LORAZEPAM REDUCES CARDIAC VAGAL MODULATION IN NORMAL SUBJECTS

Benzodiazepines are frequently administered postmyocardial infarction, but their effect on heart period variability (HPV), a prognostic inde x of sudden arrhythmogenic death, is unclear. In fact, in both humans and animals, previous studies utilizing acute intravenous doses yielde d mixed results. We hypothesized that lorazepam (LZ), by potentiating gamma-aminobutyric acid-A-ergic inhibition of preganglionic vagal neur ons projecting to the heart, would reduce cardiac vagal modulation. We therefore tested LZ's effect on HPV over 24 hours of normal physiolog ic activity in human volunteers in the presence of steady-state LZ. A double-blind, randomized, placebo-controlled study was conducted. Seve n healthy subjects received LZ or placebo for 1 week, I week taper, th en crossed over. Electrocardiogram recordings measured HPV after the a dministration of drug and placebo for 24 hours. LZ increased mean hear t rate by 8% (p < 0.002), decreased the standard deviation of R-R inte rvals by 9% (p < 0.05), decreased the percent differences between adja cent normal PL-R intervals > 50 msec by 30% (p < 0.002), decreased the root-mean-square successive difference by 17% (p < 0.02), and decreas ed the natural logarithm of high-frequency power by 6% (p < 0.03). The significant heart rate increase and HPV decreases demonstrate vagolyt ic effects of LZ in healthy subjects during 24 hours of normal physiol ogic activity.