Contrast media are drugs by default. Had there been no default, there would be no need for a related pharmacology, and thus no need for this book. Radiographic contrast media (CM) are substances whose primary purpose is to enhance diagnostic information of medical imaging systems. The position of CM in pharmacology is unique. First, there is the unusual requirement of biological inertness. An ideal CM should be completely biologically inert, i.e., stable, not pharmacologically active, and efficiently and innocuously excretable. Because they fail to meet these requirements, CM must be considered drugs. The second unusual aspect of CM is that they are used in large quantities, their annual production being measured in tens of tons. It is not in spite of, but because of, the increased use of new radiographic systems, computed tomography, digital radiography, etc., that consumption is on the rise. And, it is not likely that the other emerging imaging modalities - NMR, ultrasonography, etc. - will displace radiographic CM soon; it is quite probable that these remarkable compounds will continue to play an active role in diagnostic imaging in the foreseeable future.

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Introduction: State of the Art and Design Principles of Contrast Media.- References.- 1 Chemistry of X-Ray Contrast Media.- A. Introduction and Scope.- B. Biological Requirements.- I. Physicochemical Properties.- 1. Water Solubility.- 2. Viscosity.- 3. Osmolality.- II. Chemical Stability.- III. Biological Safety.- C. Ionic Contrast Media.- I. Synthesis.- II. Evolution of Structural Types.- 1. Improving the Functional Groups.- 2. Reduction of Hypertonicity.- D. Nonionic Contrast Media.- I. Solubility Aspects of Nonionic Media.- II. Viscosity Considerations.- III. Osmolality.- IV. Stability.- 1. Deiodination.- 2. Instability of the Polyhydroxylalkyl Group.- 3. Hydrolysis of the Coupler Group.- V. Synthesis of Nonionic Compounds.- 1. Synthetic Approaches.- 2. Manufacturing Costs.- VI. Stereochemical Aspects of Contrast Media.- 1. Isomers Resulting from Restricted Rotation.- VII. High-Pressure Liquid Chromatography.- VIII. Water-Insoluble Nonionic Contrast Media.- 1. Oily Contrast Media.- 2. Benzoate Esters.- 3. Perfluoroalkyl Halides.- E. Oral Cholecystographic Agents.- References.- 2 Urographic Contrast Media and Methods of Investigative Uroradiology.- A. Introduction.- B. Historical Remarks.- C. Attenuation of X-Rays.- I. Contrast Medium Concentration in Different Regions of the Urinary Tract; Factors Influencing the Nephrogram and Pyelogram.- 1. Effects of Plasma Iodine Concentration.- 2. Effects of Urine Iodine Concentration.- II. Urinary Tract Volume Changes.- 1. Urine Flow.- 2. Theoretical Effects of Changes.- 3. Experimental Effects of Changes.- D. Pharmacodynamics.- I. Intravenous Lethal Dose.- II. Causes of Death.- 1. Lung Edema and Red Blood Cell Changes.- 2. Nephrotoxicity.- III. Other Adverse Reactions.- IV. Advantages of Ratio-3 Media.- E. Methods of Investigative Uroradiology.- I. Introduction.- 1. Choice of Species.- 2. Anesthesia.- 3. Surgical Procedures.- II. Assays for Contrast Media.- III. Methods for the Measurement of the Depth of the X-Ray Attenuating Layer.- 1. Planimetry.- 2. Urine Flow.- IV. Methods for Studying Excretion Mechanisms.- 1. Clearance of Contrast Media.- 2. Tubular Micropuncture and Microperfusion.- 3. Cell Culture.- V. Methods for Studying Renal Pharmacodynamics.- 1. Urine Osmolality.- 2. Ability to Concentrate Urine.- 3. Urine Flow.- 4. Vascular Changes.- 5. Glomerular Damage.- 6. Tubular Damage.- References.- 3 Contrast Media in the Cardiovascular System.- A. Introduction.- B. Classification of Cardiovascular Actions of Contrast Media.- C. Importance of Experimental Conditions.- I. Influence of the Experimental Model Used for Studying Cardiovascular Effects of Contrast Media.- II. Influence of the Site of Injection of Contrast Media.- D. Specific Effects.- I. Electrophysiologic Cardiac Effects.- 1. Impulse Generation.- 2. Impulse Conduction.- 3. Arrhythmias.- 4. Electrocardiographic Changes.- II. Hemodynamic Cardiac Effects.- 1. Hemodynamic Changes During Contrast Ventriculography.- 2. Use of Contrast Media as a Stress Test in Coronary Artery Disease.- III. Direct Myocardial Effects.- 1. Isolated Heart and Isolated Cardiac Tissue.- 2. Intracoronary Administration in the Intact Heart.- 3. Effects on Ischemic Myocardium and Failing Myocardium.- 4. Mechanism of Action of Direct Cardiac Effects.- 5. Clinical Evaluation of Contrast Media Used for Coronary Arteriography.- IV. Reflex or Neurally Mediated Circulatory Effects.- 1. Vascular Effects.- 2. General Circulation and Limb Circulation.- 3. Renal Circulation.- 4. Splanchnic Circulation.- 5. Carotid Circulation.- 6. Coronary Circulation.- 7. Microcirculation and Vascular Endothelium.- E. Summary.- References.- 4 Basic Methods of Investigative Cardiovascular Radiology.- A. Introduction.- B. Contrast Media.- I. Pharmacological Evaluation of Radiographic Contrast Media.- C. Experimental Cardioradiographic Visualization.- D. Choice of Experimental Animals.- I. Infrahuman Primates.- II. Cats.- III. Calves.- IV. Rabbits.- V. Pigs.- 1. Catheterization: Implantation of Chronic Catheters.- 2. Acute Catheterization.- VI. Dogs.- E. The Laboratory for Cardiovascular Contrast Media Research.- F. Cardiovascular Catheterization.- G. Animal Models of Cardiovascular Pathological States.- References.- 5 Contrast Media for Imaging of the Central Nervous System.- A. Introduction.- B. Angiographic Contrast Media in Neuroradiology.- I. Current Ionic Contrast Media.- 1. Cranial Angiography.- 2. Spinal Cord Angiography.- II. Newer Nonionic Monomers and Monovalent Dimer in Neurovascular Use.- C. Intrathecal Contrast Media.- I. Intrathecal Visualization.- II. New Developments in Intrathecal Contrast Media.- References.- 6 Basic Methods of Investigative Neuroradiology.- A. Introduction.- B. Anesthesia.- I. Premedication.- II. Injectable Anesthetics.- III. Volatile Anesthetics.- C. Neurovascular Experimental Methods.- D. Experimental Methods for the Subarachnoid Space.- 1. Choice of Animal.- 2. Methods of Access to the Subarachnoid Space.- E. Toxicity Screening of Experimental Compounds.- 1. Aversion Conditioning.- 2. Electrophysiological Methods.- References.- 7 Hepatic Disposition and Elimination of Biliary Contrast Media.- A. Introduction.- B. Anatomic Considerations.- I. Liver Anatomy.- II. Liver Blood Flow.- III. Classic Liver Lobule.- IV. Hepatic Cellular Anatomy.- V. Gallbladder Anatomy.- C. Biliary Physiology.- I. Composition of Bile.- II. Bile Formation.- 1. Canalicular Bile Flow.- 2. Ductular Bile Flow.- III. Hepatocyte Cytoskeleton and Bile Flow.- D. Pharmacokinetic Principles.- E. Cholecystographic and Cholangiographic Contrast Media.- I. Physicochemical Properties.- II. Intestinal Absorption.- III. Transport in Blood.- IV. First-Pass Effect.- V. Hepatic Uptake.- VI. Biotransformation.- VII. Biliary Excretion.- F. Concentration of Contrast Media.- I. Choleresis.- II. Biliary Concentration.- III. Electrolyte Composition.- G. Gallbladder Function.- H. Enterohepatic Circulation.- J. Renal Excretion.- K. Toxicity.- L. Future for Biliary Contrast Media.- References.- 8 Laboratory Techniques for Studying Biliary Contrast Media.- A. Introduction.- B. Choice of Animal Species.- C. Anesthesia.- D. Holding and Restraint.- E. Administration of Anesthetic.- F. Cannulation of Veins.- G. In Vivo Animal Preparation.- H. In Vitro Liver Preparations.- J. Instrumental Methods of Analysis.- I. Spectrophotometer.- II. Fluorescent Excitation Analysis.- III. Chromatographic Analysis.- K. Methods of Analysis.- I. Bilirubin.- II. Iodine (Chemical).- III. Bile Salts.- IV. Protein.- References.- 9 Contrast Media in Lymphography.- A. Introduction.- B. Methods of Lymphography.- C. Physiology and Pharmacology of Lymphokinetics.- D. Animal Models in Investigative Lymphangiology.- E. Experimental Contrast Media for Lymphography.- Re…