Antiarrhythmic drugs.

The heart, and more specifically the heartbeat, has throughout history served as an indicator of well-being and disease, both to the physician and to the patient. Through one’s own heartbeat, one can feel the physiologic manifestations of joy, thrills, fear, and passion; the rigors of a sprint or longdistance run; the instantaneous effects of medications, recreational drugs, or toxins; the adrenaline of a rollercoaster ride or a penalty shootout in a World Cup final. Although the complexities of the heart continue to humble the scientists and physicians who study it, the heart is unique in that, despite the complexity of its physiology and the richness of both visceral and romantic imagery associated with it, its function can be distilled down to that of a simple pump, the function and dysfunction of which we now understand a great deal (see Chapter 21). The history of development of pharmacologic agents to correct abnormalities in heart rhythm is, however, emblematic of drug development as a whole: major successes combined with paradoxes, damaging side effects, and the often frustrating intransigence of what would seem the most intuitive targets for antiarrhythmics— ion channels. In ancient Greek, Egyptian, and Chinese cultures, the pulse was recognized as a means to assess health, and for millennia it was the only measure of cardiac physiology and pathophysiology. In second-century Rome, Galen’s work De Pulsibus became the first great treatise on the pulse as a window into human health and established Galen as the father of his discipline. It was not for another 1500 years that the great physician, scientist, and naturalist William Harvey, of Folkstone in England, published his landmark (and then controversial) work An Anatomical Exercise Concerning the Motion of the Heart and Blood in Animals. This introduced the theory that blood circulates throughout the body, a hypothesis tested rigorously by Harvey with experiments on animals and the cadavers of executed criminals. In the late 19th and early 20th centuries, Waller and Einthoven founded the field of electrocardiography, facilitating quantitative differential diagnoses of cardiac arrhythmias. This paved the way for modern cardiology and advances such ANTIARRHYTHMIC DRUGS