Rapid fall in sympathetic nerve hyperactivity in patients with heart failure after cardiac transplantation.

BACKGROUND: Severe heart failure is associated with an intense sympathetic nerve hyperactivity. After cardiac transplantation, neurochemical studies have indicated a normalization of sympathetic outflow. Intraneural recordings have, however, yielded varying results; both a normalization and a remaining hyperactivity have been obtained in cardiac transplant recipients, the latter being attributed to cyclosporine treatment. METHODS AND RESULTS: To circumvent the methodologic variation associated with different patient groups in cross-sectional studies, a longitudinal study design was employed in this study. Intraneural recordings of muscle sympathetic nerve activity in 21 heart failure patients were performed before, and repeatedly during the first year after, heart transplantation. Before surgery, muscle sympathetic nerve activity was augmented in all patients (78 +/- 4 bursts/min, 90 +/- 2 bursts/100 heartbeats). Both muscle sympathetic nerve activity burst frequency (burst/minute) and burst incidence (bursts/100 heartbeats) decreased rapidly following surgery. One month after surgery, burst frequency was reduced by 35% (51 +/- 5 bursts/min P < .05), whereas burst incidence decreased by 32% (61 +/- 5 bursts/100 heartbeats, P < .05). This decrease remained unchanged up to 1 year after surgery. The fall in posttransplant muscle sympathetic nerve activity was similar in transplant recipients who developed hypertension during the course of the study (n = 12) and those who remained normotensive (n = 9). CONCLUSIONS: The sympathoexcitation recorded in patients with heart failure was rapidly and substantially reduced after cardiac transplantation despite cyclosporine treatment, most likely reflecting improved central and peripheral hemodynamics.

Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure.

BACKGROUND: Previous studies with radiotracer methods have indicated increases in cardiac norepinephrine (NE) and renal NE spillover in patients with severe congestive heart failure (CHF). However, data on the regional sympathetic profile in early stages of CHF are limited. In this study, sympathetic function in the heart, kidneys, and skeletal muscle was evaluated in patients with mild-to-moderate CHF and compared with that in patients with severe CHF and healthy subjects. METHODS AND RESULTS: Total body and regional NE spillover from the heart and kidney was assessed with isotope dilution with steady state infusions of [3H]NE. Sympathetic nerve traffic to the skeletal muscle vascular bed (MSA) was recorded intraneurally. Cardiac NE spillover in patients with mild-to-moderate CHF (n = 21) was increased threefold versus that in healthy subjects (n = 12, P < .05), whereas total body and renal NE spillover and MSA did not differ from those in healthy subjects. In the severe CHF group (n = 12), cardiac NE spillover was increased fourfold (P < .05), and total body and renal NE spillover and MSA were high compared with both mild-to-moderate CHF subjects and healthy subjects (P < .05 for both). Fractional extraction of [3H]NE across the heart was reduced by approximately 40% in both CHF groups versus control subjects (P < .05). CONCLUSIONS: These results indicate a selective increase in cardiac adrenergic drive (increased amounts of transmitter available at neuroeffector junctions) in patients with mild-to-moderate CHF. This increase appears to precede the augmented sympathetic outflow to the kidneys and skeletal muscle found in advanced CHF.