The nitrates have remarkable clinical effects that have stood the test of time in the management of ischemic heart disease. What is unusual about this class of com pounds is that, after many years of clinical use, we are still exploring new avenues as to the vascular mechanisms of their effect, their applications in treating other clini cal conditions, and the development of products with more favorable pharmacoki netic properties. This volume represents the proceedings of a symposium held June 14-16, 1984, in Montreux. The papers were selected to explore the current state of knowledge re garding the mechanisms of action, pharmacokinetics, and clinical efficacy of ni trates. Particular attention has been given to newer studies utilizing the 5-mononi trate metabolite of isosorbide dinitrate, a drug whose pharmacokinetic properties may make it an important new agent in the treatment of angina and congestive heart failure. One of the benefits of an international meeting of experts sharing their views on an internationally used group of drugs is that differences in concepts and clinical practice become apparent and can be discussed. The Montreux forum made it clear that clinicians in North and South America and Europe have diverging views on how the nitrates should be used.

Preface

Introductory Remarks on the Development of Isosorbide-5-Mononitrate
Vasodilation with Nitrates
Nitrates: Mechanism of Vasodilation
Effect of Different Vasodilators on Epicardial Coronary Arteries
Effects of Isosorbide-5-Mononitrate on Hemodynamic Parameters and on Regional Myocardial Ischemia in Conscious Dogs
Isosorbide-5-Mononitrate Increases Cyclic Guanosine Monophosphate Concentration in Rat Aorta in Vitro and in Vivo
Activation of Counter-Regulatory Mechanisms on Administration of Equipotent Doses of Different Types of Vasodilators to Conscious Dogs
Differences in the Metabolism of Isosorbide-5-Mononitrate and Isosorbide Dinitrate and Their Consequences for Toxicologic Findings
Clinical Pharmacology
Pharmacokinetics of ISDN, Sustained-Release ISDN, and IS-5-MN
Vascular Pharmacokinetics of Nitrates
Effect of Glyceryl Trinitrate, Isosorbide-5-Mononitrate, and Propranolol on Apparent Liver Blood Flow
Kinetics of IS-5-MN and Its Glucuronide in Patients with Renal Failure
Pharmacokinetics of IS-5-MN after Oral and Intravenous Administration in Patients with Hepatic Failure
Tolerance to Nitrates
Nitrate Tolerance: Animal Experiments And Clinical Studies in Heart Failure
Development and Disappearance of Tolerance to Organic Nitrates in Conscious Dogs
Tolerance and Rebound Phenomena in Nitrate Therapy
Tolerance to the Antiischemic Effect of Isosorbide Dinitrate during Continuous but not during Intermittent Oral Therapy
Clinical Relevance of Nitrate Tolerance
A Double-Blind Cross-Over Study on the Effectiveness and Possible Development of Tolerance during Long-Term Therapy with Isosorbide-5-Mononitrate or Isosorbide Dinitrate Slow-Release in Coronary Artery Disease
Nitrate Tolerance in Angina Pectoris
Comparison of the Hemodynamic Effects of Various Doses of Isosorbide-5-Mononitrate Following Single-Dose and Long-Term Administration in Patients with Coronary Heart Disease
Slow-Release IS-5-MN for the Treatment of Angina Pectoris: Duration of Effects
Nitrates in Coronary Insufficiency
The Mechanism of Nitrates in the Relief of Rest Angina
Beneficial Effects of Isosorbide-5-Mononitrate on Exercise Performance in Patients with Chronic Stable Angina Pectoris
Comparison of Changes on Exercise-Induced Ischemia After a Single Oral Dose of IS-5-MN and ISDN
Double-Blind, Randomized Cross-Over Study on the Coronary Therapeutic Efficacy and Tolerance of IS-5-MN (ISMO 20) in Comparison with IS-5-MN + Metipranolol (ISMO-DISORAT 20/5) and Placebo
The Efficacy of IS-5-MN in Patients with Ischemic Heart Disease: A Pilot Study
Efficacy of Isosorbide-5-Mononitrate in the Prevention of Induced Attacks of Vasospastic Angina: Preliminary Results
Double-Blind Comparison of the Effects of Nifedipine and Isosorbide-5-Mononitrate on the Circulatory Response to Exercise, Exercise Tolerance, and ST-Segment Depression in Patients with Ischemic Heart Disease
Clinical Importance of the Coronary Steal Phenomenon: Are the Coronary Steal Phenomenon after Dipyridamole and the Antianginal Efficacy of Isosorbide Dinitrate of Nifedipine Related to Coronary Anatomy?
Effect of Nitroglycerin Patches on Hemodynamic and Exercise Parameters in Patients with Coronary Artery Disease Compared with IS-5-MN and Placebo
Double-Blind, Cross-Over Study on the Antianginal Efficacy of IS-5-MN and ISDN s.r., a Multicenter Trial
Hemodynamic Effects of Isosorbide-5-Mononitrate in Patients with Coronary Artery Disease, at Rest and Under Exercise
The Effects of Isosorbide-5-Mononitrate on Left Ventricular FunctionAssessed by Systolic Time Intervals
Assessment of Changes in Left Ventricular Performance Induced by Nitrates at Rest Using an ECG-Gated Scintillation Probe Device
Nitrates in Heart Failure
Nitrate Therapy of Congestive Heart Failure
Efficacy of IS-5-MN (ISMO 20) in Patients with Coronary Artery Disease and Impaired Left-Ventricular Function
Hemodynamic Effects of IS-5-MN in Patients with Congestive Heart Failure.