Acute volume loading exacerbates direct ventricular interaction in a model of COPD

Abstract

Volume loading increases left ventricular (LV) stroke volume (LVSV) through series interaction, but may paradoxically reduce LVSV in the presence of large increases in right ventricular (RV) afterload because of direct ventricular interaction (DVI). RV afterload is often increased in chronic obstructive pulmonary disease (COPD) as a result of pathological changes to respiratory mechanics, namely increased negative intrathoracic pressure (nITP), dynamic lung hyperinflation (DH), and increased pulmonary vascular resistance (PVR). These hallmarks of COPD negatively impact LV hemodynamics in normovolemia. However, it is unknown how these heart-lung interactions are impacted by acute volume loading. Twenty healthy subjects (23 ± 2 yr) completed the study protocol, involving acute volume loading via 20° head-down tilt (HDT) in isolation and with 1) inspiratory resistance of -20 cmH2O (HDT+nITP) and 2) nITP, expiratory resistance to induce DH and hypoxic-mediated increases in PVR (HDT+COPD model). LV volumes and geometry were assessed using triplane echocardiography. HDT significantly increased LVSV by 10 ± 10% through an 8 ± 6% increase in LV end-diastolic volume (LVEDV). HDT+nITP paradoxically decreased LVSV by 11 ± 12% and LVEDV by 6 ± 9% from supine baseline, or -14 ± 10% LVSV and -15 ± 13% LVEDV from HDT (P < 0.001). HDT+COPD model decreased LVSV (21 ± 10% and 28 ± 11%) and LVEDV (16 ± 10% and 22 ± 10%) from both supine and HDT, respectively (P < 0.001). Under all conditions, significant septal flattening (increased radius of septal curvature) occurred, indicating DVI. Thus, when RV afterload is increased and/or an external constraint to ventricular filling exists, acute volume loading appears to paradoxically reduce LVSV. These findings have important implications for understanding how volume status impacts cardiopulmonary interactions in COPD.NEW & NOTEWORTHY Volume loading may exacerbate adverse cardiopulmonary interaction in COPD; however, the mechanisms remain unclear. We found that when negative intrathoracic pressure is increased, acute volume loading paradoxically reduces stroke volume. This reduction in stroke volume is considerably greater in a model of COPD, owing to the effects of lung hyperinflation.