Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure.

Abstract

Patients with heart failure have increased vascular resistance and evidence for increased neurohumoral drive. High levels of circulating norepinephrine are found in patients with heart failure, but it is not known whether they reflect increased sympathetic neural activity or result from altered synthesis, release, or metabolism of norepinephrine. We used microneurography (peroneal nerve) to directly record sympathetic nerve activity to muscle (mSNA) and also measured plasma norepinephrine levels in patients with heart failure and in normal control subjects. Our goal was to determine whether sympathetic nerve activity is increased in patients with heart failure and whether plasma norepinephrine levels correlate with levels of mSNA in heart failure. Resting muscle sympathetic nerve activity in 16 patients with moderate to severe heart failure (54 + 5 bursts/min, mean + SE) was significantly higher (p < .01) than the levels of activity in either nine age-matched normal control subjects (25 ± 4 bursts/min) or 19 "young" normal control subjects (24 + 2 bursts/min). We found a significant correlation between plasma norepinephrine levels and mSNA (r = .73, p < .05). Neither mSNA nor plasma norepinephrine levels correlated with total systemic vascular resistance, cardiac index, left ventricular ejection fraction, or heart rate. However, both mSNA and plasma norepinephrine levels showed significant positive correlations (p < .05) with left ventricular filling pressures (r = .80, mSNA vs filling pressures; r = .82, norepinephrine levels vs filling pressures) and mean right atrial pressure. The results of the study provide the first direct evidence of increased central sympathetic nerve outflow in patients with heart failure and the first direct evidence that plasma norepinephrine levels show a reasonable correlation with sympathetic nerve activity to muscle in these patients. Furthermore, the data suggest that preload is an important determinant of SNA in these patients. Circulation 73, No. 5, 913-919, 1986. A HALLMARK of advanced heart failure is high peripheral vascular resistance.' Several neurohumoral factors may contribute to the increased vascular resistance, including increased activity of the renin-angiotensin system,24 elevated levels of arginine vasopressin,5 and increased activity of the sympathetic nervous

Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.

“…[3][4][5][6][12][13][14][15][16] These uniform findings of sympathetic activation directed to tissues governed by the baroreflexes have prompted the concept that impaired baroreflex restraint underlies sympathetic activation. It is unknown if increased sympathetic neural outflow in heart failure is limited to regions governed by the baroreflexes or is generalized to all tissues -a distinction with mechanistic implications.…”

Arterial baroreflex function and cardiovascular variability: interactions and implications

“…In these patients, despite direct evidence of high levels of sympathetic activation (increased cardiac and total norepinephrine spillover and MSNA) (36,59), there is a blunting or absence of the LF component of R-R and SNA (83,116). The observed dissociation between sympathetic drive and LF power in the power spectra of cardiovascular variability implies that the traditional paradigm linking increased sympathetic drive to increased LF power in normal subjects cannot simply be extrapolated to include pathological conditions such as severe heart failure, where all homeostatic mechanisms are mobilized at close to maximum levels with little or no reserve to maintain variability.…”

Prognostic Implications of Relations of Left Ventricular Systolic Dysfunction with Body Composition and Myocardial Energy Expenditure: The Strong Heart Study

“…39 Faster heart rate in our participants with EF less than 45% suggests sympathetic overactivity with moderately or severely depressed LV systolic function. However, our findings are made more generally applicable because they were obtained in a population-based sample of adults, from which severe LV dysfunction with acute CHF was excluded, thereby largely excluding cardiac cachexia.…”