Differential effect of acute baroreceptor unloading on cardiac and systemic sympathetic tone in congestive heart failure

Alfred Baker Medical Unit, Baker Medical Research Institute, Melbourne, Australia. david.kaye@baker.edu.au

OBJECTIVES: The present study was designed to identify the hemodynamic factor or factors that reflexly contribute to activation of the cardiac sympathetic nerves in patients with severe congestive heart failure (CHF). BACKGROUND: We and others have previously shown that activation of the sympathetic nervous system is a key feature of CHF in humans. Furthermore, the degree of sympathetic activation shows marked regional heterogeneity and is most pronounced in the heart. Recent studies have shown a significant positive relation between pulmonary artery pressure and the magnitude of cardiac sympathetic activation. Of particular importance, the degree of cardiac sympathoexcitation has also been shown to be strongly associated with mortality in CHF. METHODS: We assessed total systemic and cardiac sympathetic activity (norepinephrine [NE] spillover method) in nine patients with severe CHF and significantly elevated pulmonary artery pressure (mean [+/-SEM] pulmonary artery pressure 46 +/- 3 mm Hg) at rest and during a titrated infusion of sodium nitroprusside (SNP). RESULTS: SNP infusion significantly reduced mean arterial blood pressure, pulmonary artery pressure and pulmonary capillary wedge pressure. During SNP infusion, the total body NE spillover rate (NESR) increased (from 7.9 +/- 1.7 to 11.2 +/- 3.1 nmol/min, p < 0.01), whereas the cardiac NESR decreased (from 522 +/- 86 to 409 +/- 71 pmol/min, p < 0.05). The ratio of cardiac/total NE spillover was also substantially reduced (from 7.8 +/- 1.3 to 4.9 +/- 0.9%, p < 0.001). CONCLUSIONS: There is a directionally opposite change in whole-body (increase) and cardiac (reduction) sympathetic nervous activity during SNP infusion, most likely due to unloading of arterial baroreceptors and specific cardiopulmonary baroreceptors, respectively, in severe CHF. These observations support the concept of a positive feedback relation between pulmonary artery pressure/filling pressure and cardiac sympathetic tone in CHF and serve to reinforce the importance of vasodilator therapy in this condition.

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