A central γ-aminobutyric acid mechanism in cardiac vagal control in man revealed by studies with intravenous midazolam

Abstract

1. Animal studies show that cardiac vagal tone can be modified by gamma-aminobutyric acid neurons acting at several sites in the central nervous system. The present study has attempted to determine whether similar control exists in humans by using midazolam, a benzodiazepine. Benzodiazepines exert their main actions on the central nervous system by interacting co-operatively at the gamma-aminobutyric acid receptor. 2. Twenty patients took part in the study before undergoing cardiac catheterization. After resting for 20 min in a semi-supine position on a couch, ECG, blood pressure and respiration were recorded for 5-min periods with either controlled (fixed) or free respiration. During this time a baroreceptor sensitivity test was conducted. 3. Doses of 1 mg and 5 mg of midazolam were administered intravenously. 4. Five-minute segments of data, before and after midazolam, were subjected to power spectral and time-domain analysis. 5. Midazolam caused a decrease in the high-frequency and an increase in the low-frequency components of the power spectral density plot, and in addition reduced the mean R-R interval and R-R variability expressed as the interquartile difference, and pNN50. There were no significant changes in the sensitivity of the baroreflex or in the systolic, diastolic and average blood pressures. 6. This decrease in variability of heart period, particularly at a controlled respiratory frequency, strongly suggests that cardiac vagal tone in man can be regulated by gamma-aminobutyric acid neurons.

GABAergic mechanisms involved in the vagally mediated heart rate response to muscle contraction as revealed by studies with benzodiazepines

“…Previously we have shown that there is a GABA A -mediated suppression of cardiac vagal tone in man [9][10][11], which is in agreement with existing animal data [13,21]. In the present study it was found that resting cardiac vagal tone was little affected by 10 mg oral diazepam,as has been noted previously [25], unlike the dramatic reductions seen with the more potent benzodiazepine midazolam [11].…”

“…In the present study it was found that resting cardiac vagal tone was little affected by 10 mg oral diazepam,as has been noted previously [25], unlike the dramatic reductions seen with the more potent benzodiazepine midazolam [11]. The results of time-and frequency-domain analysis also show no significant differences between diazepam and placebo.…”

Vigabatrin Decreases Cholecystokinin-Tetrapeptide (CCK-4) Induced Panic in Healthy Volunteers

“…It is well known that the activity of the HPA system is inhibited by GABAergic mechanisms (Holsboer 1998). In contrast, heart rate has been shown to increase following treatment with benzodiazepines in rats (Castro et al 1999) and humans (Farmer et al 1998) which is in line with the differential effects of vigabatrin on HPA system activity and heart rate.…”

Comparison of the effects of propofol and midazolam on the cardiovascular autonomic nervous system during combined spinal and epidural anesthesia

“…It has been reported that midazolam decreased both LF and HF in HRV without changes in LF/HF ratio [12] and depressed sympathetic activity to produce a vagotonic condition during spinal anesthesia [2]. The effects of benzodiazepine may be mediated by the modulation of GABAergic tone in the brain stem [13], which is involved in the endogenous regulation of SAP and vagal outflow to the heart and respiratory tract [14]. In this study, the HF component in HRV and SAPV with midazolam or propofol was thought to be secondary to the activities of the coupled cardiorespiratory neurons and ventilatory periodicity.…”