In both group, the telemetric and respiratory signals were captured by CED 1401 data processor (CED, UK), and stored on the hard disk. Off-line analysis was done using the Spike 2 analyzing program (CED, UK). In ICR mice, AP elevated rapidly and showed a peak in the early part of REM sleep, while frequency of ventilation gradually increased and the peak was observed at the end of REM sleep. Temporal position of the spontaneous apnea corresponded with the peak of AP. The apnea was followed by the phasic surge of AP with about 2-sec delay. Furthermore, chronic treatment of acetazolamide, carbonic anhydrase inhibitors, increased the frequency of ventilation and suppressed the AP increase during REM sleep. These data suggest that, during REM sleep, hypoxia and/or hypercapnia caused by impaired ventilation may induce the increase of AP even in the normal mice.
投稿者 prime-watanabe : 14:50
Hiroyoshi Sei, M.D., Ph.D.
Hiroyoshi Sei, MD, PhD
3-18-15 Kuramoto, Tokushima
Tokushima 770, JAPAN
Phone: +81 88 633 7056
Fax: +81 88 633 9251
e-mail: seibasic.med.tokushima-u.ac.jp
WORK HISTORY
Professor of Physiology (2007 to present)
Department of Integrative Physiology,
Institute of Health Biosciences,
The University of Tokushima Graduate School
Associate Professor of Physiology (2001-2007)
Assistant Professor of Physiology (1994-2001)
Research Associate of Physiology (1988-1994)
EDUCATION
The University of Tokushima Graduate School (1984-1988) – Ph.D.
The University of Tokushima, School of Medicine (1978-1984) – M.D.
LICENSES / CERTIFICATIONS
Medical Doctor: Japan #280028
Japanese Sleep Research Society: Sleep Medical Doctor #270
PROFESSIONAL ORGANIZATIONS
Society for Neuroscience (Member)
International Behavioral Neuroscience (Member)
Physiological Society for Japan (Councilor)
Japanese Society of Sleep Research (Councilor)
【発表日程】 8月23日(木) U-3 Telemetry Users Group Meeting アブストラクト
投稿者 prime-watanabe : 14:50
U-2 Klaas Kramer, Ph.D.
【演題名】
Surgical Approaches for Rodent Telemetry
Klaas Kramer, Free University, Amsterdam, The Netherlands,
k.kramerdienst.vu.nl
Research trends over past 20 years have shown decreases in the numbers of young scientists trained to conduct animal research. Shifts in funding sources, emphasis on biochemistry and molecular biology, increased costs and public concern about animal research and animal welfare issues, and regulation of animal research have contributed to this decrease. Some of these trends are now reversing, placing new emphasis upon animal research. For example, ICH Guidelines on Safety Pharmacology for Human Pharmaceuticals (S7A) explicitly request that unanaesthetized, chronically instrumented animal models be used in pharmaceutical development after 2000.
The combination of these trends has led to new realities:
• Animal research is increasingly conducted in smaller (rodent) species
• Animal researchers must be specifically trained in new techniques for small animals to be in compliance with new regulations
Implications for animal research in 2007 and beyond:
• Scientists must be trained to design appropriate study designs
• Study Directors/Monitors must be trained to develop protocols & to supervise procedures
• Technicians must be trained in microsurgical and experimental procedures including technical aspects (aseptic procedures, anaesthesia, analgesia, etc.)
• Good Laboratory Practices Regulations (CFR 21/58) require documentation of training of study personnel to conduct specific study procedures.
This presentation will review surgical approaches for implantation of radio-telemetry transmitters in small laboratory animals (rats and mice) and during the presentation the following items will be discussed:
• Aseptic conditions
• Anaesthesia and analgesia
• Surgical instruments
• Implantation procedures for ECG and blood pressure transmitters
• Postoperative care
• Surgical problems
Literature:
Book: Manual of Microsurgery on the laboratory rat. J.J. van Dongen, R. Remie, J.W. Rensema and G.H.J. van Wunnik. Editor: J.P. Huston; Elsevier, The Netherlands. ISBN 0-444-81138-9
Klaas Kramer, Ph.D.
U-2 Telemetry Users Group Meeting 発表演題・アブストラクトを掲載しました。
投稿者 prime-tazaki : 14:20
Masayoshi Kuwahara, Ph.D.
Masayoshi Kuwahara, Ph.D.
1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
Phone: +81-3-5841-5391
Fax: +81-3-5841-5391
E-mail: akuwammail.ecc.u-tokyo.ac.jp
WORK HISTORY
Associate Professor (1998-present)
Department of Comparative Pathophysiology,
Graduate School of Agricultural and Life Sciences,
The University of Tokyo
Assistant Professor (1988-1998)
Department of Comparative Pathophysiology,
Graduate School of Agricultural and Life Sciences,
The University of Tokyo
Research Fellow(1988-1990)
Department of Pathology,
Schools of Medicine and Dentistry,
Georgetown University (USA)
Education:
Doctor course (1985-1987)
Department of Animal Environmental Physiology,
Faculty of Agriculture, The University of Tokyo
Master course (1983-1985)
Department of Animal Environmental Physiology,
Faculty of Agriculture, The University of Tokyo
Undergraduate (1979-1983)
Faculty of Agriculture, Tohoku University
Membership of academic societies:
American Thoracic Society
International Society of Electrocardiology
Japanese Society of Electrocardiology
The Japanese Society of Veterinary Science
Japanese Society of Zootechnical Science
Japanese Association for Laboratory Animal Science
Japanese Society of Equine Science
Japanese Society of Veterinary Cardiology
【発表日程】 8月23日(木) U-1 Telemetry Users Group Meeting アブストラクト
投稿者 prime-watanabe : 13:50
S-3 Michael Markert
【演題名】
The value added by using the new Notocord ECG31p analyzer in cardiac safety pharmacology studies in the conscious primate.
Michael Markert
Principal Scientist, Lab-Head cardiovascular safety, General Pharmacology,
Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Measuring correctly the ECG (expecially the QT interval) in freely moving primates is challenging. However, models are available where one can get amazing results by using the appropriate hardware and software equipment. In this presentation you will hear what the impact of the new Notocord Hem primate analyzer on the ECG detection is and see in a case study why this improvement helped to improve the quality of a given design.
Mr.Michael Markert (Boehringer Ingelheim Pharma GmbH & Co KG)
S-3 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 12:00
Michael Markert
Michael Markert
Principal Scientist, Lab-Head cardiovascular safety, General Pharmacology,
Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
http://www.boehringer-ingelheim.com/
= Experience ===============
Working since 15 years in the field of Telemetry Research.
Large animal telemetry research (dogs, primates, minipigs).
Program committee 2005, Safety Pharmacology Society.
Speaker 2006, Safety Pharmacology Society.
Various talks at QT strategy meetings.
= Publications ===============
Continuous assessment of multiple vital physiological functions in conscious freely moving rats using telemetry and a plethysmography system. 2000. Journal of Pharmacological and Toxicological Methods 43 (3), pp. 211-217.
A novel propellant-free inhalation drug delivery system for cardiovascular drug safety evaluation in conscious dogs. 2004. Journal of Pharmacological and Toxicological Methods 50 (2), pp. 109-119.
Developing a strategy for the nonclinical assessment of proarrhythmic risk of pharmaceuticals due to prolonged ventricular repolarization. 2004. Journal of Pharmacological and Toxicological Methods 49 (3), pp. 159-169.
Correcting the QT interval for changes in HR in pre-clinical drug development. 2004. Methods of Information in Medicine 43 (5), pp. 445-450.
Optimizing the experimental environment for dog telemetry studies. 2006. Journal of Pharmacological and Toxicological Methods 54 (2), pp. 141-149.
The value added by measuring myocardial contractility ‘in vivo’ in safety pharmacological profiling of drug candidates. Article in press. Journal of Pharmacological and Toxicological Methods.
= Education ===============
Biologist, trained surgeon/anesthetist.
ECG/cardiovascular education at Ohio State University, Columbus, US
College of Veterinary Medicine, Prof. Robert Hamlin.
【発表日程】 8月23日(木) S-3 Symposium アブストラクト
投稿者 prime-watanabe : 11:50
S-2 Craig R. Hassler, Ph.D.
【演題名】 State of the Art and future directions of Safety Pharmacology
安全性薬理の最先端と今後の方向性
Craig R. Hassler PhD
Manager of Safety Pharmacology
Battelle Columbus, Ohio
The ICH guideline (S7A) on Safety Pharmacology has created tremendous scientific activity in evaluating the cardiovascular, pulmonary and CNS systems for potential for undesirable pharmacodynamic effects prior to first use in man. This guidance specifically indicated that unrestrained animals chronically instrumented with telemetry are a preferred model. Safety Pharmacology needs have spurred continuing enhancements in telemetry instrumentation and application. Enhancements have included for example: capability to evaluate contractility, intra cardiac electrodes for enhanced ECG evaluation, the ability to measure pulmonary resistance monitoring of EEG activity for sleep cycle disruption evaluation. Improved R&D productivity is vital for the pharmaceutical industry. All areas of pharmaceutical research including Safety Pharmacology will have to improve. Possible improvements include: Reduction in the number of studies performed, Refinement of the present methods or Replacement with alternative models.
This presentation will review state of the art methods and examples of methods that refine the experimental method or reduce the number of animals required. The number of studies required can be reduced if cardiovascular and pulmonary studies are simultaneously in the same animals. Using dogs or monkeys appropriately conditioned to restraint, it is possible to utilize telemetry for collection of hemodynamic data and plethysmography for collection pulmonary function. The blood pressure and heart rates of restrained animals are somewhat different from those obtained from unrestrained animals. However, the cardiovascular conclusions that would be derived from the restrained animals are unlikely to alter the cardiovacular conclusions.
Pre-clinical cardiac safety is typically conducted in healthy sedentary mature young research animals. However, drugs are never administered only to healthy and/or sedentary people Cardiac related orthostatic hypotension and stress intolerance are adverse effects noted during clinical trials consequently, using animal models more relevant to the treatment population may predict potential liabilities (or benefits) of a candidate compound not observable in sedentary animals. The effects of exercise and heart failure upon drug related cardiovascular alterations were evaluated in a dog model. Carvedilol and Enalipril were administered in modest doses individually and in combination. Alterations of blood pressure, heart rate and contractility were determined during both rest and treadmill exercise in normal and heart failure animals. Exercise and heart failure individually or in combination altered the cardiovascular responses of the test articles. The data suggest that such models may provide safety information more relevant to the intended clinical population.
Craig R. Hassler, Ph.D.
S-2 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 11:10
Craig R. Hassler, Ph.D.
Craig R. Hassler, Ph.D.
Education
B.S. - 1963 - Northwestern University (Biology)
M.S. - 1965 - DePauw University (Zoology)
Ph.D. - 1969 - Loyola University (Cardiovascular Physiology)
Employment
Manager, Safety Pharmacology,
Battelle, Columbus, Ohio – October 1991 to present.
Battelle Scientist since 1970
http://www.battelle.org/
Present Responsibilities
Dr. Hassler's present duties include directing efforts in safety pharmacology and physiology. A wide variety of studies, especially those involving cardiovascular, pulmonary and central nervous system endpoints, are performed. Contemporary instrumentation is utilized for the measurement of numerous parameters. Further, Dr. Hassler directs complex GLP toxicology studies, especially those that incorporate physiologic measurements or other unusual endpoints.
Cardiovascular safety pharmacology studies are performed for the pharmaceutical industry and government in both anesthetized and awake preparations. For awake preparations, radiotelemetry is frequently the preferred method of data collection. The most common parameters measured are blood pressures, heart rate, and ECG. Implantable radiotelemetry was pioneered for GLP safety pharmacology studies. Further, telemetry methods have been developed for measurement of left ventricular pressures (for contractility measurements), pulmonary arterial pressure, intra thoracic pressure and intra cardic electrograms. Anesthetized animal studies are performed when required. A wide variety of pulmonary function studies are performed including measurement of pulmonary function including resistance via phethysmography for safety pharmacology (often in conjunction with cardiovascular measurements) and inhalation toxicology studies, and forced maneuvers. State of the art laboratories employing automated data collection techniques are employed. The studies are normally conducted in compliance with GLP regulations. Dr. Hassler has numerous publications and presentations in safety pharmacology and physiology.
Memberships
American Physiological Society
The Institute of Electrical and Electronics Engineers
Safety Pharmacology Society
【発表日程】
8月23日(木) S-2 Symposium アブストラクト
投稿者 prime-watanabe : 11:00
S-1 Robert Hamlin, DVM, Ph.D.
【演題名】 Potential cardiovascular targets for manifestation of drug-induced toxicity. 薬物性毒性の症状発現に関する潜在的な心血管標的
Robert L Hamlin, DVM, PhD, DACVIM (Cardiology/Internal Medicine)
Stanton Youngberg Professor of Physiology/Pharmacology, Professor of Biomedical Engineering, Professor of Ross Heart and Lung Research Institute, The Ohio State University; Scientific Director, QTest Labs, LLC
No risk profile is complete unless potential toxic effects on all important parameters of physiological function are investigated. Electrophysiological effects—particularly on ventricular repolarization—have consumed the pharmaceutical industry and regulatory agencies, but in the US, fewer than 15,000 persons die each year from drug-induced torsades de pointes, where as a 2 mm Hg increase in systemic arterial pressure translates to 7% increases in death from stroke and from heart failure. Since more than 5 million persons have heart failure and more than 70 million are hypertensive.
Important properties of cardiovascular function that should be interrogated to achieve necessary risk assessment are:
| A | Electrophysiological
|
||||||||
| B | Cardiac
|
||||||||
| C | Vascular and integrative
|
These parameters can be explored using state-of-the-art technology (e.g., ECG, electrography, manometry, ECHO/Doppler, Tissue Doppler, heart rate response to tilt) in common use in both physiology and clinical laboratories, and regional circulations and vascular resistances can be measured by microsphere technology. It may be necessary to monitor some physiological parameters under physiological conditions (e.g., sleep, excitement, exercise) achieved using radiotelemetry. Furthermore since drugs are given to persons with various pathological substrates as well as genetic and structural polymorphisms which might render them sensitive to drug toxicity, it is essential to consider using animals with such heterogeneities. Finally since drug effects may vary between day and night and some drugs are given to achieve cmax’s at either day or night, it may be important to investigate drug toxicity by giving drugs at the time of day for which they are intended. This emphasizes the need for chronic monitoring. Robert Hamlin, DVM, Ph.D.
S-1 Symposium 発表演題・アブストラクトを掲載しました。
投稿者 prime-watanabe : 10:30
Robert Hamlin, DVM, Ph.D.
Robert Hamlin, DVM, Ph.D, Diplomate ACVIM
Professor of Department of Veterinary Biosciences, The Ohio State University
http://vet.osu.edu/RobertHamlin.htm
【発表日程】
8月23日(木) S-1 Symposium アブストラクト
8月24日(金) S-6 Symposium アブストラクト
投稿者 prime-tazaki : 10:20
2007年08月15日
U-1 Masayoshi Kuwahara, Ph.D.
【演題名】 A novel jacketed external telemetry system for studying ECG: evaluation of QT prolongation in dogs
Masayoshi Kuwahara
Department of Comparative Pathophysiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Cardiac ventricular depolarization and repolarization are represented by the QT interval of an electrocardiogram (ECG) recording. The investigation of drug effect on the QT interval in vivo is an important issue of assessing ventricular repolarization risk. Because a novel jacketed external telemetry system was recently developed, drug-induced QT interval prolongation was quantified by using this system in the conscious beagle dog. ECGs were recorded by M-X and R-L leads that were usually used by Holter ECG recordings. E-4031, that prolongs ventricular repolarization, was selected to evaluate the sensitivity of this system. E-4031 (0.1 mg/kg. i.v.) had no effect on HR or QRS duration, but did significantly prolong the PR and QT intervals. These results were almost the same as earlier studies. Therefore, it seems that this system might be useful and convenient for evaluating the in vivo assessment of risk for QT interval prolongation.
投稿者 prime-watanabe : 11:59
2007年08月04日
昼食会場・休憩会場のご案内
== ご昼食会場のご案内 ==
8月23日（木）、24日（金）、両日ともブッフェ形式のご昼食を
お一人様 500円 にてご用意しております。
午前の部終了時、ホワイエにてチケットを販売しますので、
代金をお支払い頂き、引き換えにチケットをお受け取り下さい。
昼食会場入り口にてチケットをお渡し下さい。
23日（木）：レストランJ-bien（講道館地下1階）
>>地図
24日（金）：スカイホール（文京シビックセンター26階）
>>場所
== ご休憩会場のご案内 ==
ペットボトルドリンクのご用意がございます。ご聴講されない時間帯にご利用くださいませ。
23日：4F シルバーセンター会議室B（文京シビックセンター4階）
24日：3F 会議室 (文京シビックセンター3階、螺旋階段を上った奥です)
>>場所
投稿者 prime-tazaki : 17:12