In healthy male top athletes several functions were measured after either a westbound flight over six time-zones (WEST: Frankfurt-Atlanta; n = 13) or an eastbound flight over eight time-zones (EAST: Munich-Osaka; n = 6). Under either condition the athletes performed two standardized exercise training units in the morning and in the afternoon within 24 h, investigations were done as controls in Germany and on day 1, 4, 6, and 11, after arrival. The primary aim of the study was to evaluate the effect of time-zone transitions on the 24h profiles of blood pressure (BP) and heart rate (HR) using an ambulatory BP device (SpaceLabs 90207), for up to 11 d after arrival at the destination. As additional parameters, we studied jet-lag symptoms, training performance, and training coordination by using visual analog scales. Finally, oral temperature and grip strength were measured, and saliva samples were analyzed for cortisol and melatonin. The study showed that all functions were disturbed on the first day after arrival at the destination, jet-lag symptoms remained until day 5-6 after WEST and day 7 after EAST, training performance was worst within the first 4 d after WEST. In accordance with earlier reports, cortisol, melatonin, body temperature, and grip strength were affected in their 24h profiles and additionally modified by the training units. Surprisingly, BP and HR were not only affected on the first day but also the time-zone transition led to an increase in BP after WEST and a decrease in BP after EAST. However, the training units seemed to influence the BP profile more than the time-zone transitions. HR rhythm was affected by both time-zone transitions and exercise. It is concluded that not only jet-lag symptoms but also alterations in physiological functions should be considered to occur in highly competitive athletes due to time-zone transition and, therefore, an appropriate time of reentrainment is recommended.

Intravenous injections of indocyanine green (ICG) were given to 10 healthy supine subjects at 02.00, 08.00, 14.00 and 20.00 h. ICG plasma half‐life, plasma clearance and estimated hepatic blood flow (EHBF), but not volume of distribution, varied significantly with time of day with EHBF being greatest at 08.00 h. This circadian rhythm in EHBF should be considered when evaluating the kinetics of high‐clearance drugs at different times of day.

Circadian phase dependency in pharmacokinetics and hemodynamic effects on blood pressure and heart rate of different galenic formulations of nifedipine (immediate-release, sustained-release, and i.v. solution) were studied in healthy subjects or in hypertensive patients. Pharmacokinetics of immediate-release but not sustained-release and i.v. nifedipine were dependent on time of day: immediate-release nifedipine had higher Cmax (peak concentration) and shorter tmax (time-to-peak concentration) after morning than evening application, and bioavailability in the evening was reduced by about 40%. Circadian rhythm in estimated hepatic blood flow as determined by indocyanine green kinetics may contribute to these chronokinetics. A circadian time dependency was also found in nifedipine-induced effects on blood pressure and heart rate as monitored by 24-h ambulatory blood pressure measurements. In conclusion, the dose response relationship of oral nifedipine is influenced by the circadian organization of the cardiovascular system as well as by the galenic drug formulation.

A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.

To evaluate whether circadian rhythms in blood pressure and heart rate are influenced by age, we analyzed 24-h ambulatory blood pressure and heart rate recordings from 31 patients with primary hypertension. Data were collected during hospitalization, after a drug-free run-in period. Set times were administered for lights-on, meals, and lights-off. Daytime napping was prohibited. The patients were divided into sex-matched groups of young (group I: 25-45 years, n = 9), middle-aged (group II: 47-57 years, n = 11), and old (group III: 57-74 years, n = 11) subjects. Hourly data were analysed by fitting a two-component cosine function (24- and 12-h periods). Amplitudes of the circadian rhythms in systolic blood pressure and heart rate were significantly reduced with age. This finding could be partly attributed to the recording of higher nocturnal values in older patients. Elderly hypertensives also evidenced a significantly greater ultradian component (12-h period) in the systolic blood pressure rhythm than did young patients, with the secondary afternoon decline in blood pressure being more pronounced in groups II and III. The 24-h acrophase of heart rate was found to occur approximately 1.6 h earlier than that of systolic blood pressure in the young group (p < 0.01). This phase advance of heart rate compared with systolic blood pressure was reduced to 1 h in group II (p < 0.05) and was not evident in group III (p > 0.1). These results indicate that circadian blood pressure and heart rate profiles of primary hypertensives change with age. Since measures were obtained in a typical clinical setting, these findings have implications for the diagnosis and treatment of hypertension in the elderly. The marked afternoon decline in blood pressure for the elderly patients may also render conventional cosinor analysis inappropriate for accurate description of the circadian rhythms of geriatric hypertensives.