Accidental Medical Discoveries by Robert W. Winters

Author:Robert W. Winters
Language: eng
Format: epub
Publisher: Skyhorse Publishing
Published: 2016-04-08T04:00:00+00:00

Part V

Drugs that Affect the Heart

CHAPTER

14

Nitroglycerin and Amyl Nitrite: Boom!

There is a disorder of the breast marked with strong and peculiar symptoms considerable for the kind of danger belonging to it.…

—William Heberden, 1772

Introduction

Angina pectoris is a spasm of vise-like pain that occurs whenever the oxygen demand of the heart exceeds its oxygen supply due to an acute insufficient delivery of oxygen-laden blood by the coronary arteries. The underlying cause is arteriosclerosis of the coronary vessels. Angina pain appears suddenly; it is felt over the left chest above the heart, shoots up the neck, and goes down the left arm, often accompanied by shortness of breath and an impending sense of doom. The sufferer is obliged to stop whatever activity in which he is engaged and rest until the pain subsides.

In 1809, David Dundas described a patient seized with angina pectoris as follows: “He was seized with a considerable pain at the heart, and a difficulty of respiration, great palpitation, and great anxiety. He conceived that the smallest motion of the body has instantly destroyed him, and this dread seemed to have totally bereft him of the power of utterance.”

Two drugs, nitroglycerin and amyl nitrite, play prominent roles in the development of effective treatment for this disease. In 1844, Antoine Jerome Balard, the discoverer of bromine, was investigating the cause of spoilage of eau de vie de marc, a brandy made from distilled pressed grape pulp that is left over after wine has been made. He identified a volatile oily substance that proved to be amyl nitrite. The vapors provoked a severe headache, but he did not pursue studies of its physiological effects.

English chemist Frederick Guthrie, in studying the compound, wrote: “One of the most prominent of its properties is the singular effect of its vapor, when inhaled, upon the action of the heart. [If a few drops are inhaled after a lapse of fifty seconds, a sudden throbbing of the arteries is felt, immediately followed by flushing and an acceleration of the action of the heart.] These symptoms last for about a minute and then cease.” Guthrie attributed these symptoms to a dangerous contaminant, hydrocyanic acid. For this reason, amyl nitrite was regarded as a poison, and no further meaningful studies of its effects were forthcoming until 1865, when Benjamin Richardson (later Sir Benjamin) found that amyl nitrite produced dilatation of the capillaries in the web of a frog’s foot, which he saw under a microscope. As an unforeseen sidelight, Richardson also found that the substance had the ability to preserve flowers and dead animal tissue.

Thomas Brunton

A young physician, Thomas Brunton (later Sir Thomas) in Edinburgh, noted that patients with angina pectoris had elevated blood pressure, and he recalled witnessing some experiments of Dr. Arthur Gamgee in which amyl nitrite reduced the blood pressure in animals and humans. Brunton reasoned that both the fall in blood pressure as well as the flushing produced by amyl nitrite were due to dilation of blood vessels. If so, maybe the coronary vessels supplying

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