Historical development of current concepts on central chemosensitivity.

The history of concepts on the mechanism of central chemosensitivity is reviewed with special emphasis on ideas that have remained valid or stimulating until today. Early physiologists considered chemoreception to be a property of respiratory neurones in the brainstem (Pflüger 1868; Gesell 1926, 1949; Winterstein 1910, 1921, 1956). It has not been elucidated by which mechanism acid/base disturbances cause cardiorespiratory adaption. The reaction theory focused on protons as being the decisive stimulus (Lehmann 1888, Winterstein 1921, Loeschcke 1982), but this issue can be adequately discussed only when the compartment where changes occur is taken into account (Jacobs 1920, Gesell 1940). Heymans and collaborators demonstrated in 1930 that chemoreception is not only possible by a central mechanism but also at the level of the peripheral chemoreceptors. Without solid evidence for such an assumption, the existence of specific 'receptors' for pH and/or pCO2 was postulated by von Euler and Söderberg in 1952. Several chemosensitive areas at the ventrolateral surface of the medulla oblongata were defined by Loeschcke and collaborators in a series of papers after 1958. Within these areas, however, a specific chemoreceptor has not been distinguished. On the other hand, a direct chemosensitivity of bulbospinal sympathoexcitatory neurones as an intrinsic property of these neurones has recently been demonstrated (Seller 1989). Therefore, coming back to the original concept of chemoreception as a function of central cardio-respiratory neurones appears to be the most promising path for future research.