Mechanisms of causal interaction between short-term RR interval and systolic arterial pressure oscillations during orthostatic challenge

The transition from the supine to the upright position requires a reorganization of the mechanisms of cardiovascular control that, if not properly accomplished, may lead to neurally mediated syncope. We investigated how the patterns of causality between systolic arterial pressure (SAP) and cardiac RR interval were modified by prolonged head-up tilt using a novel nonlinear approach based on corrected conditional entropy (CCE) compared with the standard approach exploiting the cross-correlation function (CCF). Measures of coupling strength and delay of the causal interactions from SAP to RR and from RR to SAP were obtained in 10 patients with recurrent, neurally mediated syncope (RNMS) and 10 healthy control (CO) subjects in the resting supine position (su) and after head-up tilting during early (et; ~2 min) and late (lt; ~15 min or before presyncope) epochs of upright posture. Main results were that 1) the coupling strength from SAP to RR increased significantly from su to et in both groups; by contrast, upon lt, the coupling strength was kept high in CO subjects and dropped to low values in RNMS patients; 2) in RNMS patients, the delay from SAP to RR was higher than in healthy controls and increased moving from et to lt. Although these trends were evident using the CCE approach, statistical significance was not attained using the CCF approach. These results indicate the necessity of dissecting causality between RR and SAP to properly assess directional mechanisms from the closed-loop cardiovascular regulation and suggest a weakened and slowed baroreflex as a major mechanism involved in the cardiovascular impairment associated to neurally mediated syncope.