THE BRITISH SOCIETY FOR CARDIOVASCULAR RESEARCH QUARTERLY BULLETIN

September 1989 Volume 2 Number 4

CONTENTS Editorial: 2 New BSCR Committee: 2 Letter from the Secretary: 3 BSCR Meeting Announcements Cellular Mechanisms in Cardiac Hypertrophy and Failure: 4 Blood Borne Factors in Myocardial Ischaemia: 4 ISHR Meeting Report 10th European Secrion Meeting, Rotterdam: 5 The Research Defence Society: 6 Book Review Atlas of Congenital Cardiac Surgery (Paul E. Ebert): 7 Job Advertisements: 8

2

The British Society for

Cardiovascular Research QUARTERLY BULLETIN

Edited by: Metin Avkiran

Michael J. Curtis

Please address all correspondence to: The Editors,

BSCR Quarterly Bulletin Cardiovascular Research

The Rayne Institute St Thomas' Hospital London SEl 7EH

Telephone: 01-928 9292 ext. 3374

The British Society for

Cardiovascular Research COMMITTEE MEMBERS

Chairman: David J. Hearse

Secretary: Anne-Marie L. Seymour

Treasurer: Allan S. Manning

Committee: Mark Boyett

Stuart Cobbe* Susan Coker George Hart*

Andrew C. Newby Alan J. Williams

* denotes clinician

EDITORIAL There has been has been a change in the

editorial team since the publication of our June issue. Rodger Kempsford, who has been an active member of the editorial team from the beginning, has taken up a new appointment and for logistical reasons has relinquished his voluntary post as co-editor. We would like to thank Rodger for all his help and wish him success in his new career.

As readers might have nodced, the June issue of the Bulletin was circulated later than planned. This was the result of our printers not living up to their name and taking a long dme to complete their job. In fact, possibly due to the weight of our complaints, they have now closed down. This is the first issue with our new printers so we will see how it goes.

Although members of the Society continue to support the BSCR Bulletin by supplying articles on request we still remain underwhelmed by the amount of unsolicited material we receive. The BSCR Bulletin is supposed to be a forum for communication between members. We would like to hear from you.

For BSCR membership application, contact: Dr Anne-Marie L. Seymour

BSCR Secretary Department of Biochemistry

Oxford University South Parks Road Oxford 0X1 3QU

Telephone: 0865-275289

The Treasurer's address has changed to: Dr Allan S. Manning

BSCR Treasurer Sanofi Recherche Avenue de Bejar 1

1120 Brussels Belgium

LETTER FROM THE SECRETARY Dear Colleague, This quarter's BSCR Bulletin contains a ballot paper on the much discussed issue of pubHcation. I urge you to read it through and to reply as soon as possible. Whether to publish or not to publish has been a quesdon circulating in the Society for some years. It has generated much discussion at AGMs and in letters to the Bulletin. Originally, it was the poUcy of the Cardiac Muscle Research Group (and subsequently, the British Society for Cardiovascular Research) not to print or publish any proceedings from the major meetings in order to maintain a forum for preliminary and speculative work. However, there is now a significant body of opinion within the Society in favour of some form of publication of material presented at the Spring and Autumn meetings. Many of you will remember that, two years ago, the Society held an opinion poll to sound out whether the membership wanted to explore the possibilities of publication. The result of the ballot (58% for, 42% against) indicated that the Society was keen to pursue what possibilities might exist. Since then, abstracts of poster presentations at the past Autumn and Spring meetings have been printed in the Bulletin.

The Committee of the Society has met on a number of occasions to discuss the publication issue in depth and feel that they would like to make a number of recommendations to the membership. Since this is an important issue, the Committee feels strongly that this is best done by balloting the membership. The ballot paper is enclosed in the Bulletin and I encourage you to return your form to me by 30th October 1989 so that the views of the Society are truly represented at the AGM at the Autumn meeting in Oxford.

As I mentioned in the last edition of the Bulletin, three members of the Committee will be retiring at the end of this year. In an attempt to make the electoral system as fair and as democratic as possible, can I have nominations of candidates with the names of proposer and seconder and a brief curriculum vitae of the candidate by 30th October 1989 at the very latest. A postal ballot will then be circulated in November with the elected candidates taking office on 1st January 1989.

Details of the forthcoming meetings are included in the Bulletin. However, people are still being reticent about workshops. Despite offers from two individuals, nothing tangible has been organised. Can I, therefore, appeal to all of you to consider running a workshop? It is a wothwhile and stimulating forum which can offer younger members of the Society a chance to present their data.

Finally, and importantly, please note that my telephone number has changed to 0865-275289.

Best wishes,

Anne-Marie L. Seymour

4 BSCR MEETING ANNOUNCEMENTS

Autumn Meeting: 24th November 1989 CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY AND FAILURE

Venue: Academic Centre, John Radcliffe Hospital, Oxford

9.45-12.45 am B. Swynghedauw H. Taegtmeyer A-M. Seymour P. Sugden

12.45-2.00pm 2.00 - 6.00 pm

S. Houser G. Vassort C. Fry G. Cooper IV H. ter Keurs

6.00 - 6.30 pm 730

Biochemical Adaptations in Hypertrophy and Failure (Chairman: Professor G. K. Radda) Growth signals in cardiac overload Metabolic adaptation in hypertrophy and hypertension Models of hyperu-ophy and the role of phospholipids Protein synthesis in hyperttophy and failure Lunch in the Academic Centre

Electrophysiological Changes in Hypertrophy and Failure (Chairman: Dr G. Hart) Membrane current changes in hypertrophy Calcium current, adrenoceptors and hypertrophy Cardiac hypertrophy in the human heart The mechanical signal for cardiac hypertrophy induction Hypertrophy and the sarcoplasmic reticulum A.G.M. Dinner at Studley Priory

There will be a one hour poster session during the afternoon and the number of posters presented will be limited by the available space. This meeting is being sponsored by E.R. SQUIBB & SONS LTD.

Spring Meeting: 28-29th March 1990 BLOOD BORNE FACTORS IN MYOCARDIAL ISCHAEMIA

Venue: University of Liverpool Provisional Programme - Speakers and Topics

K.M. MuUane F.M. Williams C D . Nicholson C. Thiemermann

Leucocytes Neutrophils! complement Blood rheology Endothelin

A.J. Higgins C. L. Wainwright D. J. Longridge S.J. Coker

Neutrophil! endotheliuminteractions Platelets Thrombolysis 5-HT

Invitations have also been extended to cover the following topics: EDRF, lipids, fibrinogen/platelets and clinical thrombolysis. A few short (lOmin) oral communications will be presented and space is available for a number of posters. Abstracts on any topic will be welcome at this meeting. Those on subjects relevant to the theme of the meeting will be included as oral communications if time permits and the authors wish to present their work in this manner. Abstracts on other topics will be included in the poster session.

The meeting will commence after lunch on Wednesday 28th and finish around 5.00 pm on Thursday 29th March. Accommodation will be available in the Halls of Residence (Carnatic site), about 3 miles from the University. Parking space will be available at both the University and the Halls and transport will be provided between the two sites. The University is about a 10 min walk from Lime S treet Station. A Society Dinner will be held in Camatic House on Wednesday 28th March.

A full programme, abstract submission forms, registration forms and further details will be sent out with the December issue of the Bulletin. Anyonerequiringfurtherinformation now,orintending to submilanabstractshould contact:

Dr S.J. Coker Department of Pharmacology and Therapeutics

University of Liverpool P.O. Box 147

Liverpool L69 3BX Telephone; 051-794 5550

5

I.S.H.R. MEETING REPORT

lOth European Section Meeting 6-lOth September 1989

Rotterdam This meeting took place over three days

and was attended by an audience of around 300. The layout of the symposium consisted of two parallel sessions in which invited speakers gave didactic lectures around six themes, ranging from cardiac hypertrophy to purine/nucleotide metabolism. Equal emphasis was placed on the discussion of poster presentations (14 topics) and the associated abstracts were published (/ Mol Cell Cardiol [m9],2h suppl. IV). Bearing in mind the coming changes in the European Community, an additional symposium was organised to discuss European Heart Research into the next decade and involved specialists from various disciplines giving their views on funding of cardiac research in the nineties.

The first session dealt with the current understanding of cardiac hypertrophy in relation to changes in membrane proteins, tolerance to ischaemia and heart failure. B. Swynghedauw (Paris) summarised changes in both the population and density of specific membrane proteins associated with the onset of hypertrophy and the growth factors able to take account of these processes, for example oncogene products and heat shock proteins. P. Cummins (Birmingham) described the transitions in myofibrillar isoforms, particularly myosin, and how they may be related to compensatory changes in the physiological function of the hypertrophied myocardium. Complimentary to this, a review of the factors involved in both compensatory and end-stage hypertrophy was given by G.J. van der Vusse (Maastricht). Finally, H.G. Zimmer (Munich) described the relationship between hypertrophy and heart failure, and detailed the beneficial effects of pre-perfusion with ribose on

post-ischaemic reperfusion damage. Further sessions included lectures on the

pathophysiology of the Ca** channel. M. Lazdunski (Nice) provided an excellent in depth review of the criteria involved in the classification of Ca** channels and suggested that there may be as many as seven types, some of which have no pharmacological definition. P.A. Poole-Wilson (London) then went on to describe the role of Ca""" fluxes in ischaemia and reviewed the technical problems associated with the measurement of intracellular Ca"""̂ and how these have made the interpretation of data at the instance of myocardial damage difficult. To round off the session, W.G. Nayler (Heidelberg, Victoria) reviewed Ca*"̂ overload and cardiac necrosis, followed by L.H. Opie (Cape Town) who summed up the recent advances in instrumenting cardioplegia, especially in relation to the use of adenosine to induce hyperpolarisation and inhibition of the sinus pacemaker.

One of the final sessions assessed the impact of new techniques on the study of molecular and cellular cardiology. This began with G.K. Radda (Oxford), who gave an excellent review of the principles of n.m.r. spectroscopy and imaging, and the advances made in the clinical application of this technique to the study of human heart disease. The more recent use of positron emitting isotopically labelled compounds in the study of cardiac metabolism was described by W. Wyns (Brussels). This was followed by an in depth account of the role of e.s.r. in the detection of free radical production in the isolated perfused heart by J.L. Zweier (Baltimore) and the ability of this technique to measure the concentration of intracellular free oxygen. Finally, G. Elzinga (Amsterdam) described the technical advances made in the measurement of heat production in isolated superfused trabeculae.

Overall the meeting was a great success and of the highest standard. My thanks go to Jan Willem de Jong and his colleagues for organising a memorable and highly informative symposium.

John F. Unite Department of Biochemistry Oxford University

6

THE RESEARCH DEFENCE SOCIETY Accompanying this

article is a leaflet from the Research Defence Society

medical progress (RDS ) which outlines the aims for and activities of the Society,

man and animals The R D S was founded in 1908 to "make generally known the facts about experimental research involving the use of animals, the immense importance of such experiments to the advancement of knowledge, the welfare of mankind and the great saving of human and animal life, and the health due to them".

How has the RDS fulfilled this function? In the past this has been by producing

leaflets, booklets and more recently videos for those interested parties, schoolchildren and university students. It is becoming increasingly obvious in our VDU-saturated society that live speakers are much more effective. There is daily monitoring of anti-vivisection propaganda in newspapers and magazines throughout the UK. One of the most pressing needs is to counteract the damaging effect of this animal rights propaganda on the general public's views about the use of animals in medical research. Thus one of the current developments of the RDS is to work more closely with journalists to ensure that media coverage of medical research is given a more balanced view. It is, of course, very dificult to explain scientific merits to a lay audience.

Another approach to the problem is via the education system. Much of the effort of groups such as the British Union for the Abolition of Vivisection (BUAV), the National Anti-vivisection Society (NAVS), Animal Aid and the Dr Hawden Trust is aimed at young people at school (all levels) and university. Thus at an early age, children are subjected to disinformation about biomedical research. Later on they become exposed to more professional campaigns, emotive arguments and illogical conclusions as have been used before, but presented in a much more highly polished manner.

Can the RDS help? Those in cardiovascular research may feel

themselves particularly vulnerable as there is a tendency for the percentage use of animals to be greater within this field. There has always been

support for the possibility of alternative procedures that would decrease that neccesity. The advent of isolated myocyte cultures in addition to the sophisticated isolated organ perfusion techniques has helped to elucidate many aspects of cardiac electrophysiology, pharmacological reactions and interactions, mechanisms of myocardial ischaemia, to mention but a few.

However, within cardiovascular research there is still a fundamental need to investigate facts in the intact animal, so that knowledge of the interaction between the bodily systems is gained. An example might be drawn with the advent of thrombolysis. The theory of dissolving or removal of the clot in the coronary arteries has been brought into practice with the advent of streptokinase, TPA and angioplasty. The human clinical trials currently underway are based on the acquired data from many animal experiments; a fact that the newspapers conveniently forgot when announcing the miracle, single-shot cure for heart attacks. The use of large animal species was necessary for the development and understanding of the technique, as well as investigation of the possible effect of reperfusion damage. The majority of this work will remain unacknowledged in the popular press. Indeed, some researchers, particularly those with young families, may feel that this is the way that they would like it to be after the Blakemore episode. Colin Blakemore, the Waynflete Professor of Physiology at Oxford, had the courage to speak openly about the necessity for using animals in research. Since then he has been singled out for special attention by the animal rights movement. He has received hundreds of threatening, abusive letters and telephone calls, as well as the appearance of false stories in the media despite a Press Council ruling. Thus, as well as supplying advice to individuals on how to handle anti-vivisection propaganda, the RDS has decided to establish a special fund to enable scientists to obtain proper legal advice on how to deal with libellous or slanderous attacks and, if appropriate, to take legal action.

The activities of the Animal Liberation Front (ALF), e.g. the bombing at Bristol University and the acid attack on security guards

7

at Guy's, are so obviously outrageous that they are probably counterproductive to their cause. Nevertheless, it brings to light the need for vigilance and security by research workers. Vigilance is not expensive but time consuming, security can be both. The financial aspect is a great problem in the current restrained financial climate of the universities and colleges. Resources are already stretched in those establishments which have to modernise their existing animal accommodation and increase administration to meet the requirements of the Animal (Scientific Procedures) Act 1986. Centralised use of animal facilities is not always possible because of individual researchers' special requirements, and the restraints of older styles of architecture.

Apart from following their own research work, many scientists are faced with the problem of having to cope with the negative attitudes of some staff and students towards courses that require animal use. Lecturers have found that caution needs to be exercised in the material presented in lectures. These attitudes have undoubtedly been inculcated by anti-vivisectionist propaganda from an early age. A regrettable consequence of this might be that those departments who use animals might be those to be closed in the current wave of cutbacks.

The future Over the last five years the animal rights

campaigners have changed their tactics in a disturbing manner. They employ cleverly designed and professionally marketed campaigns against the use of animals in medical research. The RDS takes the view that the best way to counteract this campaign of mis-information is with a corresponding campaign of correct information. The RDS will work towards this objective, but it will need the support of members for it to become a reality.

If you would like to join the RDS, a membership leaflet has been included with the BSCR Bulletin. Further copies of this leaflet and infomiation can be obtained from the RDS, Grosvenor Gardens House, Grosvenor Gardens, London SWIW OBS.

Angela Drake-Holland RDS Associate Director

BOOK REVIEW Atlas of Congenital Cardiac Surgery

Surgical Practice Illustrated-2 Paul E. Ebert

Illustrated by Leon Schlossberg (£85.00, Churchill Livingstone)

This book is an excellent introduction to the trainee surgeon in this speciality. The information provided will not only clarify the way ahead for the enthusiastic first assistant but should also serve to refresh the senior surgeon through the steps of less frequently undertaken procedures.

It is a daunting task to portray the complex three dimensional structures in the congenitally malformed heart. Leon Schlossberg achieves this with the hand of a true master and supplements his illustrations with the occasional diagram in the more intricate situations as in atrioventricular canal and the Senning operation. The area of particular interest is highlighted and the rest of the operative field is depicted in less contrasting tones, giving an unobtrusive but accurate record of cannulae, slings and clamps, details the surgeon is constantly aware of. What seemed like a baffling arrangement of chambers, defects and vessels becomes a lesion-complex correctable via a clearly defined strategy. The illustrations are of the highest quality and are all drawn to a characteristic style, a feature annoyingly absent in many other atlases.

The general layout of the book is also consistent and this facilitates usage of the text and reference to a particular operation. Paul Ebert's notes are clear and succinct. They serve to orientate the surgeon and then take him or her step by step through the procedure. Personal preferences are expressed and hints of surgical technique are given. That surgery is an art is never forgotten and the apprentice in this field is encouraged to make his own choice.

This is not a reference atias to be shelved and consulted when the need arises, it is a book that is absorbing from beginning to end.

A, Manche St. Bartholomew's Hospital

Sanofi Research Centre CARDIOVASCULAR SCIENTIST

A cardiovascular physiologist/pharmacologist is required to provide scientific leadership to a team of 4-6 research scientists and technicians engaged in the discovery and development of novel agents for the treatment of ischaemic heart disease and related disorders. The appointed person will possess an in-depth background knowledge of the assessment of haemodynamic and/or electrophysiological measurements in chronic or acute models of cardiovascular disease states, together with a Ph.D. and some postdoctoral experience either within the pharmaceudcal industry or at an academic centre of excellence. A knowledge of the French language is desirable.

SANOFI is a major pharmaceutical company involved in research and development in pharmaceudcal, veterinary and agricultural activities. It has major research centres in many parts of Europe including Brussels, Milan, Montpellier, Toulouse and Paris.

The Research Center of S ANOFI-LABAZ is situated on the outskirts of Brussels in an attractive part of Europe and offers superbly equipped new laboratories. This position offers a comprehensive salary and benefits package.

Please write, enclosing a full curriculum vitae, to:

Mr Bils (The Personnel Officer) SANOFI RESEARCH CENTER

I, Avenue de Bejar 1120 Brussels BELGIUM

The Johns Hopkins Hospital POSTDOCTORAL FELLOWSHIP

Postdoctoral fellowship available immediately to study the relationship between cardiac metabolism and physiology using in vivo NMR spectroscopy. Research will be directed towards an understanding of chronic adriamycin cardiotoxicity. Experience in cardiac physiology and/or metabolism preferred. Knowledge of NMR spectroscopy and imaging techniques desirable but not essential.

Send curriculum vitae and two or more letters of recommendation to:

Dr J.D. Glickson Department of Radiology

Division of NMR Research The Johns Hopkins Hospital

MRI Room 110 600 N. Wolfe Street

Baltimore MD 21205

U.S.A.