Abstract
Introduction Baroreflex function plays a critical role in cardiovascular regulation, with carotid baroreceptors exerting a significant influence on autonomic and hemodynamic responses. While prior studies have suggested functional asymmetry between the left and right carotid baroreceptors, the findings remain inconsistent. These inconsistencies stem from several limitations, including small sample sizes, reliance on animal models, and inadequate consideration of confounding factors such as respiratory influence and baseline autonomic tone. A major barrier to conducting well-controlled human studies is the lack of non-invasive methods capable of delivering precise, side-specific baroreceptor stimulation. To address these gaps, we introduce a novel, non-invasive, digitally controlled paired neck chamber device that enables accurate, graded unilateral and bilateral stimulation using both negative and positive pressure, thereby overcoming several limitations of earlier techniques. The objective of this study is to evaluate the autonomic responses (RR interval (RRI) and heart rate) and hemodynamic responses (systolic blood pressure (SBP) and diastolic blood pressure (DBP)) to left, right, and bilateral carotid baroreceptor stimulation using graded negative and positive pressure stimuli. The study also seeks to evaluate baroreflex sensitivity (BRS) and the dose-response relationships under various stimulation conditions. Methods We conducted a prospective interventional study at All India Institute of Medical Sciences (AIIMS) Nagpur in collaboration with the Indian Institute of Technology (IIT) Jodhpur, involving 108 healthy young adults (57 males and 51 females). Participants had a neck ultrasound to find the carotid sinus, and then they were exposed to controlled pressure changes (from -100 mmHg to +100 mmHg) on the left, right, or both carotid sinuses. ECG and continuous blood pressure monitoring were used to evaluate autonomic and hemodynamic responses. Repeated measures using ANOVA analyzed variations in autonomic and hemodynamic responses among different stimulation sites. Nonlinear regression was employed to model dose-response relationships, while Friedman and Wilcoxon signed-rank tests were utilized to compare BRS gain. Multiple linear regression analyzed the relationships between BRS and markers of autonomic tone. Results Bilateral stimulation elicited the strongest bradycardic response (RRI up to 0.41 s) and more stable tachycardia under positive pressure compared to unilateral stimulation. Left-sided stimulation had a greater cardiac effect, while right-sided stimulation showed stronger blood pressure modulation (SBP and DBP fall up to 24.35 mmHg and 15.78 mmHg). BRS did not differ significantly across conditions, and the non-additive bilateral response suggests central integration. Conclusions This study provides new insights into carotid baroreceptor asymmetry, demonstrating that bilateral stimulation enhances autonomic modulation, while unilateral stimulation exhibits differential cardiac and blood pressure effects. These findings have clinical implications for baroreflex activation therapy (BAT) in conditions such as hypertension and heart failure. Future research can explore long-term adaptations, neuroplasticity, and central baroreflex processing to refine therapeutic strategies.