Efferent sympathetic nerve discharge is both gated to the cardiac cycle and inhibited by afferent input from cardiac, aortic, and carotid mechanoreceptors stimulated by rhythmic atrial and conduit artery distension. In patients with chronic heart failure as a consequence of impaired systolic function, both this gating and the blood pressure–muscle sympathetic nerve activity (MSNA) relationship are preserved.1–3 The evolution of mechanical left ventricular support from devices that generate a pulse wave to those that propel blood continuously thus raises a number of intriguing questions about the body’s adaptation to this alien physiology: What effect does short- or long-term diminution or loss of arterial pulse pressure have on the neural regulation of the heart and circulation by the baroreceptor reflex? What impact do such changes have on endothelial biology, autoregulation of regional blood flow, and tissue or organ perfusion? Article see p 2316 The first of these questions is the subject of a contribution from the Levine laboratory to the present issue of Circulation .4 These investigators focused their attention on the effect of acute alterations in mean and pulse pressures on 1 efferent limb of the arterial baroreceptor reflex arc, postganglionic sympathetic discharge to calf skeletal muscle, which they recorded directly from the fibular nerve. In a previously published experiment by this group, MSNA was recorded under 2 conditions, supine rest and 60° head-up tilt, in 6 patients with implanted left ventricular assist devices (LVADs) providing pulsatile flow and from 11 with nonpulsatile LVADs. In those with nonpulsatile compared with pulsatile LVADs, MSNA was 80% higher at rest and 70% higher during tilt, a difference these investigators attributed to diminished arterial mechanoreceptor stretch.5 Cornwell et al4 now report the findings of a protocol involving 13 patients with implanted Heartmate II continuous axial-flow devices designed …