B. Raymond Fink Sheldon Roth and Keith Miller have asked me to record that the Third Conference on Molecular and Cellular Mechanisms of Anesthesia was held in Calgary last May "in my honor. " Such was my dear friends' gracious way of continuing a series that began at the University of Washington, where I hosted two, four, or five previous ones, 1,3-6 depending 2 on how far back one wishes to count. At that, Seattle took up where Paris left off in 1951. These occasions create their own unforgettable memories. This book captures the fine, invigorating ambience of the University of Calgary and the exciting explorations and com panionship of a gathering in a frontier territory of neuroscience. So, floreant symposia. They have progressively refined the quarry, from pathway to synapse to lipoprotein membrane to receptor and single channel, in heuristic convergences of neuronal physiology, biochemistry, and pharmacology. Nevertheless, the anesthesiologist in me senses a certain disquiet, a certain claustrophobia provoked by the narrow confines of micropipettes. How much more tubular must tunnel vision become before the desired broad view emerges? At present, the advances in molecular neurobiology seem continually to increase the apparent complexity of the total problem and the conceptual distance between the reductionists in the laboratories and the holists in the operating rooms. Happily, what is also growing is the excitement in trying to bridge the gap. Perhaps it would be timely to regard general anesthesia not as a state but as a syndrome.
In spite of ingenious experiments, imaginative theories, and unshakable faith in supreme forces, there is no way to know how life began. What is certain is that in the course of the development of the universe existing sources of energy fused to generate atoms, and atoms mingled to become small molecules. At some point by chance or design-according to one's belief, but no one's evidence-small molecules such as hydrogen, oxygen, carbon dioxide, water, and ammonia reacted to yield larger molecules with the property most essential to life: self-replication. Such molecules had to achieve a proper balance between the stability needed for their survival in the environment and the mutability for the generation of many forms of life. How amino acids were created or how DNA, RNA, and proteins developed remains a mystery. But we know that a simple core of nucleic acid embedded in a protein coat made the simplest unit of life (except for viroids). Whether viruses are a primitive or degenerated form of life is not known. Once proteins appeared, their great structural plasticity allowed them to react with other elements such as sulfur, iron, copper, and zinc. After an incalculable number of years, some of the proteins became capable of catalyzing the synthesis of new nucleic acids, new proteins, and other compounds such as polysaccharides and lipids.
Topics covered in this volume include: molecular and cellular mechanisms of general anaesthesia; developments in neuromuscular transmission; and management of the brain injured patient presenting for non-neurosurgical procedures.
Leading investigators critically evaluate the latest information on how anesthetics work at the molecular, cellular, organ, and whole animal level. These distinguished experts review anesthetic effects on memory, consciousness, and movement and spell out in detail both the anatomic structures and physiological processes that are their likely targets, as well as the cellular and molecular mechanisms by which they operate. Comprehensive and authoritative, Neural Mechanisms of Anesthesia draws together and critically reviews all the recent research on anesthetic mechanisms, highlighting the precise routes along which these substances operate, and how this deeper understanding will lead to the design of effective drugs free ofundesirable side effects.
This volume contains selected papers presented at the Sendai International Sympo sium on Molecular and Cellular Mechanisms of Cardiovascular Regulation held from May 10-12, 1995, to honor the contributions ofProfessorNorio Taira, Chairman of the Department of Pharmacology (1972-1995), Tohoku University School of Medicine, Sendai, Japan. The Department of Pharmacology at Sendai has a long tradition of significant contribution to the development of drug therapy for cardiovascular diseases. The late Professor Koroku Hashimoto, the predecessor of Professor Norio Taira, first suggested the mode of action of calcium antagonists and their potential usefulness in therapy of ischemic heart disease and hypertension at an early stage of their development. The need for greater understanding of the pathophysiology of cardiovascular dis eases is more critical now than ever before because modern advances in basic and clinical sciences have prolonged the average life expectancy. Using a wide range of molecular and electrophysiological techniques, major advances are occurring frequently in the field of cardiovascular physiology and pharmacology. Such multifaceted approaches are preferred because human cardiovascular diseases are complex, requiring multiple interventions and an in-depth understanding of molecular mechanisms underlying the disease. The first section of this book focuses on molecular mechanisms of ion channel regulation. Eight of ten chapters in this section are devoted to the recent advances in molecular characterization and regulation of various types of potassium channels in cardiac, vascular, and neuronal tissues. A discussion of the structure and function of sodium and calcium channels is also included.
Some important constraints of anesthesia must be taken into consideration when the pharmacological properties of modern anesthetics are discussed. The most imp- tant of these could be that the target effect be achieved preferably within seconds, at most within a few minutes. Similarly, offset of drug action should be achieved within minutes rather hours. The target effects, such as unconsciousness, are pot- tially life-threatening, as are the side effects of modern anesthetics, such as respi- tory and cardiovascular depression. Finally, the patient’s purposeful responses are not available to guide drug dosage, because, either the patient is unconscious, or more problematically, the patient is aware but unable to communicate pain because of neuromuscular blockade. These constraints were already recognised 35 years ago, when in 1972 Volume XXX entitled “Modern Inhalation Anesthetics” appeared in this Handbook Series. The present volume is meant as a follow up and extension of that volume. At the beginning of the 1970’s anesthesia was commonly delivered by inhalation, with only very few exceptions. The clinical understanding of that time considered anesthesia as a unique state achieved by any of the inhalation anesthetics, in- pendent of their specific molecular structure. “The very mechanism of anesthetic action at the biophase” was discussed within the theoretical framework of the “u- tary theory of narcosis”.