Standardized Carotid Sinus Stimulation Versus Sham: A Pilot Randomized Controlled Trial Assessing Acute Autonomic and Hemodynamic Responses in Healthy Adults

ABSTRACT
Background: The carotid sinus baroreflex exerts rapid, reflexive control over heart rate and arterial pressure. Although
carotid sinus massage is used diagnostically and therapeutically in select arrhythmias, its immediate autonomic and
hemodynamic effects under a standardized protocol have not been tested in a randomized trial of healthy adults.
Objective: To compare the acute autonomic and hemodynamic responses of targeted carotid sinus stimulation versus
sham stimulation in healthy volunteers.
Methods: We conducted a single-center, parallel-group, 1:1 randomized, outcome-assessor–blinded trial. Thirty healthy
adults (22–35 years) were randomized to targeted carotid sinus stimulation (intervention; n=15) or sham stimulation
(control; n=15). Heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), and heart rate variability (HRV;
RMSSD, HF power) were obtained at baseline, during stimulation and two minutes post-intervention. Analysis used
SPSS-style procedures (intention-to-treat, paired t-tests, independent t-tests of change-scores and repeated-measures
ANOVA). Primary outcome was change in HR during stimulation; secondary outcomes were SBP, DBP and HRV.
Results: Compared with control, the intervention produced greater reductions in HR (−7.6±2.4 vs −0.9±1.9 bpm;
p<0.001) and SBP (−8.8±3.4 vs −1.3±2.7 mmHg; p<0.001), with modest DBP reduction (−4.7±2.3 vs −0.6±2.1 mmHg;
p<0.001). RMSSD increased by 18.9% in the intervention group versus 2.1% in control (p=0.002). No adverse events
occurred.
Conclusion: In healthy adults, standardized targeted carotid sinus stimulation acutely augments parasympathetic
activity and reduces heart rate and arterial pressure compared with sham. These findings support feasibility and inform
the design of confirmatory trials in patient populations.
Keywords: Carotid sinus, baroreflex, autonomic modulation, heart rate variability, randomized controlled trial,
physiotherapy, cardiovascular reflexes.
How to cite this article: Shanmugam A, Pannir Selvam SP, Subramanian SS, Suganthirababu P. Standardized Carotid
Sinus Stimulation Versus Sham: A Pilot Randomized Controlled Trial Assessing Acute Autonomic and Hemodynamic
Responses in Healthy Adults. Int J Drug Deliv Technol. 2026;16(48s): 547-552. DOI: 10.25258/ijddt.16.48s.53