International Boehringer Mannheim Symposia – serie

H. RoSKAMM This International Symposium to be held on the occasion of the third anniversary of our institution and under the auspices of the European Society of Cardiology is entitled "Ventricular Function at Rest and During Exercise". We have chosen the general term "ventricular function", because we want to include the different aspects of myocardial function like contrac­ tility, relaxation and compliance and their influence upon the overall pumping function of the heart. Heart failure at rest is a rather advanced outcome of a continuous spectrum of function disturbances. In order to grade these, it is reasonable to differentiate between pump function of the heart as a whole and muscle function of the myocardium. Compen­ satory factors like hypertrophy or the Frank-Starling mechanism may maintain the overall pump function of the ventricle, despite a defect in the underlying myocardial contractility. The time sequence of the func­ tional disturbances may be as follows (Fig. 1): EXERCISE £""-----,--------------, >- " 5 ~, ~ ~, ~ '~ I o u f--~__;_;IJ"_'_~'"'"* t REST II Fig. 1. Schematic presen­ REDUCTION OF CON REDUCTION OF CON PUMP FAILURE tation of time sequence of TRACTILITY RESERVE TRACTllITY . or REST progression in deteriortation _ TIME of ventricular function xvn The lower line represents contractility at rest, the upper one contrac­ tility during maximum exercise; the range between these two lines can be called contractility reserve.

More than 10 years have passed since the memorable symposium on "Myocardial Contractility," edited by R. D. Tanz, F. Kavaler and J. Roberts (New York and London, Academic Press, 1967). PathogeneSis of myocardial failure still involves many questions. The latest scien­ tific findings on fundamentals of myocardial contraction encouraged us to organize this international symposium held in Rottach-Egern at Tegernsee (Germany), June 17 to 19, 1976 sponsored by the European Society of Cardio~ogy. It seemed appropriate to assemble prominent workers in this field in an attempt to correlate their respective in­ formation on cardiac function. In this connection it must be remembered that our present understand­ ing of the cardiovascular system and today's therapeutic and preventive measures are the fruits of yesterday's research. Further progress in this field will be conditioned by various circumstances: to win highly motivated creative people for clinical research, to mediate time and contacts for their learning new methods, and to provide adequate faci­ lities for scientific work in our hospitals. Therefore, the aim of the conference was to discuss those aspects of myocardial failure, that are believed to require further studies in the future by integrated efforts of research workers in several disciplines, especially to promote the pertinent exchange of ideas between basic and clinical research.

In spite of old vintage and 200 years of clinical use, digitalis remains an interesting therapeutic agent, to clinicians as well as to the pharmacologist, the biochemist, and colleagues in other diciplines of theoretic medicine. When a drug, however, has so many attractive facets, it seems proper and aJvis­ able for the success of a scientific meeting to focus on a number of well-defined aspects. This symposium was devoted to pharmacokinetics, drug metabolism, analytic procedures, blood level determinations, and their interpretation both for thera­ peutic and toxic situations. Considerable progress has been made during the last years in this area of digitalis research. The time was suitable for a critical reap­ praisal of facts and theories and for future planning. Our main intention was to relate analytic data and biochemical findings to clinical problems and questions. Despite the undoubtedly basic character of clinical pharmacology, it is neverthe­ less an applied science which should help to develop the rational basis of thera­ peutics. We are particularly grateful to the active participants who bore the burden of preparing presentations and - even worse - manuscripts. At the same time we are well-aware that many other active research groups would have been able to contribute in this way, but our program was limited because of the short time available. Their knowledge is included in the discussion parts of the meeting, so we hope a well-balanced description of the present state of affairs emerged in this volume.

Systolic time intervals (STI), known for a long time, were revived in the early 1960s by Arnold Weissler. The first important papers came from him; they eval- uated STI measurements in larger populations, established norms, and compared STI measurements with other invasive methods. Since then, several hundred ex- cellent papers have appeared using and evaluating STI measurements for myo- cardial function studies. These have appeared in prominent cardiologic journals throughout the world as well as in the anesthesiologic and pediatric medical literature. When consent of subjects to medical experimentation became a prominent and necessary issue, the noninvasiveness of investigative methods in medicine, wher- ever possible, resolved the issue. Noninvasive measurements of STI proved to be an excellent monitoring parameter of cardiac function during anesthesia, and anesthesiologists wished to learn more from the long experience of cardiologists with STI. An organizing committee of List, Gravenstein, and Spodick was accordingly formed. Invitations were issued for an international conference on STI.With more than 40 clinical researchers using STI, it was, of course, difficult to hear them all within two days. A generous sponsor, the AVL Company, Graz-Schaffhausen, made possible the International Conference at Graz. Publication of the proceedings of the Confer- ence became feasible with help from Boehringer-Mannheim.

This volume presents the proceedings of the Symposium on "Hypertension .* Mechanisms and Management" held at the "Akademie der Wissenschaften" in Mainz on the 1st and 2nd October, 1979. The Symposion has been dedicated to Professor Hanns-Peter Wolff, who has been the Chairman of the First De- partment ofIntemal Medicine at the University of Mainz since 1968, on the occasion of his 65th birthday. The conference was mainly devoted to pathophysiological aspects of high blood pressure. A first series of papers discussed the possible role of the sympathetic nervous system in the pathogenesis of arterial hypertension. Despite consider- able methodological progress made in the measurement of circulating catechol- amines it is still unclear whether catecholamines are raised in essential hyper- tension, and if so, whether this is important for the pathogenesis of high blood pressure. Practically all papers of the first session were related to this question. For several decades the renin-angiotensin system has been the central topic of any hypertension meeting. We thought that additional lectures or papers on this subject might fail to provide new aspects.We therefore asked five experts who have been working in this field for many years to discuss in a Round Table whether or not the renin-angiotensin system might playa significant role in human hypertension. A further topic were the renal tissue hormones other than renin-angiotensin. The papers discussed in particular kallikrein and its possible role in activating renin and thereby possibly contributing to high blood pressure.

Hypertensive heart disease is one of the most frequent diseases in man. It is esti­ mated that there are six to eight million hypertensive patients in the Federal Re­ public of Germany today. This corresponds with an incidence of 10%-15% in the whole population. Approximately between three and four million show organic eardiac manifestations of hypertension. Of all deaths occurring before the age of 65,30%-40% are attributable to hypertension, and the total morta­ lity from hypertension is about 20%-25%. Recent epidemiological and clini­ cal studies have revealed similar figures for other countries, such as the United States and Japan. Hypertensive hypertrophy and cardiac failure are found to be many times more frequent than eardiae hypertrophy and failure of any other origin. Despite the apparent clinical and social importance of the biologieal system "blood pressu­ re and the heart", data on eardiac performance, on systemic and coronary haemodynamics and on the morphological, bioehemical and contractile proper­ ti es of ventrieular heart muscle in both experimental and clinical hypertension are rare. This is the reason and stimulus for having organized this symposium, which is the first one coneeming this topie.

Primary myocardial disease, nowadays referred to as congestive or, more re­ cently, dilating cardiomyopathy, comprises disorders of varied etiology. Most oftenly the pathogenetic mechanism or causative agent remains unknown. The significance of inflammatory processes, i.e. myocarditis in a wider sense as the etiologic factor has been debated for many years. In a few instances, especially in children and newborns viral infections can be incriminated. In adults this etiology can be ascertained only in rare instances. And it has remained entirely uncertain if, or under which circumstances, and how often virus myocarditis can lead to a chronic disorder of the heart, namely dilated cardiomyopathy. Although it would seem conceivable that an immunological response to an infectious agent might induce parenchymal damage with subsequent loss of cellular function and structural integrity of permanent nature, i.e. dilatation, functional deterioration and dysrhythmias, numerous attempts to establish such a pathogenetic mechanism have not yet furnished convinicing results. Therefore the reader will direct his attention specifically to the respective contribution in this volume. Morphologic studies have yielded a host of new and intriguing findings in cardiomyopathy, but have likewise failed to settle the basic question as to which etiology can be held responsible in a given case, especially if an inflam­ matory process can be incriminated. Specific processes such as sarcoidosis of the heart undoubtedly furnish examples of chronic inflammation as a cause of dilating cardiomyopathy. This disorder, however, as a specific inflammato­ ry myocardial affection, i.e. myocarditis, is encountered only infrequently.

On behalf of the organizing committee of this symposium, I would like to wel­ come you to Cologne and thank you very much for coming. We appreciate that some of the leading scientists in the field of hypertension have accepted our invi­ tation to participate actively at this conference. Our first symposium on renin-angiotensin, aldosterone, and hypertension took place at Titisee in the Black Forest in 1967. The second one, on the renin-angio­ tensin-aldosterone system under the influence of therapeutic procedures, was held at the same place in 1970. Five years later in 1975 at a third symposium in Cologne, we discussed the problems of central nervous control of sodium balance in relation to the renin-angiotensin system. The symposium about to begin is devoted to the significance of mineralocorti­ coids in developing and sustaining arterial hypertension. 1) In order to provide a physiologic background for the understanding of the mechanisms involved in this complicated process, new concepts on the regulation of mineralocorticoid secretion must be discussed in detail. As the most important mineralocorticoid, aldosterone is regulated by changes in sodium and potassium homeostasis and is also influenced by adrenocorticotropic hormone (ACTH).