Selegiline improves cardiac sympathetic terminal function and beta-adrenergic responsiveness in heart failure

Selegiline is a centrally acting sympatholytic agent with neuroprotective p roperties. It also has been shown to promote sympathetic reinnervation afte r sympathectomy. These actions of selegiline may be beneficial in heart fai lure that is characterized by increased sympathetic nervous activity and fu nctional sympathetic denervation. Twenty-seven rabbits with rapid cardiac p acing (360 beats/min, 8 wk) and twenty-three rabbits without pacing were ra ndomly assigned to receive selegiline (1 mg/day, 8 wk) or placebo. Rapid pa cing increased plasma norepinephrine (NE) and decreased left ventricular fr actional shortening, baroreflex sensitivity, cardiac sympathetic nerve term inal profiles, cardiac NE uptake activity, and myocardial beta-adrenoceptor density. Selegiline administration to animals with rapid ventricular pacin g attenuated the increase in plasma NE and decreases in fractional shorteni ng, baroreflex sensitivity, sympathetic nerve profiles, NE uptake activity and beta-adrenoceptor density. Thus selegiline appears to exert a sympathol ytic and cardiac neuroprotective effect in pacing-induced cardiomyopathy. T he effects are potentially beneficial because selegiline not only improves cardiac function but also increases baroreflex sensitivity in heart failure .