Respiratory rate and minute ventilation independently modulate cardiovascular and autonomic responses in healthy...

Respiration influences autonomic and cardiovascular function, yet the independent contributions of respiratory rate (RR) and minute ventilation (MV) remain unclear. We investigated how RR and MV independently and interactively affect cardiovascular and autonomic responses using a 2 × 2 controlled-breathing design in 19 healthy adults (24.6 ± 1.2 years): spontaneous RR versus slow RR (6 breaths/min), combined with MV at 100% versus 180% of resting baseline. We recorded heart rate (HR), stroke volume (SV), cardiac output (CO), and heart rate variability (SDNN). Elevating MV to 180% significantly increased HR (5-8%) and CO (6-12%) across both respiratory rates (p < 0.01), whereas changing RR alone at constant MV produced no significant cardiovascular effects. Temporal analysis revealed a mechanistically biphasic CO response: the early rise (minutes 1-2) was driven by increasing SV while HR remained stable, whereas the sustained later elevation was driven by progressive HR increases as SV declined. Slow RR increased HRV by 75-86% (p < 0.01), indicating increased overall heart rate variability, which may reflect enhanced autonomic flexibility. Notably, combining slow RR with high MV produced concurrent increases in both HR and HRV, diverging from the typical inverse HR-HRV relationship and suggesting sympathetic-parasympathetic co-activation. These findings demonstrate a clear bifurcation in cardiorespiratory control, identifying minute ventilation as the primary driver of short-term systemic cardiovascular modulation. In contrast, respiratory rate remains the dominant determinant of cardiac autonomic regulation (HRV).