Atrial fibrillation: a historical perspective.

Atrial fibrillation (AF) has undoubtedly become one of the most well-studied arrhythmias today in terms of pathophysiology and diagnostic and therapeutic (interventional) electrophysiology. Although it lends itself to an apparently easy diagnosis on the surface electrocardiography, myriad electromechanical mechanisms underlie its origin. We have now reached an era of technology that makes AF not only "treatable" but potentially "curable." This article aims at walking through the historical "corridors" and "mazes" that led to the present day understanding of this common yet complex arrhythmia.

Atrial fibrillation: a historical perspective.

Atrial fibrillation (AF) undoubtedly has become one of the most well studied arrhythmias today in terms of pathophysiology and diagnostic and therapeutic (interventional) electrophysiology. Although it lends itself to an apparently easy diagnosis on a surface ECG, myriad electromechanical mechanisms underlie its origin. An era of technology has been reached that makes AF not only "treatable" but also potentially "curable." This article aims at walking through the historical corridors and maze that have led to the present-day understanding of this most common yet complex arrhythmia.

Calcium channel antagonists: clinical uses--past, present and future.

The calcium channel antagonists are a mature group of drugs directed at cardiovascular diseases including hypertension, angina, peripheral vascular disorders and some arrhythmic conditions. Their sites and mechanisms of actions have been well explored over the past two decades and their interactions at the alpha(1) subunit of L-type channels (Ca(V)1.1-1.4) have made them valuable molecular tools for channel classification and localization. With the realization that other members of the voltage-gated calcium channel family exist--Ca(V)2.1-2.3 and Ca(V)3.1-3.3--considerable effort has been directed to drug discovery at these channel types where therapeutic prospects exist for a variety of disorders including pain, epilepsy, affective disorders, neurodegenerative disorders, etc. In contrast to the situation with the L-type channel antagonists success in developing small molecule antagonists of therapeutic utility for these other channel types has thus far been lacking. The reasons for this are explored and potential new directions are indicated including male fertility, bone growth, immune disorders, cancer and schistosomiasis.

[The concise history of atrial fibrillation]. / A pitvarremegés attekinto története.

The author reviews the history of atrial fibrillation, the most common sustained cardiac arrhythmia. The chaotic irregularity of arterial pulse was clearly acknowledged by most of physicians of the ancient China, Egypt and Greece. William Harvey (1578-1657), who first described the circulatory system appropriately, was probably the first to describe fibrillation of the auricles in animals in 1628. The French "clinical pathologist", Jean Baptist de Sénac (1693-1770) was the first who assumed a correlation between "rebellious palpitation" and stenosis of the mitral valve. Robert Adams (1791-1875) also reported in 1827 the association of irregular pulses and mitral stenosis. The discovery of digitalis leaf in 1785 by William Withering (1741-1799) brought relief to patients with atrial fibrillation and congestive heart failure by reducing the ventricular rate. From an analysis of simultaneously recorded arterial and venous pressure curves, the Scottish Sir James Mackenzie (1853-11925) demonstrated that a presystolic wave cannot be seen during "pulsus irregularis perpetuus", a term very first used by Heinrich Ewald Hering (1866-1948). Arthur Cushny (1866-1926) noted the similarity between pulse curves in clinical "delirium cordis" and those in dogs with atrial fibrillation. The first human ECG depicting atrial fibrillation was published by Willem Einthoven (1860-1927) in 1906. The proof of a direct connection between absolute arrhythmia and atrial fibrillation was established by two Viennese physicians, Carl Julius Rothberger and Heinrich Winterberg in 1909. Sir Thomas Lewis (1881-1945), the father of modem electrocardiography, studied electrophysiological characteristics of atrial fibrillation and has shown that its basic perpetuating mechanism is circus movement of electrical impulse (re-entry). After him, the major discoveries relating to the pathophysiology and clinical features of atrial fibrillation in the 20th century stemmed from Karel Frederick Wenckebach (1864-1940), Gordon Moe (1915-1989), Bernhard Lown (*1921) and Maurits Allessie. Over the past ten years, awareness has increased of transcatheter radiofrequency and cryoablation of non-valvular atrial fibrillation and the battle against formation of intraatrial thrombi for preventing cerebral thromboembolism.

Antiarrhythmic drug research.

This article was written as part of the 75th anniversary celebration of the British Pharmacological Society (BPS). It discusses antiarrhythmic drug research conducted by members of BPS, and as published in the British Journal of Pharmacology (BJP). BPS members, past and present, as well as antiarrhythmic manuscripts published in the BJP have been identified. From these data, the article attempts to semiquantitatively summarize results published in the journal, but only quotes selected manuscripts and individuals. Apologies are offered for omissions and errors, but as in any history, a writer's biases and opinions are unavoidable.