When I was asked some years ago by the editors of the Handbook of Experimental Pharmacology to edit a new volume on Antianginal Drugs, I agreed on the condition that, in accordance with my scientific background, primary emphasis be given to clinical pharmacology and therapeutics. It soon turned out that, due to rapid developments in this field, nothing of the previous volume on Antianginal Drugs by Charlier (Vol. 31, 1971) could be retained apart from its basic idea of devoting considerable space to methodology. Since editors must operate within certain limits, I had to abstain from dealing with acute myocardial infarction in detail despite the well-known overlap between unstable angina, the preinfarction syndrome, and acute myocardial infarction. It was only possible for acute myocardial infarction and the concept of reduction of infarct size to be briefly discussed within the chapter on pathophysiology of acute coronary insufficiency. The chapter on invasive methods provided an opportunity to touch on new approaches to early intervention in acute myocardial infarction. Here, intracoronary streptokinase therapy and PTCA are considered, again with attention to the overlap between mechanical and pharmacological interventions.

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General Principles.- 1 Epidemiology of Ischemic Heart Disease With 5 Figures.- A. Preface.- B. Multiple Risk Factor Intervention Trial.- I. Methods, Eligibility, Intervention Strategies, Randomization.- II. Results and Interpretations.- III. Comments.- IV. Multiple Risk Factor Intervention in North Karelia.- V. The WHO European Collaborative Trial.- VI. The Oslo Trial (Primary Prevention).- C. Epidemiologic Observations Confirming the Trend of Decreasing Coronary Mortality in the United States.- I. Food Consumption Pattern: United States and Germany.- II. Development in England.- III. Life Expectancy in the United States.- IV. Life-Style Changes Versus Improved Medical-Surgical Care.- V. The Rochester Study.- VI. The Minneapolis Study.- VII. The Chicago Peoples Gas Company Study.- VIII. Pathologic-Anatomic Proof that Coronary Atherosclerosis is Decreasing.- D. Hypertension and Hypercholesterolemia: Unifactorial Intervention for the Prevention of Ischemic Heart Disease.- I. Prevention of Fatal and Nonfatal Ischemic Heart Disease Through Unifactorial Intensive Drug Therapy of Hypertension.- II. Results.- III. Prevention of Myocardial Infarction Through Unifactorial Treatment of Hypercholesterolemia.- IV. Summary.- E. Cigarette Smoking and Obesity: Unifactorial Intervention.- I. Smoking.- II. Obesity.- References.- 2 Pathophysiology of Coronary Circulation and of Acute Coronary Insufficiency With 11 Figures.- A. Regulation of Coronary Blood Flow.- I. Overview.- II. Metabolic Autoregulation and the Adenosine Hypothesis.- III. Alternative Hypotheses Explaining Metabolic Autoregulation.- B. Coronary Artery Stenosis and Spasm.- I. Overview.- II. Influence of a Coronary Stenosis on Myocardial Perfusion.- C. Influence of Underperfusion on the Myocardium.- I. Influence on Substrate Metabolism.- II. Influence on High Energy Phosphates.- III. Regional Contractility and Nucleotides in Reperfused Myocardium.- IV. Effect of Regional Ischemia on Local Myocardial Function.- D. Myocardial Infarction.- I. Mechanisms Leading to Cell Death.- II. Reduction of Infarct Size as a Therapeutic Goal.- References.- 3 Pharmacodynamic Principles of Action of Antianginal Drugs.- A. Introduction.- B. The Principles of "Unloading" the Heart.- C. Groups of "Unloading Substances".- D. The Vasospastic Concept.- E. Concepts Underlying Inhibition of Platelet Aggregation.- F. Conclusion.- I. The Augmentation of Oxygen and Substrate Supply to the Heart.- II. Reduction of Myocardial Oxygen Demand: Improvement in the Economy of Cardiac Performance.- Test Methods.- 4 Experimental Testing of Antianginal Drugs in Animals.- A. General Considerations.- B. Measurement of Relevant Parameters.- I. Myocardial Blood Flow.- II. Myocardial Metabolism.- III. Myocardial Function.- IV. Electrocardiogram.- V. Signal Transmission.- C. Experimental Models.- I. Isolated Perfused Hearts.- II. Myocardial Underperfusion and Angina Pectoris.- III. Myocardial Infarction.- IV. Collateral Circulation.- V. Reperfusion and Retroperfusion.- D. Summary.- References.- 5 Noninvasive Methods: Systolic Time Intervals and Echocardiography With 2 Figures.- A. Introduction.- B. Systolic Time Intervals.- I. Measurement of Systolic Time Intervals.- II. General Points.- III. Determinants of the Systolic Time Intervals.- IV. Validation of Systolic Time Intervals.- V. Use of Systolic Time Intervals to Study Drug Action with Antianginal Preparations.- VI. Place of Systolic Time Intervals in Clinical Pharmacology.- C. The Use of M-Mode Echocardiography in Assessing Antianginal Drugs.- I. Technique of Recording.- II. Technique of Measurement.- III. Reproducibility of Dimension Measurements.- IV. Derived Quantities.- V. Computed Quantities.- VI. Effect of Physiological Manoeuvres.- VII. Effects of Drugs.- D. Conclusions.- 6 Peripheral Circulation With 6 Figures.- A. Assessment of Antianginal Drugs Through Studies of the Peripheral Circulation.- B. The Use of Human Subjects for Studies on the Peripheral Circulation.- I. Anatomical Considerations.- II. Ethical Considerations.- C. Administration of the Test Drug.- I. Oral Administration.- II. Intravenous Administration.- III. Intra-arterial Administration.- IV. Percutaneous Administration.- D. Measurement of Blood Flow in the Peripheral Circulation.- I. Venous Occlusion Plethysmography.- II. Strain-Gauge Plethysmography.- III. Thermal Methods.- IV. Pulse Volume Methods.- V. Isotope Clearance Methods.- VI. Differentiation Between Skin and Muscle Blood Flow.- VII. Ultrasonic Flow Meters.- E. Measurement of Venous Tone.- I. Volume Measurement at Constant Pressure.- II. Pressure Measurement at Constant Volume.- III. Vein Diameter Measurement.- F. Measurement of Vascular Permeability.- References.- 7 Exercise Testing With 3 Figures.- A. Introduction.- B. Value of Stress Testing in Asymptomatic Subjects.- C. Value of Stress Testing in Epidemiology.- D. Indications for Exercise Testing.- E. Safety of Stress Testing.- I. Arrhythmias.- II. Hypotension.- F. The Use of Stress Testing in the Evaluation of Therapy in Patients with Ischaemic Heart Diseases.- G. Gardiac Response to Exercise.- H. ECG Response to Exercise.- J. Evaluation of the Effects of Therapy.- I. Nitrates.- II. ?-Adrenergic Blocking Drugs.- III. Calcium Channel Blocking Drugs.- K. Training.- L. Summary.- References.- 8 Radionuclide Methods With 17 Figures.- A. Clinical and Pathophysiologic Aspects of Testing Antiangial Drugs with Radionuclides.- B. Some Important Definitions in Nuclear Medicine.- C. Fundamentals of Nuclear Cardiology.- I. Radionuclide Procedures for Imaging of Myocardial Perfusion..- II. Radionuclide Procedures for Imaging of Myocardial Metabolism.- III. Failures of Myocardial Function.- IV. Failures of the Conduction System of the Heart and Techniques for Their Imaging.- D. Application of Radionuclides for Testing Antianginal Drugs.- I. ?-Blockers.- II. Vasodilators.- References.- 9 Assessment of Coronary Artery Disease and Myocardial Ischemia by Invasive Methods With 18 Figures.- A. Parameters for the Assessment of Cardiac Function in Ischemic Heart Disease.- I. Introduction.- II. Technical Aspects.- III. Hemodynamic Monitoring.- IV. Parameters to Evaluate Cardiac Loading Condition.- B. Assessment of Functional Significance of Coronary Artery Disease..- I. Indications for Coronary Arteriography.- II. Information Gained from Coronary Angiography.- III. Techniques of Coronary Arteriography.- IV. Risks and Complications.- C. Quantitative Approach to Coronary Artery Disease by Invasive Methods.- I. Introduction.- II. Assessment of Left Ventricular Function.- III. Assessment of Coronary Artery Morphology.- IV. Coronary Artery Spasm.- V. Cardiac Metabolism in Ischemia.- D. 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