A CENTRAL GAMMA-AMINOBUTYRIC-ACID MECHANISM IN CARDIAC VAGAL CONTROL IN MAN REVEALED BY STUDIES WITH INTRAVENOUS MIDAZOLAM

1. Animal studies show that cardiac vagal tone can be modified by gamm a-aminobutyric acid neurons acting at several sites in the central ner vous system. The present study has attempted to determine whether simi lar control exists in humans by using midazolam, a benzodiazepine. Ben zodiazepines exert their main actions on the central nervous system by interacting cooperatively at the gamma-aminobutyric acid receptor. 2. Twenty patients took part in the study before undergoing cardiac cath eterization. After resting for 20 min in a semi-supine position on a c ouch, EGG, blood pressure and respiration were recorded for 5-min peri ods with either controlled (fixed) or free respiration. During this ti me a baroreceptor sensitivity test was conducted. 3. Doses of 1 mg and 5 mg of midazolam were administered intravenously. 4. Five-minute seg ments of data, before and after midazolam, were subjected to power spe ctral 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 inte rval and R-R variability expressed as the interquartile difference, an d pNN50. There were no significant changes in the sensitivity of the b aroreflex or in the systolic, diastolic and average blood pressures. 6 . This decrease in variability of heart period, particularly at a cont rolled respiratory frequency, strongly suggests that cardiac vagal ton e in man can be regulated by gamma-aminobutyric acid neurons.