Ophthalmic timolol resembled intravenous timolol in terms of systemic bioavailability, plasma kinetics, and cardiopulmonary effects. Clinicians should pay attention to the high systemic bioavailability of ophthalmic timolol, because intensive systemic beta-blockade can be highly hazardous to aged patients suffering from cardiopulmonary diseases.

of biosignal analysis in assessing terbutaline-induced heart rate and blood pressure changes. Am J Physiol Heart Circ Physiol 282: H773-H781, 2002; 10.1152/ajpheart. 00559.2001.-The aim of this study was to characterize how different nonlinear methods characterize heart rate and blood pressure dynamics in healthy subjects at rest. The randomized, placebo-controlled crossover study with intravenous terbutaline was designed to induce four different stationary states of cardiovascular regulation system. The R-R interval, systolic arterial blood pressure, and heart rate time series were analyzed with a set of methods including approximate entropy, sample entropy, Lempel-Ziv entropy, symbol dynamic entropy, cross-entropy, correlation dimension, fractal dimensions, and stationarity test. Results indicate that R-R interval and systolic arterial pressure subsystems are mutually connected but have different dynamic properties. In the drug-free state the subsystems share many common features. When the strength of the baroreflex feedback loop is modified with terbutaline, R-R interval and systolic blood pressure lose mutual synchrony and drift toward their inherent state of operation. In this state the R-R interval system is rather complex and irregular, but the blood pressure system is much simpler than in the drug-free state. nonlinear dynamics; complexity; dimensionality; entropy TRADITIONAL LINEAR ANALYSIS methods of heart rate and blood pressure time series data, such as the time-and frequency-domain methods, measure the strength of oscillations in heart rate and blood pressure within a specific frequency range, for example, in the low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.4 Hz) bands. The spectral powers obtained can be used, for example, to estimate sympathetic and parasympathetic nervous activity and, with cross-spectral approaches, to characterize arterial baroreflex functions. Generally, the linear methods (time-and frequencydomain methods) are useful and have been widely adopted in studies of health and disease because results from linear methods are quite easy to interpret in physiological terms. But they also have limitations, and criticisms have been raised against their use (5).Multiple feedback loops in cardiovascular regulation systems make rapid adaptations possible under a large variety of physiological and environmental conditions. In analyzing heart rate and blood pressure time series with traditional linear methods, we lose a lot of information on the dynamic patterns used by the cardiovascular regulation systems to adjust heart rate and blood pressure. Linear methods have not been designed to yield information on the systems' inherent dynamic properties. Nonlinear methods of signal analysis can be more useful when characterizing complex dynamics. Thus the idea of using nonlinear statistics in the analysis of heart rate and blood pressure time series data is theoretically very sound and is a challenging objective for both cardiovascular physiologists and system theoreticians. Nonlinear ...

Aims We wanted to study the effects of a 600 mg inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma. Methods In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R-R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis. Results Salbutamol significantly decreased the total and low frequency (LF) variability of R-R intervals as well as the high frequency (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation. Conclusions We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.

In the present study, a sensitive and reproducible radioreceptor assay (RRA) was used to evaluate the basic pharmacokinetic properties of glycopyrrolate, a quaternary amine with peripheral antimuscarinic activity. Based on the plasma levels after a single intravenous injection, 6 micrograms/kg (n = 6), the distribution phase half-life (2.22 +/- 1.26 s.d. min) and the elimination phase half-life (0.83 +/- 0.29 h) of glycopyrrolate were short due to the low distribution volume during the elimination phase (0.64 +/- 0.29 l/kg) and to the respectively high total plasma clearance value (0.54 +/- 0.14 l/kg/h). An intramuscular injection, 8 micrograms/kg (n = 6), was followed by a fast and predictable systemic drug absorption and clinical effects (heart rate increase, dry mouth). In this group the time to maximum plasma concentration (tmax) was 27.48 +/- 6.12 min and the maximum plasma concentration (Cmax) was 3.47 +/- 1.48 micrograms/l. After oral drug intake, 4 mg (n = 6), an apparently low and variable gastrointestinal absorption was found (tmax = 300.0 +/- 197.2 min, Cmax = 0.76 +/- 0.35 microgram/l), thus indicating that the oral route of drug administration is of no value as a routine premedication. The correlation between the plasma concentration of glycopyrrolate and the drug effects appears to be variable. Because of its sensitivity, the RRA method proved to be quite useful in evaluating the kinetics of glycopyrrolate and its relationship to various clinical effects.