Effects of Sympathetic Blockade on Cardiorespiratory Coupling via Model-Free Directional Cross-Predictability Measures

Pharmacological beta-adrenergic receptor blockade has been demonstrated to affect respiratory sinus arrhythmia (RSA). We tested the effect of beta-blocker therapy on cardiorespiratory coupling (CRC) using a cross-predictability $(C P)$ method based on k nearest neighbors. We recorded heart period (HP) and respiratory flow (RF) beat-to-beat series in 58 patients who did not undergo beta-blocker therapy (noBB; 63 ±10 yrs, 22 males, $\mathrm{VO}_{2} \mathrm{max}=16.8 \pm 4.2 \mathrm{~mL} \cdot \mathrm{~kg}^{-1} \cdot \mathrm{~min}^{-1}$) and in 55 patients who did (BB; $67 \pm 9$ yrs, 34 males, $\mathrm{VO}_{2} \mathrm{max}=17.6 \pm 6.2 \mathrm{~mL} \cdot \mathrm{~kg}^{-1} \cdot \mathrm{~min}^{-}$<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup>). We found that RSA as estimated by spectral analysis and the CP index from RF to HP was significantly increased in the BB cohort, compared to noBB, while the CP index in the reverse direction did not vary. We conclude that the pathway from RF to HP was significantly affected by sympathetic blockade, thus indicating that cardiorespiratory interactions are not exclusively under vagal control.