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Cardiac and systemic sympathetic activity in response to clonidine in human heart failure
E R Azevedo1, G E Newton, J D Parker
1Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Insights
Clonidine significantly reduced cardiac sympathetic activity in patients with congestive heart failure (CHF), leading to negative inotropic and lusitropic effects. This suggests a potential role for centrally acting sympathoinhibitory agents in CHF therapy.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Sympathetic nervous system overactivation is a key factor in the poor prognosis of heart failure.
- Clonidine, an alpha2-adrenergic agonist, is known to reduce generalized sympathetic activity.
Purpose of the Study:
- To investigate the impact of clonidine on cardiac sympathetic activity and left ventricular function in patients diagnosed with congestive heart failure (CHF).
Main Methods:
- Nine patients with CHF received intravenous clonidine (50 mcg and 100 mcg).
- Hemodynamic parameters, cardiac output, left ventricular contractility (LV + dP/dt), relaxation (tau), and norepinephrine spillover were measured.
- Norepinephrine spillover was quantified using a radiotracer method.
Main Results:
- Clonidine administration led to a decrease in mean arterial pressure and a significant reduction in LV + dP/dt, indicating negative inotropic effects.
- The drug also increased tau, suggesting impaired left ventricular relaxation (lusitropic effect).
- Cardiac norepinephrine spillover markedly decreased after 100 mcg of clonidine, signifying reduced cardiac sympathetic activity.
Conclusions:
- Clonidine effectively reduces cardiac sympathetic activity in CHF patients, despite causing a drop in blood pressure.
- Observed negative inotropic and lusitropic effects are likely consequences of decreased sympathetic drive to the heart.
- Further research into centrally acting sympathoinhibitory drugs for CHF management is warranted due to the prognostic importance of sympathetic activation.
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 microg and 100 microg 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 microg 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.