Chronopharmacology of Cardiovascular Diseases

Abstract

Heart rate was one of the earliest physiological functions reported not to be constant throughout 24 h (see P. Lavie, personal communication; Aschoff 1992). As early as the beginning of the seventeenth century daily variations, as well as a rapid increase in pulse rate on awakening, were described (Struthius 1602); later on, in the eighteenth and nineteenth centuries, general observations and even detailed data on daily heart rate variation and pulse quality were published (Zimmermann 1793; Reil 1796; Falconer 1797; Hufeland 1797; Autenrieth 1801; Wilhelm 1806; Barthez 1806; Knox 1815). Moreover, the pulse of a healthy subject measured in the late afternoon was frequently used by musicians as a readily available “metronome” (Quantz 1752). The introduction of the pulse-watch by Floyer (1707–1710) and, moreover, the introduction of a “third hand” into the clock to measure precisely the seconds allowed determination of changes in pulse rate (Zimmermann 1793). It is of interest to note that the symptoms of “office hypertension or white coat hypertension” — nowadays of increasing medical importance (see Pickering et al. 1994b; Krakoff 1994) — were precisely described more than 250 years ago by Hellwig (1738), when he reported on pronounced changes in the patient’s pulse on the appearance of the doctor (“Vor allen Dingen stehet aber zu wissen, daß der Pulse sich mercklich verändern ... könne, wozu nicht wenig Anlaß giebet die Ankunft des Medici”). He, therefore, recommended the doctor to sit down and to talk to the patient for a while before studying the quality of the pulse once or several (!) times, a recommendation reflecting our modern guidelines. Shortly afterwards, de Bordeu (1756) named the same observation “le pouls du médicin” (see Lemmer 1995).

This paper is dedicated to the pioneers in chronopharmacology, Alain Reinberg, and in chronobiology, Jürgen Aschoff.