An International Symposium "Catecholamines and the Heart" was held in Munich in May 1981, which was organized in cooperation with the Council on Cardiac Metabolism of the International Society and Federation of Cardiology and with the Microcirculation Working Group of the European Society of Cardiology. It was the aim of the organizers to evaluate in this Symposium the recent advances made in the field of sympathetic control of heart function. Particular attention was given to neural sympathetic pathways, to mechanisms and consequences of adrenoceptor stimulation and blockade as well as to clinically relevant implications mainly regarding the significance of catecholamines and of adrenoceptors in various heart diseases. The broad scope was covered in 34 papers presented by physiologists, pharmacologists and cardiologists during a two day meeting which was attended by an international audience. This book includes all papers as well as the discussions following each presentation. To accomplish rapid publication the manuscripts are published as submitted by the authors. The discussions were edited making use of the written questions and answers of the discussants. The Symposium was generously sponsored by Astra Chemicals GmbH, Wedell Holstein, Germany, which thus made possible a very fruitful exchange of information, ideas and concepts between specialists in various disciplines. The organizers gratefully acknowledge this support once again and would like to thank Dr. T. Kreuzer, the representative of Astra Chemicals, for his personal engagement.

Microcirculation is a rather new field which has been of predominant interest to basic scientists, linking togeth~r technical, hemodynamic, and biochemical aspects. The fmdings elaborated, however, are not only of theoretical interest, but bear in addition great clinical implications. In clinical cardiology this became quite evident by the use of tracers in order to study myocardial perfuSion and by the deSCription of certain clinical entities - such as angina with normal coro nary arteries - which are best explained by "disturbed microcirculation". With respect to this new developing theoretical and clinical field of cardiac microcirculation it was the aim of the Microcirculation Working Group of the European Society of Cardiology to have a symposium on which all different but clinically relevant aspects of cardiac microcirculation will be covered. This symposium, held in Heidelberg in January 1980, was planned not only for the exchange of concepts and ideas, but was expected to be in addition partially a teaching session; the basic scientists should be directed toward a better under standing of the clinical problems, and the clinicians should learn more about the basic mechanisms regulating substrate and ion exchange in such an impor tant organ as the heart, and furthermore the theoretical limitations of some of the diagnostic and therapeutical procedures should be taught. Without a lot of help we would never have succeeded in organizing the sym posium and editing its results.

This is a little book with no great pretensions. The authors do not claim it to be world-startling nor Nobel- or Pulitzer-prize-winning. It is a valuable primer for pharmacokinetics for those desiring a proper initiation into previously assumed mysteries. It is fully intended as an introduction to the basic concept of pharmacokinetics and will be welcomed by all who wish to apply its principles to their own disciplines, whether in life sciences or medicine, without being confused by excess mathematics. It is edited by two well-known German scientists who are primarily practicing pediatricians and who use pharmacokinetics in their daily work, in a field of medicine where the proper adjustment of doses for infants and children is a delicate and life-preserving art. They were trained as pediatricians and as pharmacokinetists by the world-renowned Profes sor F. HARTMUT DOST, who uniquely synthesized these two disciplines and who, as a pioneer in this field, published the first book on pharmacokine tics in 1953. In their own right, the editors have conducted excellent and unique research on the effect and fate of drugs and have followed up the unexpected changes in drug action accompanying the rapid developments encountered in the initial hours, days, and weeks after birth. You will find some interesting Germanisms in this book a la Professor DOST. I personally feel that these will give some spice to their renditions.

Dieses Buch bietet eine exzellente Zusammenfassung des Standes der Forschung und deren klinische Anwendung zu Beta-Blockern. Der Einsatz von Beta-Blockern bei verschiedenen koronaren Erkrankungen wird ausfuhrlich beschrieben. Grenzen und Abgrenzungen zu anderen Therapiemoglichkeiten werden diskutiert."

2. Elimination . . . . . . . . . 102 a) Krankhafte Veranderungen des eliminierenden Organs 102 b) Altersabhangige Veranderungen der Elimination . . . 104 c) Pharmakogenetische Faktoren. . . . . . . . . . . 105 d) Abhangigkeit der Eliminationsgeschwindigkeit vom Saure-Basen- Haushalt . . . . . . . . . . . . . . . . . . . 106 e) Cicadiane Rhythmik der Eliminationsgeschwindigkeit . 108 f) Wasserdiurese und Eliminationsgeschwindigkeit 108 g) Loesungsmittelmangel . . . . . . . . . . . . . . 108 h) Enzyminduktion . . . . . . . . . . . . . . . . 109 i) Hemmung der Elimination durch toxische Wirkung. 113 cx) Verdrangung aus der Eiweissbindung . . . . . . 113 ss) Clearancedepression . . . . . . . . . . . . . 114 y) Beschleunigung der Elimination durch enteral verabreichte Komplexbildner und Adsorbentien 114 3. Verteilungsvolumen . . . . . . 115 a) Dehydratation - Hydratation 115 b) Hydropische Zustande 116 4. Schlussbemerkung . . . . . . 116 IX. Verwendung von Analog-Rechnern in der Pharmakokinetik . 118 1. Einfuhrung . . . . . . . . . . . . . 118 2. Arbeitsprinzip des Analogrechners. . . . 119 3. Die Programmierung des Analogrechners . 122 4. Anwendung . . . . . . . . . . . . . 124 x. Praktische Anwendung pharmakokinetischer Verfahren . . . . . . . . 130 (Von W. -H. Wagner) 1. Einleitung. . . . . . 130 2. Messverfahren . . . . 130 130 a) Mikrobiologische Methode 131 b) Chemisch-analytische Methode. c) Nachweis mittels radioaktiv markierter Substanz 131 3. Bewertung der Ergebnisse von Tierversuchen . . . 132 4. Gewinnung pharmakokinetischer Groessen und Konstanten . 133 a) Bestimmung aus der graphischen Darstellung . . . . 133 b) Verwendung programmierter Verfahren. . . . . . . . 133 5. Mathematische Grundlagen der programmierten Verfahren. 134 XI a) Verteilung einer Substanz in mehreren Kompartimenten. 134 b) Blutspiegelverlaufe bei reiner Invasion. . . . . . . . . 135 c) Blutspiegelverlaufe bei reiner Elimination . . . . . . . 137 d) Blutspiegelverlaufe bei gleichzeitiger Invasion und Elimination (Bateman-Funktion) . . 137 e) Kumulation, Grenzkurve 142 f) Dosierungsschema 142 6. Auswertungsbeispiele . 143 Weiterfuhrende Literatur. 154 Sachverzeichnis . . . .