Impeding respiratory venous return fluctuations alters cardiorespiratory autonomic and mechanical interactions

Cardiorespiratory interactions are important for circulatory control. The act of breathing modulates cardiac output. To explore underlying mechanisms, we investigated cardiovascular responses to respiration-synchronous intermittent hypovolemia. Twelve healthy subjects underwent metronome-paced breathing synchronized with oscillatory lower body negative pressure (LBNP, 0 to -30 mmHg). Oscillations were timed to either 1) induce LBNP on inspiration (Insp+LBNP), reducing venous return and impeding mechanical effects of breathing on circulation, or 2) release LBNP on inspiration (Exp+LBNP), augmenting mechanical effects of breathing through augmented venous return fluctuations. We recorded heart rate (HR, from ECG), non-invasive finger arterial blood pressure, and estimated left cardiac stroke volume by ultrasound Doppler (l-SV). We quantified each cardiovascular variable’s respiratory-related variability by spectral analysis at peak respiratory frequency ±0.03 Hz and calculated coherence and phase angles by cross-spectral analysis. Differences between LBNP situations were tested by Wilcoxon paired signed rank test. Oscillatory LBNP elicited different responses depending on the timing of onset and release within the respiratory cycle. Variability in MAP increased fivefold during Insp+LBNP compared to Exp+LBNP, while variability in SV doubled during Exp+LBNP compared to Insp+LBNP. Variability in HR and SV showed consistent phase with respiration, independent of LBNP onset and release. MAP showed little variability when the respiratory pump was augmented, and larger variability when normal interplay between the respiratory pump and circulation was impeded. HR variability was mainly driven by respiration, despite concomitant respiration-synchronous oscillatory central hypovolemia. Respiration may have a higher potential for autonomic enforcement during cardiovascular stress such as hypovolemia.