doi: 10.1161/01.RES.0000186187.89219.b3
© 2005 American Heart Association, Inc.
In Memoriam |
Silvio Weidmann 1921–2005
Silvio Weidmann’s death on July 11, 2005, brings to a close a heroic period for cellular cardiac electrophysiology. Silvio was the first to record accurate cardiac transmembrane action potentials and to identify the roles of sodium and potassium currents in excitation, conduction, and repolarization in cardiac cells. From his experiments in the 1950’s has grown the entire field of cardiac electrophysiology. His ideas and their influence on those who entered the field after him set the standard for progress in the last half-century. The field is now a cornerstone of clinical cardiac care.
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Silvio graduated from the University of Bern Medical School in 1946, after interruptions for service in the Swiss Army. In 1948 he went from Uppsala to Cambridge, England, to work with future Nobel laureate Alan Hodgkin—an experience that set the stage for Silvio’s major contributions. After four years back in Bern, he spent a year at SUNY, Downstate Medical School in 1954, where young Brian Hoffmann was beginning his work. Although initially tempted to stay in New York, he returned to Bern, which became a magnet for many of the young people entering the field. During my first stay there from 1963 to 1964 my colleagues were Mario Vassalle, Harald Reuter, and Hans-Christoph Lüttgau, preceded by Hans Hecht and Edward Carmeliet and followed by Boris Surawicz, Gerhard Giebisch, Earl Wood, Peter Hess, and Robert Weingart (to mention a few). Many who did not work in Bern came to seek Silvio’s advice. Subsequently, he became chairman of the Hallerianum, the Department of Physiology, and Chancellor of the University of Bern. Throughout, he continued his experimental laboratory and support for such Physiology faculty in Bern as André Kléber.
A decisive event in Silvio’s career was his arrival in Cambridge during the summer of 1948, shortly after Alan Hodgkin returned from a visit to the University of Chicago. There, Hodgkin saw Cole’s first pictures of voltage-clamped squid giant axon, and Gilbert Ling taught him to make the new fine-tipped microelectrodes. That summer, Hodgkin and his student Andrew Huxley began their revolutionary work on the ionic basis of the nerve action potential. We know the exact moment in Silvio’s career when he began to study heart muscle. On July 16, 1949 in Cambridge during afternoon tea, Wilhelm Feldberg offered Silvio the heart of a dog that had been used for student demonstration of Starling’s Law. Staying that night and using the new microelectrode technique, he recorded the first quantitatively-accurate cardiac action potential. In October 1949, he and Edouard Coraboeuf reported this work,1 shortly before measurements of the frog cardiac action potential were reported by Walter Woodbury, his brother Lowell, and Hans Hecht.2 Consistent with his professional philosophy, Silvio never claimed to be first.
Armed with intimate understanding of the Hodgkin-Huxley work on nerve, Silvio returned to Bern and developed a voltage clamp for cardiac Purkinje cells. Working alone, he demonstrated that excitation and conduction resulted from a transient voltage-dependent sodium current that was blocked by local anesthetics.3,4 He showed that during the long plateau of the action potential the membrane resistance greatly increased, a process now known as HERG-based inward rectification.5 Recognizing that electricity must flow between cells, he measured the flux of radioactive potassium across the intercalated disk.6 In a rare collaboration, he and Earl Wood showed the influence of membrane voltage and of extracellular calcium on contraction.7 As always, he would only publish experimental observations he personally had made (he did once borrow some micropipettes from me).
Although Silvio’s seminal electrophysiological studies were the foundation of modern cardiac electrophysiology, his greatest impact was as a mentor of absolute integrity and an inspirational leader. He not only demanded the highest standard of quantitative science for himself, but he could correct others’ careless work without causing resentment—even inspiring them to do better. (His manuscript reviews were as good as signed in those days before the internet, because he used an old typewriter with damaged keys). His sage advice was always openly given, explaining why so many sought it. He disliked blatant competition, both because of the baser instincts and animosity it aroused and because there were so many questions that needed study. He was careful to protect time with his own family, and encouraged his colleagues to do the same. In summary, the field was better for the way Silvio lived, as well as for his experiments. At least a shadow of his legacy lives in those he mentored within his laboratory and throughout the field of cardiac electrophysiology.
References
1. Coraboeuf E, Weidmann S. Potential de repos et potentiels d’action du muscle cardiaque, mesurés á l’aide d’électrodes intracellulaires. CR Soc Biol Paris. 1949; 143: 1329–1331.
2. Woodbury LA, Woodbury JW, Hecht HH. Membrane resting and action potentials from single cardiac muscle fibers. Circulation. 1950; 1: 264–266.[Abstract]
3. Weidmann S. The effect of the cardiac membrane potential on the rapid availability of the sodium-carrying system. J Physiol. 1955; 127: 213–224.
4. Weidmann S. Effects of calcium ions and local anesthetics on electrical properties of Purkinje fibres. J Physiol. 1955; 129: 568–582.
5. Weidmann S. Effect of current flow on the membrane potential of cardiac muscle. J Physiol. 1951; 115: 227–236.
6. Weidmann S. The diffusion of radiopotassium across intercalated disks of mammalian cardiac muscle. J Physiol. 1966; 187: 323–342.
7. Wood EH, Heppner RL, and Weidmann S. Inotropic effects of eelectric currents. I. Positive and negative effects of constant electric currents or current pulses applied during cardiac action potentials. Circ Res. 1969; 24: 409–445.
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