Abstract
Activation of the sympathetic nervous system is associated with increased mortality in congestive heart failure (CHF), and inhibition of the sympathetic nervous system by centrally acting sympatholytic agents has been shown to have beneficial effects on hemodynamics in these patients. However, the effect of sympathetic inhibition on survival in CHF is not clear. In the present study, the effect of sympathetic inhibition with clonidine on survival was examined in a rat model of heart failure. Myocardial infarction and heart failure was induced in rats by ligation of the left coronary artery and sham-operated rats served as the control. Two weeks after surgery, the ligated rats were randomly assigned to the clonidine (100 μg kg −1 d −1, n=30) group or the placebo (vehicle, n=31) group. All rats were followed daily for a 1-year period or until spontaneous death. Compared with placebo therapy, clonidine treatment reduced systolic blood pressure and heart rate throughout the experimental period. The plasma norepinephrine level determined at the end of the experiment was also reduced. Long-term sympathetic inhibition with clonidine treatment improved 1-year survival (50% vs. 22.6%, P<0.05) after surgery in this rat model of CHF.
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