Scattergrams and mean ± standard error for muscle sympathetic nerve activity (MSNA) (bursts/100 cardiac cycles) in treated heart failure (HF) patients with (SD) and without sleep-disordered breathing (NSD) (8), compared with age-matched healthy laboratory control subjects. MSNA is increased significantly when apnea coexists with HF (p = 0.005), whereas MSNA in treated HF patients without apnea is similar to MSNA in control subjects.

Convergence of afferent input from 2 sets of reflexes (e.g., HF and sleep apnea) eliciting directionally similar excitatory effects on MSNA may summate and interact centrally through mutual inhibition, addition, or mutual facilitation. The difference in MSNA recorded during wakefulness between HF patients with and without obstructive sleep apnea (OSA) (8) is eliminated when OSA is abolished (79). Thus, these 2 stimuli appear to interact by summation. Adapted from Figure 2 in Abboud and Thames (80). Abbreviations as in Figure 1.

As systolic dysfunction develops, inhibitory input from primarily ventricular mechanoreceptors decreases (thin line), whereas efferent sympathetic nerve modulation by the arterial baroreceptor and pulmonary stretch reflexes is preserved. Vagal modulation of HR and efferent vagal and sympathetic heart rate (HR) responses to arterial baroreflex perturbations are attenuated. Excitatory (+) inputs from an atrial reflex activated by increases in cardiac filling pressures, and from chemically sensitive ventricular afferent nerve endings, triggered by ischemia, add to augmented sympathoexcitatory input from arterial chemoreceptors and from exercising skeletal muscle (thick lines). Renal afferent nerves (not shown) may also elicit sympathoexcitation. Central excitatory mechanisms (downward arrow) include an angiotensin II-AT₁ receptor-NADPH-superoxide axis, and sleep apnea. Potential efferent mechanisms include pre-/junctional facilitation of norepinephrine (NE) release and altered NE uptake. Early systolic dysfunction is characterized by a selective increase in cardiac NE release and a reduction in tonic and reflex vagal HR modulation, whereas in advanced heart failure, there is a generalized increase in sympathetic nerve traffic (thick arrow shafts, thick lines), blunted vagal (thin line) and sympathetic HR modulation, and impairment of the reflex sympathetic regulation of vascular resistance. Ach = acetylcholine; CNS = central nervous system; E = epinephrine.