, Volume 114, Issue 1, pp 81-89

Effects of lorazepam on cardiac vagal tone during rest and mental stress: assessment by means of spectral analysis

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Abstract

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.