Modifications of the isolated frog heart preparation in Carl Ludwig's Leipzig Physiological Institute: relevance for cardiovascular research.

摘要

Carl Ludwig was the first physiologist to systematically study isolated organs (heart, muscle, kidney, liver, lung). In his Leipzig Physiological Institute, the isolated perfused frog heart preparation was established in 1866 by Elias Cyon. This preparation was subsequently subjected to various modifications, and many important observations were made by scientists such as Joseph Coats, Henry Pickering Bowditch, Luigi Luciani, Michael Joseph Rossbach, Hugo Kronecker and Otto Frank. The influence of filling pressure on contraction amplitude, the all-or-none law of the heart, the absolute refractory period, postextrasystolic potentiation, the staircase ('Treppe') phenomenon and the dependence of heart function on oxidative metabolism were discovered. The negative chronotropic and inotropic effects of vagus nerve stimulation were also first documented, and a model to induce arrhythmias was established. The isolated frog heart preparation became a widely used standard model for teaching and for basic cardiovascular research. Sidney Ringer discovered the essential role of calcium ions for heart function. Otto Loewi discovered the chemical transduction mechanism of the vagus with acetylcholine as transmitter. In more recent times, the cyclical changes in cAMP and cGMP that occur during the cardiac cycle were first described in the frog heart by Wollenberger and associates. Thus, the isolated perfused frog heart established and modified in Carl Ludwig's Leipzig Physiological Institute led not only to the discovery of basic phenomena, but also to observations that became the basis for concepts to be developed and elaborated later. Furthermore, the isolated perfused frog heart was the starting point for the development of the isolated mammalian heart in the retrogradely perfused, nonworking mode in the heart-lung modification and in the working heart preparation.