Cardiac and systemic sympathetic activity in response to clonidine in human heart failure

Objectives. We studied the effects of clonidine on cardiac sympathetic acti vity and left ventricular function in patients with congestive heart failur e (CHF). Background. Sympathetic activation has major prognostic implications in pat ients with heart failure. Clonidine, an imidazoline and alpha, receptor ago nist, has been shown to cause a reduction in generalized sympathetic activi ty. Methods. Nine patients with CHF (left ventricular ejection fraction 22 +/- 4% [mean +/- SEM]) received a 50 mu g and 100 mu g bolus of clonidine intra venously. Study measurements included right and left heart hemodynamics, ca rdiac output, rate of rise in left ventricular peak positive pressure (LV dP/dt) and tau, along with cardiac and total body norepinephrine spillover . The radiotracer method was used for calculation of norepinephrine spillov er. Results. Right and left heart filling pressures did not change in response to either dose of clonidine. Mean arterial pressure fell after the second d ose of clonidine, from 94 +/- 8 to 82 +/- 6 mm Hg (p < 0.05). The LV + dP/d t was reduced from 737 +/- 53 to 629 +/- 43 mm Hg/s (p < 0.05). Clonidine a lso caused a significant increase in tau, as measured by the method of Weis s (65 +/- 3 vs. 74 +/- 4 ms, p < 0.01) and the direct pressure half time te chnique (48 +/- 2 vs. 54 +/- 3 ms, p < 0.01), Cardiac norepinephrine spillo ver fell from 121 +/- 29 to 52 +/- 20 pmol/min in response to 100 mu g of c lonidine (p < 0.01 vs. control). Conclusions. Despite a significant fall in arterial pressure, clonidine cau sed a marked reduction in sympathetic activity directed at the heart. The n egative inotropic and lusitropic effects appear to be secondary to this red uction in sympathetic drive. Because increased cardiac and generalized symp athetic activity are strong predictors of an adverse outcome in patients wi th CHF, the role of centrally active sympathoinhibitory agents in the thera py of CHF deserves further exploration. (C) 1998 by the American College of Cardiology.