EFFECTS OF LORAZEPAM ON CARDIAC VAGAL TONE DURING REST AND MENTAL STRESS - ASSESSMENT BY MEANS OF SPECTRAL-ANALYSIS

Dose-dependent effects of intravenously administered lorazepam on haemodynamic fluctuations were studied by means of spectral analysis, in order to elucidate sympathetic and parasympathetic components in cardiovascular control during situations of rest and mental stress after benzodiazepine administration. In a double-blind randomized cross-over study, nine male volunteers participated in two sessions: a placebo and lorazepam session. During these sessions, the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.06, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). During the placebo session the subjects received five placebo injections. For five of the nine subjects the lorazepam session was their first session. Heat rate (HR), blood pressure (BP) and respiration were recorded continuously. Power spectra were calculated per 2.5-min periods for HR, systolic (SBP) and diastolic BP (DBP). Spectral density was assessed for three frequency bands: low (LFB: 0.02-0.06 Hz), mid (MFB: 0.07-0.14 Hz) and high (HFB: 0.15-0.40 Hz). During the consecutive periods of rest, lorazepam induced a dose-dependent decrease in HR, and a dose-dependent increase in LFB, MFB and HFB power of HR, but lorazepam had no effect on BP. The effects were significant after 0.44 mg lorazepam for HR and HFB power, and after 0.94 mg lorazepam for the HR fluctuations in the LFB and MFB. Lorazepam did not influence the cardiovascular responses to the CWT. Our data underline that benzodiazepines can exert a specific influence on parasympathetic activity: lorazepam induced dose-dependent increases in cardiac vagal tone, resulting in decreased HR and increased HR variability, but only during periods of rest. The increase in vagal tone observed after low doses of lorazepam was not related to diminished sympathetic activity, altered respiration, or increased sedation

SPECTRAL-ANALYSIS OF HEMODYNAMICS DURING INFUSIONS OF EPINEPHRINE AND NOREPINEPHRINE IN MEN

Spectral analysis of fluctuations in heart rate (HR) and arterial blood pressure (BP) during a 6-h infusion of epinephrine (15 ng.kg(-1).min(-1)) or norepinephrine (30 ng.kg(-1).min(-1)) in 10 normotensive males was used to analyze effects of peripheral sympathetic nervous system activity and adrenal medullary discharge on cardiovascular variability. Power spectra were calculated for each 5-min period for HR, systolic BP, and diastolic BP to yield power values for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.40 Hz). Infusion of epinephrine and norepinephrine induced plasma concentrations of epinephrine and norepinephrine, respectively, within the high physiological range. Spectral analysis showed that low-frequency fluctuations of BP during infusions of epinephrine and midfrequency fluctuations of BP during infusion of norepinephrine changed in opposite directions. These fluctuations may represent different components of short-term cardiovascular control mechanisms during situations that mimic increased sympathoadrenal activity. No changes were observed in HR fluctuations or high-frequency fluctuations of BP after either catecholamine. Our data imply that changes in concentrations of circulating catecholamines cannot be unequivocally labeled as indexes of an altered sympathoadrenal involvement in short-term cardiovascular control