Cardiac Toxicology I [antikvár]

FOREWORD Academic toxicology has existed as a discipline for several decades. Scientific journals in the field of toxicology have appeared in the past 30 years. Anecdotal toxicology does go back to the age of Mithridates and beyond that to antiquity. However, we have progressed from the debates on the poisonous effects of newly introduced tomatoes in the 17th century to pharmacology, itself a daughter of physiology, and then to toxicology of drugs and other chemicals. Epidemics of chemical toxicity have affected most seriously the nervous system and its sensory appendages; also the skin, blood-forming organs, liver, kidney, and the musculoskeletal system, in the affected person and even in the offspring. Knowledge of direct cardiac toxicity is of fairly recent vintage. One of the first fruits of the discovery of electrocardiography was the demonstration of fatal ventricular fibrillation from the anesthetic chloroform. Toxicology has annexed enzymology, immunology and other aspects of molecular biology and pharmacology to increase our understanding. Thus, allylamine, a chemical used for the past 30 years to simulate coronary sclerosis, is now thought to produce myocardial necrosis through its metabolite (also a metabolite of cyclophosphamide), acrolein.* and possible depletion of reduced glutathione, such as occurs in other organs under other toxic circumstances. With the advent of hundreds of thousands of new chemicals, some deliberately and others adventitiously administered to man, it had become necessary to institute a National Toxicology Program (1966) and test chemicals on a priority basis for both acute and chronic toxicity. Considering that serious, even rapidly fatal cardiac effects have resulted from new and powerful drugs, e.g., antineoplastics, tricyclic antidepressants, adrenergic-vaso-constrictor and anti-adrenergic-vasodilator agents, this monograph is timely indeed. One need not go back to chloroform, cyclopropane, or even digitalis; Buechner did demonstrate its double-edged subendocardial necrosis back in the early thirties. Dr. Balazs who is an active worker in experimental drug effects on the heart, has assembled a galaxy of contributors, authorities in their own fields. Basic mechanisms, subtended in Volume I only indicate our large areas of ignorance, which the contributors are striving to dispel. The unearthing of such basic mechanisms should lead most productively to the prevention and control of drug and chemical cardiotoxicity. This is a worthy effort in special toxicology of vital organs, which should be useful to basic scientists, experimental toxicologists, drug and poison control authorities, clinical pharmacologists, industrial physicians and cardiologists alike. Arthur Ruskin, M.D. Rockville, Maryland March. 1981 * Boor, P. J. and Nelson, T. J., Toxicology, I, 53, March. 1981.