History of Medicine

         FURTHER TALES OF ANGINA: 

A REMEDY AT LAST

 

         Last month’s essay outlined the first descriptions of angina pectoris and its relation to coronary artery disease. William Jenner was probably the first to notice the association of the syndrome with calcification of the coronary arteries. He withheld publication of his findings to avoid frightening his friend and former teacher, John

Caleb Parry (Wikipedia)

Hunter. In 1799, Jenner’s colleague, Caleb Parry, a physician in Bath, published a monograph on angina in which he reveals the story of Jenner’s discovery, details three more cases that show diseased coronary arteries at autopsy, and unfortunately confuses the picture by adding syncope as an accompanying symptom in some cases. 

         Osler, in his 1892 textbook, called angina a rare disease, reiterating its rarity in a series of lectures published in 1897. Regarding the cause of anginal chest pain, Osler noted that hardened coronary arteries are

William Osler (Wikipedia)

found in many cases with no angina, making it uncertain what actually caused the pain. He listed three main possibilities: a neuralgia of the cardiac nerves, a cramp in the heart muscle, or an extreme tension in ventricular walls (or in the associated nerves) caused by dilatation of the heart from insufficiency of coronary blood flow.

         Treatment since Heberden’s time and until the late 19^th century consisted in administration of spirits, plasters, bleeding (to relieve “plethora”), and sometimes opiates or chloroform. Removing a few ounces of blood often prevented recurrent attacks for a short period, probably related to a lower blood pressure. Details of the physiology involved, however, were far from clear. 

         Nitroglycerin, the “modern” treatment for angina pectoris, originated, strangely enough, in homeopathic practice. 

         Dr. Samuel Hahnemann, a well-trained German physician, began the homeopathy movement in 1796. It was based on his idea

Sanuel Hahnemann (Wikipedia)

that if the effects of a drug caused symptoms resembling those of a particular disease, then small doses of that medication would counteract the action of the same disease – “like cures like.” The idea proved attractive and, possibly because patients avoided the traditional bleeding and purging, the practice of homeopathy grew. 

         The chief founder and organizer of homeopathy in America was Constantin Hering. Born and educated in medicine in Germany, Hering was asked by a professor, while training in Leipzig, to write an essay against homeopathy. But when he studied the works of Hahnemann, he became a convert. He landed in America after a shipwreck near the New England coast. He decided to stay, opened a homeopathy practice in Philadelphia, and was instrumental in founding the first school of homeopathy in America. He devoted much time to “proving” medications. Proving was a method, initiated by Hahnemann, by which medications were tested systematically on

Constantin Hering (National Library of Medicine)

humans to observe and record their effects. It was perhaps the first such evaluation of items in the pharmacopeia, an advance over methods of regular physicians.

         Hering was aware of nitroglycerin. An Italian chemist, Ascanio Sobrero (whose face was scarred from an explosion and who knew Alfred Nobel), first synthesized nitroglycerin in 1847 while seeking a better explosive than the available “gun cotton.” Hering “proved” nitroglycerin as early as 1849 and noted that small doses on the tongue rapidly produced throbbing headaches and a rapid pulse, effects Sobrero had also noted. He gave the name “glenoin” to nitroglycerin and, in diluted doses, it became a treatment for headaches and sometimes palpitations. Occasionally it produced an oppressive feeling or even pain in the chest, but it was never promoted for angina, which homeopaths agreed was a rare condition.

         In England, homeopaths were also using glenoin. A British regular physician, Alfred Field, obtained the substance from a homeopathic chemist and reported, in 1858, a single case of a woman with angina-like chest pains who was relieved by nitroglycerin. Others with varied non-chest pains also had relief. The first to use it specifically for angina pectoris was William Murrell, a physician at the Royal Hospital for Diseases of the Chest. He had worked under Burton-Sanderson, one of England’s finest physiologists, and Sydney Ringer (of Ringer’s solution) and was thus trained in experimental techniques. Having read the papers of Sobrero and Field, Murrell made a 1% solution of nitroglycerin and placed a small amount on his tongue. He noted a headache and a sudden bounding of his pulse, so forceful that, just as a patient had entered his office, “I hardly felt steady enough to perform percussion” and, “The pen I was holding was violently jerked with every beat of the heart.” He took nitroglycerine many more times and began to administer it to others, recording pulse, symptoms, and the like. 

         Murrell was aware that the effects of nitroglycerine resembled those of amyl nitrate, an inhaled substance first described as a treatment for angina in 1867. In 1879, he published his experiments

Murrell's first article on nitroglycerine.

with nitroglycerin in a series of four articles, showing that its effects were similar to amyl nitrate but with faster onset of action and longer duration. As an attempt to prevent angina, he gave it as a small tablet to take four times a day. The frequency of anginal attacks in three patients tested diminished, as did the intensity. However, one patient found it easier to simply take a nitroglycerine tablet on the tongue when an attack came on, after which he obtained quick relief. This use of a former homeopathic remedy became the standard approach to managing angina up to the present time. Few medical remedies have enjoyed such a long life.

 

SOURCES:

Fye, B, “Nitroglcerin: a homeopathic remedy.” 1986; Circulation 73: 21-9.

 

Murrell, W, “Nitroglycerine as a remedy for angina pectoris.” 1879; Lancet v 1, 80-81, 113-15, 151-2, 225-7.

 

Osler, W, Lectures on Angina Pectoris and Allied States. 1897; Appleton & Co., New York.

 

Eastman, A M, Life and Reminiscences of Dr. Constantine Hering. 1917; reprint from The Hahnemannian Monthly, 1917, privately printed.

 

Field, A G, “Toxical and medicinal properties of nitrate of oxide of glycyl.” 1858; Med Times Gazette 16: 291.