Lorazepam reduces cardiac vagal modulation in normal subjects

Benzodiazepines are frequently administered postmyocardial infarction, but their effect on heart period variability (HPV), a prognostic index of sudden arrhythmogenic death, is unclear. In fact, in both humans and animals, previous studies utilizing acute intravenous doses yielded mixed results. We hypothesized that lorazepam (LZ), by potentiating gamma-aminobutyric acid-A-ergic inhibition of preganglionic vagal neurons projecting to the heart, would reduce cardiac vagal modulation. We therefore tested LZ's effect on HPV over 24 hours of normal physiologic activity in human volunteers in the presence of steady-state LZ. A double-blind, randomized, placebo-controlled study was conducted. Seven healthy subjects received LZ or placebo for 1 week, I week taper, then crossed over. Electrocardiogram recordings measured HPV after the administration of drug and placebo for 24 hours. LZ increased mean heart rate by 8% (p < 0.002), decreased the standard deviation of R-R intervals by 9% (p < 0.05), decreased the percent differences between adjacent normal PL-R intervals > 50 msec by 30% (p < 0.002), decreased the root-mean-square successive difference by 17% (p < 0.02), and decreased the natural logarithm of high-frequency power by 6% (p < 0.03). The significant heart rate increase and HPV decreases demonstrate vagolytic effects of LZ in healthy subjects during 24 hours of normal physiologic activity.