Peripheral sympathetic control during dobutamine infusion: effects of aging and heart failure

Objectives We assessed the effects of beta-adrenergic agonism on muscle sympathetic nerve activity (MSNA) in patients with congestive heart failure (CHF) and young and matched controls. Background Myocardial response to beta-adrenergic stimulation decreases with aging and with CHF. Methods In CHF patients, we measured cardiac hemodynamics and MSNA (microneurography) before, with short-term (n = 5), and after 48-h (n = 9) of dobutamine infusion (10 μg/kg/min). In eight young controls and nine controls matched to the CHF patients, we measured cardiac hemodynamics and MSNA during randomized short-term dobutamine (10 μg/kg/min) and placebo infusions. Results In CHF patients, short-term dobutamine infusion did not modify mean blood pressure (MBP), MSNA, or heart rate (HR). Moreover, 48-h dobutamine infusion increased cardiac index (3.1 ± 0.2 vs. 2.2 ± 0.2 l/min/m2, p = 0.006), decreased mean pulmonary pressure (28 ± 7 vs. 38 ± 7 mm Hg, p = 0.0001) and peripheral resistance (1,099 ± 112 vs. 1,759 ± 263, p = 0.03), but did not change MBP, HR, or MSNA in the patients. In matched controls, dobutamine increased HR (87 ± 5 vs. 65 ± 2 beats/min, p = 0.0009) but did not change MBP or MSNA. In young controls, dobutamine increased MBP (102 ± 2 vs. 90 ± 2 mm Hg, p = 0.0003) and decreased MSNA (28 ± 5 vs. 35 ± 3 bursts/min, p = 0.03) but did not change HR (p = 0.054). In the controls, the largest increases in MBP with dobutamine were associated with the most marked reductions in MSNA (r = −0.49, p = 0.04) and the smallest increases in HR (r = −0.70, p = 0.001). Conclusions Arterial baroreceptor activation during increases in MBP inhibits MSNA and limits the HR response to dobutamine in controls. This mechanism, together with peripheral vasodilation, probably contributes to the absence of peripheral sympathetic withdrawal despite substantial hemodynamic improvements in CHF patients.