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CLINICAL STUDIES

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

^a Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Manuscript received September 11, 1998; accepted September 24, 1998.

Address for correspondence: Dr. John D. Parker, Mount Sinai Hospital, Division of Cardiology, 600 University Avenue, Suite 1609, Toronto, Ontario, Canada M5G-1X5
jdp{at}inforamp.net

Objectives. We studied the effects of clonidine on cardiac sympathetic activity and left ventricular function in patients with congestive heart failure (CHF).

Background. Sympathetic activation has major prognostic implications in patients with heart failure. Clonidine, an imidazoline and alpha₂-receptor agonist, has been shown to cause a reduction in generalized sympathetic activity.

Methods. Nine patients with CHF (left ventricular ejection fraction 22 ± 4% [mean ± SEM]) received a 50 µg and 100 µg bolus of clonidine intravenously. Study measurements included right and left heart hemodynamics, cardiac 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 spillover.

Results. Right and left heart filling pressures did not change in response to either dose of clonidine. Mean arterial pressure fell after the second dose of clonidine, from 94 ± 8 to 82 ± 6 mm Hg (p < 0.05). The LV + dP/dt was reduced from 737 ± 53 to 629 ± 43 mm Hg/s (p < 0.05). Clonidine also caused a significant increase in tau, as measured by the method of Weiss (65 ± 3 vs. 74 ± 4 ms, p < 0.01) and the direct pressure half-time technique (48 ± 2 vs. 54 ± 3 ms, p < 0.01). Cardiac norepinephrine spillover fell from 121 ± 29 to 52 ± 20 pmol/min in response to 100 µg of clonidine (p < 0.01 vs. control).

Conclusions. Despite a significant fall in arterial pressure, clonidine caused a marked reduction in sympathetic activity directed at the heart. The negative inotropic and lusitropic effects appear to be secondary to this reduction in sympathetic drive. Because increased cardiac and generalized sympathetic activity are strong predictors of an adverse outcome in patients with CHF, the role of centrally active sympathoinhibitory agents in the therapy of CHF deserves further exploration.

Abbreviations and Acronyms   CHF = congestive heart failure   +dP/dt = rate of rise in left ventricular peak positive pressure   ECG = electrocardiogram   HPLC = high performance liquid chromatography   LV = left ventricular   TL = time constant of isovolumic relaxation   T1/2 = pressure half-time

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