Otto loewi and the chemical transmission of vagus stimulation in the heart

Main, Germany. After attending school in his native town he started to study medicine at the University of Munich in 1891 and completed his studies at the University of Strasbourg in 1896. He then took a course in inorganic chemistry in Frankfurt and spent a few months in the biochemical institute of Franz Hofmeister in Strasbourg. During 1897 and 1898,he worked at the City Hospital in Frankfurt. He became frustrated by the lack of therapy in the treatment of tuberculosis and pneumonia and decided to do research in basic medical science, in particular, in pharmacology. Otto Loewi succeeded in becoming assistant to Hans Horst Meyer at the University of Marburg and was appointed lecturer in 1900. In 1902, he spent some months in the laboratory of Henry Starling where he met W. M. Bayliss and Henry H. Dale. In 1909, he was appointed professor of pharmacology and chairman at the University of Graz, Austria. In 1936, together with Sir Henry Hallett Dale (1875–1968), he was awarded the Nobel Prize in Physiology or Medicine for their discoveries relating to chemical transmission of nerve impulses. When Austria was annexed by the Nazis in 1938, Loewi was forced to leave the country. He had been compelled to instruct the Swedish bank in Stockholm to transfer his Nobel Prize money to a Nazi-controlled bank. He fled first to Brussels, Belgium, where he spent some time as Visiting Professor at the Université Libre, and then to Oxford, Great Britain, where he was at the Nuffield Institute. In 1940, he moved to the U.S. and worked at the College of Medicine, New York, as Research Professor of Pharmacology. In 1946,he became an American citizen. He died in 1961. The work that led to the Nobel Prize was primarily concerned with the effects of vagus stimulation on heart function. In 1845, Eduard Weber (1806–1871) and his elder brother Ernst Heinrich Weber (1795–1878) had shown an interest in this issue. They demonstrated that electrical stimulation of parts of the brain in which the vagus originates, as well as stimulation of the vagus nerve itself, reproducibly slowed and eventually stopped the heart beat.At that time, however, the kymograph that Carl Ludwig introduced into physiologic research was not available, so that registration and documentation of the effect were not possible. The effects were therefore demonstrated by E. H. Weber during the meeting of the Italian natural scientists in Naples in 1845. The negative chronotropic and inotropic effects of vagus stimulation were also observed by Albert von Bezold and documented in the frog heart in Carl Ludwig’s (1816–1895) Leipzig Physiological Institute by Joseph Coats,a Scotsman from Glasgow. A frog was cut below the liver, and the sternum and front feet were excised, but a large skin patch was maintained to serve as a cover for the nerves and heart. The aorta was cannulated and connected with a mercury manometer. Another cannula was inserted into the atrium and connected to the reservoir,which contained reddish rabbit serum. The vagus nerve was stimulated with platin electrodes. This preparation was a nonrecirculating system in which the heart pumped the serum into the manometer and caused regular and consistent excursions of the mercury,which reflected the force developed by the heart. As soon as vagus nerve stimulation became effective,there was an immediate decrease in systolic and diastolic pressure,and beating stopped entirely. When the heart resumed its action, the rate was slower and the amplitude of contractions was lower. Both increased until the normal contraction pattern was attained. In this frog heartpreparation,Schmiedeberg tested the effect of atropine, muscarine, and nicotine. He demonstrated that the negative This section edited by J. Willis Hurst, M.D., and W. Bruce Fye, M.D., M.A.