Time-Domain HRV During Slow Breathing Tracks Vagal, Not Sympathetic, Modulation: A Pharmacological Challenge.

Time-domain heart rate variability (HRV) metrics are widely used to infer autonomic function and remain valid indicators of vagal influence during a wide range of breathing conditions; however, their specificity to parasympathetic modulation under slow-paced breathing remains unclear. Building on prior pharmacological work, this study tested whether RMSSD, pNN50, SDNN, as well as exploratory Toichi nonlinear metrics index vagal activity during respiratory and pharmacological manipulation. Six healthy adults completed eleven 1-minute breathing trials (4–9 bpm) following double-blind administration of saline, esmolol (β-adrenergic blockade), or glycopyrrolate (muscarinic blockade). Parasympathetic blockade significantly suppressed all HRV metrics and increased heart rate, whereas sympathetic blockade had no effect. Breathing rate, drug condition, and their interaction were non-significant, indicating that drug effects on HRV were consistent across respiratory conditions. These findings support the interpretation of time-domain HRV indices as predominantly parasympathetic markers, rather than sympathetic, across paced breathing in controlled laboratory settings.