Paradoxical Muscle Sympathetic Reflex Activation in Human Heart Failure
Background—Muscle sympathetic activation in heart failure with reduced ejection fraction (HFrEF) has been attributed, on the basis of multi-unit recordings, to attenuated inhibitory feedback from stretch-sensitive cardiopulmonary mechanoreceptors. However, such preparations integrate two populations of single-units exhibiting directionally opposite firing when atrial pressure is perturbed. We tested the hypothesis that the proportion of single-units firing paradoxically when filling pressure increases is augmented in HFrEF.
Methods and Results—Muscle sympathetic nerve activity (MSNA) and estimated central venous pressure (eCVP) were recorded during non-hypotensive lower body negative pressure (LBNP;-10mmHg) and non-hypertensive positive pressure (LBPP;+10mmHg) in 11 treated HFrEF (LVEF 25±6% [mean±SD]) patients and 14 similarly-aged controls. Single-unit MSNA discharge was termed either 'anticipated' if firing frequency exhibited classic negative-feedback responses or 'paradoxical'. LBNP and LBPP had no heart rate, stroke volume, or blood pressure effects (P>0.05). eCVP decreased with LBNP (P<0.05), increased with LBPP (P<0.05), and was consistently higher in HFrEF (P<0.05). During LBNP the ratio of single-units with 'anticipated' and 'paradoxical' discharge was similar in HFrEF (18:7) and controls (27:5) whereas LBPP elicited 'paradoxical' reflex excitation in a greater proportion of HFrEF single-units (7:18 vs. 24:6; P=0.0001). Consequently, LBPP increased mean single-unit firing frequency (P<0.05) and did not inhibit multi-unit MSNA of HFrEF subjects (P<0.05 versus controls). Firing of 12/18 HFrEF (but no control) single-units increased during both LBPP and LBNP.
Conclusions—These findings provide the first evidence in human HFrEF for an augmented excitatory cardiopulmonary-MSNA reflex response to increased preload, incorporating two distinct single-unit populations with differing firing properties.
- central venous pressure
- heart failure
- sympathetic nerve activity
- cardiopulmonary receptors
- Received May 12, 2014.
- Revision received October 29, 2014.
- Accepted November 21, 2014.