NORMALIZATION OF TOTAL-BODY AND REGIONAL SYMPATHETIC HYPERACTIVITY INHEART-FAILURE AFTER HEART-TRANSPLANTATION

Background: Sympathetic nerve activity is increased in patients with s evere heart failure. Whether this intense sympathoexcitation is normal ized after heart transplantation, despite cyclosporine A treatment, is still unsettled. In the present study, regional sympathetic function in 12 patients with severe heart failure, awaiting heart transplantati on, was compared with that in 15 heart transplant recipients and 12 he althy subjects. Methods: Total and regional sympathetic activity in th e heart and kidney were evaluated with isotope dilution, using steady- state infusion of [H-3] norepinephrine. Sympathetic nerve traffic to s keletal muscle vascular bed was recorded intraneurally with microneuro graphy. Results: Total body, cardiac, and renal norepinephrine spillov ers were high in the heart failure group (6799 +/- 455, 385 +/- 74, an d 1554 +/- 114 pmol/min, respectively) as was muscle sympathetic nerve activity (82 +/- 5 bursts/min). Transplant recipients showed a marked reduction of total body (3200 +/- 307 pmol/min) and renal (747 +/- 16 9 pmol/min) norepinephrine spillovers and sympathetic nerve firing to skeletal muscle (22 +/- 6 bursts/min), none of which differed Dom heal thy subjects. Conclusions: The augmentation of total body and regional sympathetic outflow to the kidney and skeletal muscle vascular beds, associated with a failing heart, was normalized after transplantation. Thus, sympathoexcitation in heart failure is reversible. Furthermore, because all heart transplant recipients received cyclosporine A, the findings do not support the concept that cyclosporine-induced hyperten sion is mediated by increased sympathetic nerve activity.