Whether the systemic sympathetic nervous system is activated as a compensatory mechanism in response to mitral regurgitation (MR) in humans is unknown. We tested the hypotheses that the systemic sympathetic nervous system would be activated in patients with MR in comparison with control subjects and that this activation would occur early in the disease process as a compensatory mechanism for chronic left ventricular (LV) volume overload.

We studied 37 patients with MR who underwent right heart catheterization and biplane cineventriculography to obtain LV end-diastolic and end-systolic volumes, ejection fractions, and regurgitant volumes. In these 37 patients with MR and in 23 control subjects, an [³H]-norepinephrine ([³H]-NE) infusion and multiple arterial blood samples provided data for a 2-compartment modeling analysis to calculate extravascular NE release rates (NE₂).

The mean NE₂ (2.05 ± 0.76 μg/min/m²) in the patients with MR was greater than that in the control subjects (1.48 ± 0.75 μg/min/m², P = .007). Furthermore, the mean NE₂ values were also greater in the patients with MR who were in clinical class I (P = .05), with a pulmonary capillary wedge pressure <12 mm Hg (P = .05) or a LV ejection fraction ≥0.60 (P = .06) compared with the control subjects. The mean NE₂ values were increased further in patients with MR who had a LV ejection fraction <0.60 (P = .02).

The systemic sympathetic nervous system is activated in patients with MR in comparison with control subjects, and this activation appears to occur early in the disease process as a compensatory mechanism for LV volume overload.