Blunderbuss to Mickey Mouse
The Evolution of Antiarrhythmic Targets
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In an era that finds us continually bombarded with numbers and images about threats, both real and imagined, a threat as old as the Bible that continues its dangerous course is that of cardiac arrhythmia.
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“… [My] heart trembleth and is moved out of its place,” said Elihu in the Book of Job1; if not a run of ventricular tachycardia, perhaps a paroxysm of atrial fibrillation.
“Palpitations rebelles” respond favorably to a suspension of cinchona and rhubarb, noted Senac in 1749,2 thereby demonstrating the effect of a quinidine-like molecule on what was presumably atrial fibrillation.
Quinidine terminates episodes of palpitations, said a patient to Wenckebach in 1914, and in 1918, Frey observed the superiority of quinidine to quinine as an antiarrhythmic agent. In testing quinidine, he used a drug developed by Pasteur in 1853 as an antimalarial alternative to quinine and cinchina.2
The year of Wenckebach’s observation,2 1914, was the same year in which George Ralph Mines3 published his initial experiments on reentry, observations on “circulating excitations in heart muscles and their possible relation to tachycardia and fibrillation” that were seminal to the field. That year was little more than a decade after Einthoven’s description of the ECG,4,5⇓ which rapidly became and has since remained the primary tool facilitating both our understanding and our diagnosis of arrhythmias during these 100 years since its invention.
The decades after the first therapeutic application of quinidine saw the testing and addition to arrhythmia therapy of drugs such as procaine, procainamide, ajmaline, and diphenylhydantoin.2 By the end of the 1960s, with propranolol and lidocaine available, there seemed to be great promise in the evolution of meaningful drug treatment. This was not only the product of work in drug development, but also of …