Effect of sympathoinhibition on exercise performance in patients with heart failure

In patients with heart failure, excessive sympathetic activation during exercise could interfere with exercise performance by impairing arteriolar dilation in working muscle and by adversely altering skeletal muscle metabolic behavior. To test this hypothesis, we examined the effect of sympathoinhibition with clonidine, a central sympatholytic agent, on skeletal muscle blood flow and metabolism in patients with heart failure.

Swan-Ganz and femoral venous catheters were inserted in 20 patients with chronic heart failure and exercise intolerance (peak exercise VO2 = 9.3 +/- 1.4 [SEM] mL.min-1.kg-1). Central hemodynamic measurements, leg blood flow determined by thermodilution, and systemic and leg metabolic parameters were measured during maximal treadmill exercise before and 2 hours after clonidine 2 micrograms/kg IV (n = 15) or 0.9% normal saline (n = 5). During-control exercise before the administration of clonidine, leg blood flow increased from 0.3 +/- 0.1 to 1.8 +/- 0.2 L/min and plasma norepinephrine increased from 485 +/- 61 to 2155 +/- 186 pg/mL (both P < .01). Treatment with clonidine markedly suppressed norepinephrine levels during exercise (matched peak exercise workload: control, 2137 +/- 187 versus clonidine, 1430 +/- 161 pg/mL), increased leg blood flow (control, 1.8 +/- 0.2 versus clonidine, 2.3 +/- 0.4 L/min), reduced systemic oxygen consumption (control, 1002 +/- 70 versus clonidine, 966 +/- 68 mL/min), reduced pulmonary artery lactate concentration (control, 3.2 +/- 0.3 versus clonidine, 2.6 +/- 0.2 mEq/L), and decreased minute ventilation (control, 39.7 +/- 2.1 versus clonidine, 34.9 +/- 2.4 L/min) (all P < .05).

These findings suggest that sympathetic activation during exercise reduces leg blood flow, increases muscle glycolysis, and decreases muscle efficiency in patients with heart failure.