1 Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. We therefore studied the reproducibility of power spectral analyses of blood pressure and heart rate fluctuations measured by a non-invasive finger plethysmographic method in 24 healthy volunteers. 2 Intra-observer reproducibility was assessed from measurements obtained on 3 consecutive days and 1 month later in each subject. Inter-observer reproducibility was assessed by comparing measurements made by two observers on one occasion. 3 There was no significant difference in standard haemodynamic and spectral analysis parameters (low frequency: 60-130 mHz and high frequency: respiration rate ± 30 mHz) measured on 3 consecutive days and 1 month later in each subject. The standard deviation of differences between systolic blood pressure or heart rate oscillations on different occasions was in the 150-200 and 50-100 mm Hg Hz-1/2 or beats min-' Hz-"/2 range for low frequency and high frequency oscillations respectively. Similar results were found when inter-observer reproducibility was considered. 4 From these results, we derived a sample-size table giving the number of subjects to be included in studies of cross-over or parallel design in order to detect a nonrandom difference in spectral analysis parameters. For example, detection of a 200 mm Hg Hz-1/2 difference in low frequency oscillations of systolic blood pressure at an alpha and a beta risk of 0.05 and 0.10 respectively would require the inclusion of approximately 15 subjects in a cross-over design study and 50 subjects in a parallel design study. 5 We conclude that, under our experimental conditions, non-invasive measurements of blood pressure and heart rate oscillations are reproducible. This technique can be used to assess the influences of diseases and drugs on the autonomic nervous system using a reasonably small number of subjects.

In order to compare the intensity and the duration of the pain following the subcutaneous injection of low molecular weight heparins, 0.4 ml nadroparin, 0.4 ml enoxaparin and 0.4 ml placebo (NaCl 0.9%) were administered at 1 week intervals to 12 healthy volunteers in a randomised, double-blind, three-period study. Pain was assessed by visual analogue and verbal category scales. Based on visual analogue scale scores, nadroparin resulted in significantly less pain than enoxaparin at 1 and 5 min after injection (6.2 ± 2.6 mm vs 21.9 5.9 mm; P < 0.05 and 3.5 + 1.5 mm vs 14.3 ± 4 mm; P < 0.05, respectively, mean s.e. mean). Similar results were obtained using verbal category scale. Confidence interval testing for difference between groups showed that nadroparin injection resulted in less pain than enoxaparin at 1 min (-15.8: -31.2 to -0.4 mm).

Background Nitrate tolerance is associated with a loss in the hemodynamic response to nitrate during repeated administration. Nicorandil is a new potassium channel agonist with additional nitrate properties. The aim of this study was to determine whether 7‐day nicorandil (10 mg orally twice a day) administration attenuates the response to single‐dose intravenous nitroglycerin (0.45 mg over 1 minute) in comparison with 7‐day intermittent nitroglycerin patch administration (10 mg for 16 of 24 hours). Methods This was an open, randomized crossover study performed in 12 healthy volunteers. Blood pressure, heart rate, and their oscillations were measured with use of a noninvasive device. Low‐frequency oscillations (66 to 129 mHz) of blood pressure reflect sympathetic activity. Reflex sympathetic activation was measured as after versus before intravenous nitroglycerin difference in low frequency oscillations of blood pressure and heart rate on day 0 and day 7 of each treatment period. Measurements after single‐dose intravenous nitroglycerin included the maximum decrease in systolic blood pressure and maximum increase in heart rate and sympathetic activation. Tolerance in each group was assessed as the difference in each parameter between day 7 and day 0. Results Attenuation of the intravenous nitroglycerin‐induced decrease in systolic blood pressure (day 7 − day 0) was −10 ± 10 mm Hg during use of the nitroglycerin patch and −2 ± 11 mm Hg during nicorandil (p = 0.03). Similarly, the change in low frequency oscillations of systolic blood pressure was − 79 ± 144 mm Hg · Hz−1/2 during nitroglycerin administration and 60 ± 139 mm Hg · Hz−1/2 during nicorandil administration (p = 0.04). Conclusion These results indicate that 7‐day administration of nicorandil does not attenuate single‐dose intravenous nitroglycerin‐induced hemodynamic changes or sympathetic activation. In healthy volunteers and at this dosage (10 mg twice a day), cross tolerance between nicorandil and nitroglycerin does not occur.